StemCell Therapy

Triplet therapies have become the accepted standard of care in multiple myeloma, according toMarc J. Braunstein, MD, PhD, who added that emerging quadruplet therapies are also generating excitement in the field.

As seen in the up-front setting, there has been an explosion of therapies, not just for patients with relapsed/refractory multiple myeloma who progress after induction therapy, but also for patients who progress after multiple lines of therapy, said Braunstein, an assistant professor in the Department of Medicine at NYU Long Island School of Medicine. In the field, we appreciate that clonal resistance is truly what leads to shorter remission over time. Now that we have more therapies to offer, we are seeing several new combinations.

In a special episode of OncLiveOn Air, Braunstein, who is also the course co-director of the Hematology-Oncology System and co-director of the Autologous Stem Cell Transplant Program at NYU Winthrop Hospital of NYU Langone Healths Perlmutter Cancer Center, highlighted pivotal research on the use of triplet and quadruplet regimens in the up-front and relapsed/refractory settings presented during the 2020 ASCO Virtual Scientific Program.

VRd Remains the Standard of Care in Newly Diagnosed Multiple Myeloma

Carfilzomib (Kyprolis), lenalidomide (Revlimid), and dexamethasone (KRd) did not improve progression-free survival (PFS) in patients with newly diagnosed multiple myeloma, according to results of the phase 3 ENDURANCE (E1A11) trial (NCT01863550).1

In the randomized analysis, investigators compared the use of KRd with that of bortezomib (Velcade), lenalidomide, and dexamethasone (VRd) in treatment-nave patients with multiple myeloma who had an ECOG performance score of 0, 1, or 2. Patients also had to have acceptable hematological parameters and organ function and measurable disease in serum, urine, or bone marrow to be included. If they had grade 2 or higher peripheral neuropathy or New York Heart Association III or IV heart failure or myocardial infarction less than 6 months before study start, they could not participate.

The first co-primary end point of the trial was PFS for the induction randomization and the second co-primary end point was overall survival (OS) for the second randomization. Key secondary end points included overall response rate, minimal residual disease negativity rate per flow cytometry, time to progression, OS, and toxicity.

In the field, this trial was patiently awaited for some time because we were eager to see the head-to-head comparison of a triplet regimen that includes either the protostome inhibitor bortezomib or carfilzomib in combination with lenalidomide and dexamethasone, the 2 most common up-front regimens in the space, explained Braunstein.

A total of 1087 patients were randomized 1:1 to receive VRd (n = 542) or KRd (n = 545). Patients on the VRd arm received 1.3 mg/m2of bortezomib on days 1, 4, 8, and 11 for cycles 1-8 and the same dose on days 1 and 8 for cycles 9-12; 25 mg of daily lenalidomide on days 1-14; and 20 mg of dexamethasone in on days 1, 2, 4, 5, 8, 9, 11, and 12 for cycles 1-4, and then 10 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 for cycles 5-8, followed by 10 mg on days 1, 2, 8, and 9 for cycles 9-12. Treatment cycles were repeated every 3 weeks for 12 cycles.

Patients on the KRd arm received 20 mg/m2of carfilzomib on days 1 and 2 and 36 mg/m2on days 8, 9, 15, and 16 of cycle 1 followed by 36 mg/m2on days 1, 2, 8, 9, 15, and 16 for cycles 2-9; 25 mg of lenalidomide on days 1-21, and 40 mg of dexamethasone on days 1, 8, 15, and 22 for cycles 1-4 and 20 mg on days 1, 8, 15, and 22 for cycles 5-12. This treatment cycle was repeated every 4 weeks for 9 total cycles.

Results showed a median PFS of 34.4 months (95% CI, 30.1not evaluable) in the VRd arm compared with 34.6 months (95% CI, 28.8-37.8) in the KRd arm (HR, 1.04; 95% CI, 0.83-1.31; P = .742). In addition, on the VRd arm, 21 patients (4.0%) experienced a stringent complete response (sCR), 57 (10.8%) achieved a CR, 263 had a very good partial response (VGPR), and 103 patients had a partial response (PR). On the KRd arm, 31 patients (5.9%) achieved a sCR, 65 (12.4%) had a CR, 292 patients (55.5%) experienced a VGPR, and 68 (12.9%) had a PR. The median OS from induction randomization was not yet reached in either arm.

Moreover, treatment-related adverse effects (TRAEs) were mostly grade 3-5 and consisted of peripheral neuropathy, dyspnea, hypertension, heart failure, and acute kidney injury. The TRAEs of interest were cardiac, pulmonary, and renal, as well as peripheral neuropathy.

One of the criticisms of this study is that it did not include patients with high-risk multiple myeloma who, in prior studies, showed a benefit with carfilzomib, Braunstein noted. Notably, approximately 27% of patients in each group went on to receive autologous stem cell transplant, which was not planned according to the design of the study.

Based on these data, the investigators concluded that VRd should remain the standard of care.

Isatuximab/KRd for Newly Diagnosed, High-Risk Multiple Myeloma

Isatuximab-irfc (Sarclisa) plus KRd can be safely administered in patients with high-risk multiple myeloma, inducing deep responses, according to results from the interim analysis of the GMMG-concept trial presented during the meeting; this was the first study to investigate the quadruplet regimen in this patient population.2

In the multicenter, open-label, phase 2 analysis, investigators evaluated the efficacy of isatuximab, an anti-CD38 monoclonal antibody, in combination with KRd in patients with high-risk, newly diagnosed multiple myeloma. Patients could have received up to 1 cycle of anti-myeloma treatment prior to inclusion. They had to show acceptable organ function in order to participate.

The primary end point of the trial was minimal residual disease (MRD) negativity by flow cytometry to a sensitivity of 10-5and the secondary end point was PFS. Tertiary end points included ORR, duration of MRD negativity, OS, and quality-of-life (QOL) assessment.

This was an investigator-initiated study that ultimately evaluated a quadruplet regimen, which is the trend that we are pursuing these days in terms of up-front therapy, noted Braunstein.

In the analysis, 153 patients were randomized 1:1 based on transplant eligibility. In arm A, 117 transplant-eligible patients received 6 cycles of isatuximab plus KRd induction, 4 cycles of isatuximab plus KRd consolidation, and isatuximab plus KR maintenance. In arm B, 36 transplant-ineligible patients received the same course of treatment with 2 additional cycles of isatuximab plus KRd induction.

The interim analysis reported on a total of 50 patients: 46 in arm A and 4 in arm B. Results showed an ORR of 100% with the quadruplet, a VGPR or greater of 90%, a CR/sCR of 46%. In arm A, 41 of 46 patients achieved a VGPR or greater, while all patients in arm B achieved a VGPR. MRD was assessed in a total of 33 patients in arm A during induction and results showed that 20 patients were MRD negative, 11 were MRD positive, and 2 were not evaluable.

With regard to safety, the most common hematologic treatment-emergent AEs (TEAEs) reported were grade 3 or 4 and consisted of leukopenia (26%), neutropenia (34%), lymphopenia (28%), anemia (10%), and thrombocytopenia (14%).

Any-grade nonhematologic TEAEs included upper-respiratory tract infections (18%), pyrexia (12%), rash (16%), peripheral sensory neuropathy (16%), nasopharyngitis (10%), hypertension (12%), cardiac failure (4%), and infusion reaction (32%). No deaths were reported on the study.

We now have doublet, triplet, and quadruplet up-front regimens for patients with newly diagnosed multiple myeloma, Braunstein said. The more agents you combine synergistically to target the plasma cell clones, the deeper response rates you can achieve and that consistently correlates with longer remissions.

Belantamab Mafodotin Triplet for Relapsed/Refractory Multiple Myeloma

Belantamab mafodotin in combination with bortezomib and dexamethasone (B-Vd) demonstratedan acceptable safety profile, according to preliminary findings from a cohort of the phase 1/2 DREAMM-6 trial also presented during the meeting.3

In the 2-part, open-label, phase 1/2 study, investigators evaluated the safety and efficacy of the addition of belantamab mafodotin to B-Vd, 2 standard-of-care doublet regimens, in patients with relapsed/refractory multiple myeloma who have previously received at least 1 line of therapy. To be eligible for the trial, patients had to have measurable disease, acceptable organ function, and an ECOG performance status of 0 to 2. Those who underwent previous autologous stem cell transplant and those who were not candidates for transplant were permitted, along with those who were refractory to bortezomib.

The primary end points of the trial were safety, tolerability, and ORR as defined by the International Myeloma Working Group Uniform Response Criteria. Key secondary end points included preliminary clinical activity, further safety/tolerability examination, pharmacokinetic assessments, and the health-related QOL impact of the combination.

In arm A, belantamab mafodotin was combined with lenalidomide and dexamethasone (B-Rd) and, in arm B, belantamab mafodotin was combined with B-Vd.Part 1 was a dose-escalation phase and part 2 is an ongoing dose-expansion phase for each of the arms with either single (day 1) or split dosing (day 1 and 8) for belantamab mafodotin at 2.5 mg/kg or 3.4 mg/kg.

Results on 18 patients who received the 2.5-mg/kg dose of B-Vd experienced an ORR of 78% (95% CI, 52.4%-93.6%). In addition, patients demonstrated a clinical benefit rate of 83% (95% CI, 58.6%-96.4%) and the VGPR was 50%. The duration of response with the combination had not yet been reached.

Moreover, 89% of patients experienced grade 3 or 4 AEs. Dose reductions were required in 72% of patients because of AEs and all patients experienced a dose interruption or delay due to keratopathy and/or thrombocytopenia. Notably, all toxicities were found to be clinically manageable.

I believe belantamab mafodotin offers a unique therapeutic approach, which is very much needed in [patients with] refractory multiple myeloma, Braunstein concluded.

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Braunstein Reflects on the Rise of Quadruplet Therapies in Multiple Myeloma - OncLive

Basel, 8 September 2020 - Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced U.S. Food and Drug Administration (FDA) 510k clearance for the cobas BKV Test on the cobas 6800 and 8800 Systems. The test was previously granted FDA Breakthrough Device designation demonstrating the improved treatment or diagnosis of life-threatening diseases or conditions for transplant patients. The test provides standardised, high-quality results that can help healthcare professionals better assess the risk of complications caused by the BK virus in transplant patients and identify effective treatment options.

BK virus (BKV) is a member of the polyomavirus family that can cause severe transplant-associated complications. Infection can occur without symptoms and happen early in life. After primary infection, the virus can remain inactive, only to possibly reactivate in immunocompromised individuals such as transplant recipients.

Our diagnostic tests can help clinicians greatly improve patient treatment plans and make quick adjustments for personalised healthcare, said Thomas Schinecker, CEO Roche Diagnostics. This FDA clearance allows Roche to offer healthcare professionals a transplant testing portfolio that includes Cytomegalovirus, Epstein-Barr virus and BK virus so they can simultaneously monitor and improve care for transplant patients who are at risk for these common infections or viral reactivations which can cause further illness or death.

The cobas BKV Test is a polymerase chain reaction (PCR) viral load test that runs on the fully automated and widely available cobas 6800 and cobas 8800 Systems. Along with the previously approved cobas EBV and CMV Tests, the cobas BKV Test has been calibrated to the World Health Organization (WHO) International Standard. This means that test results are reported in international units, making it possible for laboratories anywhere in the U.S. to obtain comparable results when measuring levels of BKV DNA.

About the cobas BKV TestThe cobas BKV Test was previously granted Breakthrough Device Designation by the FDA, together with the cobas EBV Test.

The cobas BKV Test is a real-time polymerase chain reaction (PCR) test with dual-target technology that provides quantitative accuracy and guards against the risk of sequence variations that may be present in the BK virus. The cobas BKV Test has robust coverage with a limit of detection of 21.5 IU/mL and an expanded linear range from 21.5 IU/mL to 1E+08 IU/mL in EDTA plasma.

The test offers an alternative to lab-developed tests (LDTs) or Analyte Specific Reagent (ASR) combinations, potentially minimising variability and complexity in testing, reducing workload and alleviating risk for laboratories. The test supports the goal of result standardisation across institutions by providing reproducible, high-quality results for clinical decision-making.

The fully automated cobas BKV Test and the cobas CMV and cobas EBV Tests can run on the cobas 6800/8800 Systems simultaneously, providing absolute automation with proven performance and flexibility, leading to time savings and increased efficiency.

About BK polyomavirus BK polyomavirus (BKV) is a member of the polyomavirus family that can cause transplant-associated complications including nephropathy in kidney transplantation and hemorrhagic cystitis in hematopoietic stem cell transplantation. Infection can occur early in life, often with no symptoms. After primary infection, the virus can remain inactive throughout life, only to possibly reactivate in immunocompromised individuals, such as patients who receive solid-organ transplants. For kidney transplant patients, BKV infection is considered the most common viral complication, causing polyomavirus nephropathy (PVN) in up to 10 percent of kidney transplant recipients, and about 50 percent of PVN-affected patients will experience transplant graft failure.1 BKV is also associated with hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation.2

About the cobas 6800/8800 SystemsWhen every moment matters, the fully automated cobas 6800/8800 Systems offer the fastest time to results with the highest throughput and the longest walk-away time available among automated molecular platforms. The systems provide up to 96 results in about three hours and 384 results for the cobas 6800 System and 1,056 results for the cobas 8800 System in an eight hour shift.*

Both systems make it possible for labs to perform up to three tests in the same run with no pre-sorting required. The systems also enable up to eight hours (cobas 6800 System) and four hours (cobas 8800 System) of walk-away time with minimal user interaction.*

These real-time PCR systems serve the areas of infectious disease, donor screening, sexual health, transplant, respiratory and antimicrobial stewardship.

Through an ever-increasing worldwide install base of cobas 6800/8800 Systems, labs are quickly and easily processing millions of tests per month to meet the changing demands of their communities, their customers, and the patients relying on the results of each assay. Globally, labs know and trust that a Roche assay guarantees high precision, accuracy, and traceability to World Health Organization standards.

Today, rapid advancements in healthcare technology, a shortage of skilled workers, industry-wide consolidation, and the proven need to be ready for the next outbreak have health systems looking to lay a reliable foundation for the future. With proven performance, absolute automation, and unmatched flexibility delivering unparalleled throughput 24/7cobas 6800/8800 Systems are designed to ensure a labs long-term sustainability and success now, more than ever.

Learn more now: http://www.cobas68008800.com or http://diagnostics.roche.com.*May vary based on workflow demands

About RocheRoche is a global pioneer in pharmaceuticals and diagnostics focused on advancing science to improve peoples lives. The combined strengths of pharmaceuticals and diagnostics under one roof have made Roche the leader in personalised healthcare a strategy that aims to fit the right treatment to each patient in the best way possible.

Roche is the worlds largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and diseases of the central nervous system. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management.

Founded in 1896, Roche continues to search for better ways to prevent, diagnose and treat diseases and make a sustainable contribution to society. The company also aims to improve patient access to medical innovations by working with all relevant stakeholders. More than thirty medicines developed by Roche are included in the World Health Organization Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and cancer medicines. Moreover, for the eleventh consecutive year, Roche has been recognised as one of the most sustainable companies in the Pharmaceuticals Industry by the Dow Jones Sustainability Indices (DJSI).

The Roche Group, headquartered in Basel, Switzerland, is active in over 100 countries and in 2019 employed about 98,000 people worldwide. In 2019, Roche invested CHF 11.7 billion in R&D and posted sales of CHF 61.5 billion. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit http://www.roche.com.

All trademarks used or mentioned in this release are protected by law.

References[1] Jamboti, J. S. (2016) BK virus nephropathy in renal transplant recipients. Nephrology, 21: 647 654. doi: 10.1111/nep.12728. [2] Hirsch HH, Randhawa PS; AST Infectious Diseases Community of Practice. BK polyomavirus in solid organ transplantation-Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019;33(9):e13528. doi:10.1111/ctr.13528

Roche Group Media RelationsPhone: +41 61 688 8888 / e-mail: media.relations@roche.com

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Roche receives FDA clearance for BK virus quantitative test on cobas 6800/8800 Systems to support better care for transplant patients - GlobeNewswire

Weekly Reports | Aug 10 2020

By Tim Boreham, Editor, The New Criterion

The ASX biotechs surfing the COVID-19 story

Normally investors shun speculative plays in times of market uncertainties, but thats not been the case with ASX-listed life sciences stocks across the drug, diagnostics and device sectors.

Naturally, the biotechs drawing a connection with fighting or detecting the virus spurious or otherwise have seen their valuations soar. Not that investor interest is limited to the Covid cluster, with capital raisings in the sector supported across the board.

A notable winner valuation-wise is Genetic Signatures ((GSS)), which markets molecular diagnostics tests for bacterial and viral conditions including superbugs, sexually transmitted diseases and norovirus (the number one plague of cruise ships before the coronavirus hopped on board).

Sold under the Easyscreen brand, the kits allow for rapid and accurate detection in large volumes. The tests take the genetic information of the targeted organism and change the genetic sequence to reduce the number of variables.

And, yes, the company is a COVID-19 story as well. Before the plague descended, the companys Easyscreen tests had not been able to distinguish Sars-cov-2 from say, Severe Acute Respiratory Syndrome (SARS), but the company has devised a variant to do just that.

Reporting a 278% revenue surge to $4.7m for the June quarter, management called out demand for the COVID-19 tests as a growth driver.

Broker Bell Potter notes the global molecular diagnostics market was worth more than $US6bn in 2018 and is expected to grow to $US10bn by 2026.

The sectors also been a hotbed of acquisitions, such as Thermo Fishers recently-lobbed $US11.5bn offer for Dutch diagnostic group Qiagen and Danaher Corps $US4bn acquisition of US counterpart Cepheid in 2018.

We expect merger and acquisition activity to continue in the space and Genetic Signatures is strategically well positioned to attract interest as it further expands into key US and European markets and grows is product suite, Bell Potter says.

While Genetic Signatures is a case of building incremental revenues, stem cell developer Mesoblast ((MSB)) is on the cusp of company-moving announcements pertaining to several late-stage clinical trials and expected US approval of its therapy for graft versus host disease (a common affliction for transplant patients).

Naturally, most investors are focused on the COVID-19 trial which involves treating critical-care patients with its off the shelf therapy remestemcel-L (branded Ryoncil).

Most coronavirus victims die from acute respiratory distress syndrome (ARDS), an inflammatory condition caused by the immune systems response to the virus.

Mesoblast aimed to enrol 300 patients across 30 US hospitals a moving target given the disease epicentre is moving from region to region.

Nonetheless, the first patients were dosed in May, with an interim analysis is due when at least 30% of the patients have been treated for 30 days.

In other words, investors should soon know whether the company is on the cusp of a major treatment breakthrough.

And if thats not enough excitement, Mesoblast expects to announce results from two phase III studies: a 566-patient effort for chronic heart failure and a 404-patient trial for chronic lower back pain caused by disc degeneration.

Also in the stem-cell space, Cynata Therapeutics ((CYP)) is planning to carry out its own COVID-19 clinical trials not just in relation to ARDS, but sepsis and cytokine release syndrome (all causes of COVID-19 deaths).

The company is encouraged by pre-clinical modelling and has regulatory approval to carry out a trial.

The company planned to enrol 24 intensive care patients in NSW but perhaps it should refocus efforts south of the Murray.

It was fairly clear that Australias prevention measures effectively flattened the curve and we quickly ran out of available patients, Cynata chief Ross Macdonald said before the Victorian resurgence.

Tackling the cause of COVID-19 mortalities is one thing, but what if the risk of contracting the diseases could be more accurately predicted beyond the clinical factors of age and co-morbidities such as heart disease and diabetes?

That way, the denizens of locked down geographies such as Victoria could discard their masks and emerge from isolation.

Meanwhile, shares in kidney disease house Dimerix ((DXB)) last week soared on positive clinical results pertaining to a rare condition called focal segmental glomerusclerosis (FSGS).

But the drug candidate in question, DMX-200 has also been selected for appraisal in a global trial to treat ARDS, the common element between ARDS and FSGS being fibrosis.

Known in shorthand as REMAP-CAP, the World Health Organisation endorsed trial aims to enrol 7000 patients across more than 200 sites. DMX-200 is one of many potential therapies being looked at, but the beauty for Dimerix is the trial costs are paid the governments that are funding REMAP-CAP.

Changing tack, molecular diagnostics house Genetic Technologies ((GTG)) has filed a provisional patent for a genetics-based assessment of the risk of developing COVID-19.

Based on third-party genomic data from 1500 COVID-19 patients, the company intends to develop a prototype model to identify patients most likely to require hospitalisation should they contract the disease.

If and when a vaccine materialises, the genetic profiling could help to prioritise who gets jabbed first.

Hitherto known for its predictive breast cancer kits, Genetic Technologies has never matched its performance to its promises.

But US investors have been willing to support the stock, with the company raising $US5.1m in a placement via its Nasdaq listing.

Disclaimer: Under no circumstances have there been any inducements or like made by the company mentioned to either IIR or the author. The views here are independent and have no nexus to IIRs core research offering. The views here are not recommendations and should not be considered as general advice in terms of stock recommendations in the ordinary sense.

Content included in this article is not by association the view of FNArena (see our disclaimer).

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Merck (NYSE: MRK), known as MSD outside the United States and Canada, and Eisai today announced that the U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) regarding Merck’s and Eisai’s applications seeking accelerated approval of KEYTRUDA, Merck’s anti-PD-1 therapy, plus LENVIMA, the orally available multiple receptor tyrosine kinase inhibitor discovered by Eisai, for the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC). The applications were based on data from the Phase 1b KEYNOTE-524/Study 116 trial, which showed clinically meaningful efficacy in the single-arm setting. These data were recently presented at the 2020 American Society of Clinical Oncology Annual Meeting and supported a Breakthrough Therapy designation granted by the FDA in July 2019. Ahead of the Prescription Drug User Fee Act (PDUFA) action dates of Merck’s and Eisai’s applications, another combination therapy was approved based on a randomized, controlled trial that demonstrated overall survival. Consequently, the CRL stated that Merck’s and Eisai’s applications do not provide evidence that KEYTRUDA in combination with LENVIMA represents a meaningful advantage over available therapies for the treatment of unresectable or metastatic HCC with no prior systemic therapy for advanced disease. Since the applications for KEYNOTE-524/Study 116 no longer meet the criteria for accelerated approval, both companies plan to work with the FDA to take appropriate next steps, which include conducting a well-controlled clinical trial that demonstrates substantial evidence of effectiveness and the clinical benefit of the combination. As such, LEAP-002, the Phase 3 trial evaluating the KEYTRUDA plus LENVIMA combination as a first-line treatment for advanced HCC, is currently underway and fully enrolled. The CRL does not impact the current approved indications for KEYTRUDA or for LENVIMA.

This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20200708005239/en/

Merck and Eisai are continuing to evaluate the KEYTRUDA plus LENVIMA combination across 13 different tumor types in 18 clinical trials, including the LEAP (LEnvatinib And Pembrolizumab) clinical program.

About KEYTRUDA® (pembrolizumab) Injection, 100 mg

KEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,200 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

Selected KEYTRUDA® (pembrolizumab) Indications

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.

KEYTRUDA is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection.

Non-Small Cell Lung Cancer

KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) 1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is stage III where patients are not candidates for surgical resection or definitive chemoradiation, or metastatic.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS 1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

Small Cell Lung Cancer

KEYTRUDA is indicated for the treatment of patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy and at least 1 other prior line of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Head and Neck Squamous Cell Cancer

KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [combined positive score (CPS) 1] as determined by an FDA-approved test.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy.

Classical Hodgkin Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory classical Hodgkin lymphoma (cHL), or who have relapsed after 3 or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Primary Mediastinal Large B-Cell Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.

Urothelial Carcinoma

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 [combined positive score (CPS) 10], as determined by an FDA-approved test, or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

KEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.

Microsatellite Instability-High or Mismatch Repair Deficient Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR)

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.

Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer

KEYTRUDA is indicated for the first-line treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC).

Gastric Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Esophageal Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1 (CPS 10) as determined by an FDA-approved test, with disease progression after one or more prior lines of systemic therapy.

Cervical Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Hepatocellular Carcinoma

KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Merkel Cell Carcinoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Renal Cell Carcinoma

KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

Endometrial Carcinoma

KEYTRUDA, in combination with LENVIMA, is indicated for the treatment of patients with advanced endometrial carcinoma that is not MSI-H or dMMR, who have disease progression following prior systemic therapy and are not candidates for curative surgery or radiation. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trial.

Tumor Mutational Burden-High

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.

Cutaneous Squamous Cell Carcinoma

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) that is not curable by surgery or radiation.

Selected Important Safety Information for KEYTRUDA

Immune-Mediated Pneumonitis

KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases. Pneumonitis occurred in 3.4% (94/2799) of patients with various cancers receiving KEYTRUDA, including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%). Pneumonitis occurred in 8.2% (65/790) of NSCLC patients receiving KEYTRUDA as a single agent, including Grades 3-4 in 3.2% of patients, and occurred more frequently in patients with a history of prior thoracic radiation (17%) compared to those without (7.7%). Pneumonitis occurred in 6% (18/300) of HNSCC patients receiving KEYTRUDA as a single agent, including Grades 3-5 in 1.6% of patients, and occurred in 5.4% (15/276) of patients receiving KEYTRUDA in combination with platinum and FU as first-line therapy for advanced disease, including Grades 3-5 in 1.5% of patients.

Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.

Immune-Mediated Colitis

KEYTRUDA can cause immune-mediated colitis. Colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 2 (0.4%), 3 (1.1%), and 4 (<0.1%). Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.

Immune-Mediated Hepatitis (KEYTRUDA) and Hepatotoxicity (KEYTRUDA in Combination With Axitinib)

Immune-Mediated Hepatitis

KEYTRUDA can cause immune-mediated hepatitis. Hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.4%), and 4 (<0.1%). Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.

Hepatotoxicity in Combination With Axitinib

KEYTRUDA in combination with axitinib can cause hepatic toxicity with higher than expected frequencies of Grades 3 and 4 ALT and AST elevations compared to KEYTRUDA alone. With the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased ALT (20%) and increased AST (13%) were seen. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider more frequent monitoring of liver enzymes as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt KEYTRUDA and axitinib, and consider administering corticosteroids as needed.

Immune-Mediated Endocrinopathies

KEYTRUDA can cause adrenal insufficiency (primary and secondary), hypophysitis, thyroid disorders, and type 1 diabetes mellitus. Adrenal insufficiency occurred in 0.8% (22/2799) of patients, including Grade 2 (0.3%), 3 (0.3%), and 4 (<0.1%). Hypophysitis occurred in 0.6% (17/2799) of patients, including Grade 2 (0.2%), 3 (0.3%), and 4 (<0.1%). Hypothyroidism occurred in 8.5% (237/2799) of patients, including Grade 2 (6.2%) and 3 (0.1%). The incidence of new or worsening hypothyroidism was higher in 1185 patients with HNSCC (16%) receiving KEYTRUDA, as a single agent or in combination with platinum and FU, including Grade 3 (0.3%) hypothyroidism. Hyperthyroidism occurred in 3.4% (96/2799) of patients, including Grade 2 (0.8%) and 3 (0.1%), and thyroiditis occurred in 0.6% (16/2799) of patients, including Grade 2 (0.3%). Type 1 diabetes mellitus, including diabetic ketoacidosis, occurred in 0.2% (6/2799) of patients.

Monitor patients for signs and symptoms of adrenal insufficiency, hypophysitis (including hypopituitarism), thyroid function (prior to and periodically during treatment), and hyperglycemia. For adrenal insufficiency or hypophysitis, administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA for Grade 2 adrenal insufficiency or hypophysitis and withhold or discontinue KEYTRUDA for Grade 3 or Grade 4 adrenal insufficiency or hypophysitis. Administer hormone replacement for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and administer antihyperglycemics in patients with severe hyperglycemia.

Immune-Mediated Nephritis and Renal Dysfunction

KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.1%), and 4 (<0.1%) nephritis. Nephritis occurred in 1.7% (7/405) of patients receiving KEYTRUDA in combination with pemetrexed and platinum chemotherapy. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue for Grade 3 or 4 nephritis.

Immune-Mediated Skin Reactions

Immune-mediated rashes, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) (some cases with fatal outcome), exfoliative dermatitis, and bullous pemphigoid, can occur. Monitor patients for suspected severe skin reactions and based on the severity of the adverse reaction, withhold or permanently discontinue KEYTRUDA and administer corticosteroids. For signs or symptoms of SJS or TEN, withhold KEYTRUDA and refer the patient for specialized care for assessment and treatment. If SJS or TEN is confirmed, permanently discontinue KEYTRUDA.

Other Immune-Mediated Adverse Reactions

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue in patients receiving KEYTRUDA and may also occur after discontinuation of treatment. For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA and administer corticosteroids. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. Resume KEYTRUDA when the adverse reaction remains at Grade 1 or less following corticosteroid taper. Permanently discontinue KEYTRUDA for any Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.

The following clinically significant immune-mediated adverse reactions occurred in less than 1% (unless otherwise indicated) of 2799 patients: arthritis (1.5%), uveitis, myositis, Guillain-Barr syndrome, myasthenia gravis, vasculitis, pancreatitis, hemolytic anemia, sarcoidosis, and encephalitis. In addition, myelitis and myocarditis were reported in other clinical trials, including classical Hodgkin lymphoma, and postmarketing use.

Treatment with KEYTRUDA may increase the risk of rejection in solid organ transplant recipients. Consider the benefit of treatment vs the risk of possible organ rejection in these patients.

Infusion-Related Reactions

KEYTRUDA can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, which have been reported in 0.2% (6/2799) of patients. Monitor patients for signs and symptoms of infusion-related reactions. For Grade 3 or 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Immune-mediated complications, including fatal events, occurred in patients who underwent allogeneic HSCT after treatment with KEYTRUDA. Of 23 patients with cHL who proceeded to allogeneic HSCT after KEYTRUDA, 6 (26%) developed graft-versus-host disease (GVHD) (1 fatal case) and 2 (9%) developed severe hepatic veno-occlusive disease (VOD) after reduced-intensity conditioning (1 fatal case). Cases of fatal hyperacute GVHD after allogeneic HSCT have also been reported in patients with lymphoma who received a PD-1 receptorblocking antibody before transplantation. Follow patients closely for early evidence of transplant-related complications such as hyperacute graft-versus-host disease (GVHD), Grade 3 to 4 acute GVHD, steroid-requiring febrile syndrome, hepatic veno-occlusive disease (VOD), and other immune-mediated adverse reactions.

In patients with a history of allogeneic HSCT, acute GVHD (including fatal GVHD) has been reported after treatment with KEYTRUDA. Patients who experienced GVHD after their transplant procedure may be at increased risk for GVHD after KEYTRUDA. Consider the benefit of KEYTRUDA vs the risk of GVHD in these patients.

Increased Mortality in Patients With Multiple Myeloma

In trials in patients with multiple myeloma, the addition of KEYTRUDA to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of these patients with a PD-1 or PD-L1 blocking antibody in this combination is not recommended outside of controlled trials.

Embryofetal Toxicity

Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. Advise women of this potential risk. In females of reproductive potential, verify pregnancy status prior to initiating KEYTRUDA and advise them to use effective contraception during treatment and for 4 months after the last dose.

Adverse Reactions

In KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9% of 555 patients with advanced melanoma; adverse reactions leading to permanent discontinuation in more than one patient were colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). The most common adverse reactions (20%) with KEYTRUDA were fatigue (28%), diarrhea (26%), rash (24%), and nausea (21%).

In KEYNOTE-002, KEYTRUDA was permanently discontinued due to adverse reactions in 12% of 357 patients with advanced melanoma; the most common (1%) were general physical health deterioration (1%), asthenia (1%), dyspnea (1%), pneumonitis (1%), and generalized edema (1%). The most common adverse reactions were fatigue (43%), pruritus (28%), rash (24%), constipation (22%), nausea (22%), diarrhea (20%), and decreased appetite (20%).

In KEYNOTE-054, KEYTRUDA was permanently discontinued due to adverse reactions in 14% of 509 patients; the most common (1%) were pneumonitis (1.4%), colitis (1.2%), and diarrhea (1%). Serious adverse reactions occurred in 25% of patients receiving KEYTRUDA. The most common adverse reaction (20%) with KEYTRUDA was diarrhea (28%).

In KEYNOTE-189, when KEYTRUDA was administered with pemetrexed and platinum chemotherapy in metastatic nonsquamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 20% of 405 patients. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonitis (3%) and acute kidney injury (2%). The most common adverse reactions (20%) with KEYTRUDA were nausea (56%), fatigue (56%), constipation (35%), diarrhea (31%), decreased appetite (28%), rash (25%), vomiting (24%), cough (21%), dyspnea (21%), and pyrexia (20%).

In KEYNOTE-407, when KEYTRUDA was administered with carboplatin and either paclitaxel or paclitaxel protein-bound in metastatic squamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 15% of 101 patients. The most frequent serious adverse reactions reported in at least 2% of patients were febrile neutropenia, pneumonia, and urinary tract infection. Adverse reactions observed in KEYNOTE-407 were similar to those observed in KEYNOTE-189 with the exception that increased incidences of alopecia (47% vs 36%) and peripheral neuropathy (31% vs 25%) were observed in the KEYTRUDA and chemotherapy arm compared to the placebo and chemotherapy arm in KEYNOTE-407.

In KEYNOTE-042, KEYTRUDA was discontinued due to adverse reactions in 19% of 636 patients with advanced NSCLC; the most common were pneumonitis (3%), death due to unknown cause (1.6%), and pneumonia (1.4%). The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia (7%), pneumonitis (3.9%), pulmonary embolism (2.4%), and pleural effusion (2.2%). The most common adverse reaction (20%) was fatigue (25%).

In KEYNOTE-010, KEYTRUDA monotherapy was discontinued due to adverse reactions in 8% of 682 patients with metastatic NSCLC; the most common was pneumonitis (1.8%). The most common adverse reactions (20%) were decreased appetite (25%), fatigue (25%), dyspnea (23%), and nausea (20%).

Adverse reactions occurring in patients with SCLC were similar to those occurring in patients with other solid tumors who received KEYTRUDA as a single agent.

In KEYNOTE-048, KEYTRUDA monotherapy was discontinued due to adverse events in 12% of 300 patients with HNSCC; the most common adverse reactions leading to permanent discontinuation were sepsis (1.7%) and pneumonia (1.3%). The most common adverse reactions (20%) were fatigue (33%), constipation (20%), and rash (20%).

In KEYNOTE-048, when KEYTRUDA was administered in combination with platinum (cisplatin or carboplatin) and FU chemotherapy, KEYTRUDA was discontinued due to adverse reactions in 16% of 276 patients with HNSCC. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonia (2.5%), pneumonitis (1.8%), and septic shock (1.4%). The most common adverse reactions (20%) were nausea (51%), fatigue (49%), constipation (37%), vomiting (32%), mucosal inflammation (31%), diarrhea (29%), decreased appetite (29%), stomatitis (26%), and cough (22%).

In KEYNOTE-012, KEYTRUDA was discontinued due to adverse reactions in 17% of 192 patients with HNSCC. Serious adverse reactions occurred in 45% of patients. The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. The most common adverse reactions (20%) were fatigue, decreased appetite, and dyspnea. Adverse reactions occurring in patients with HNSCC were generally similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy, with the exception of increased incidences of facial edema and new or worsening hypothyroidism.

In KEYNOTE-087, KEYTRUDA was discontinued due to adverse reactions in 5% of 210 patients with cHL. Serious adverse reactions occurred in 16% of patients; those 1% included pneumonia, pneumonitis, pyrexia, dyspnea, GVHD, and herpes zoster. Two patients died from causes other than disease progression; 1 from GVHD after subsequent allogeneic HSCT and 1 from septic shock. The most common adverse reactions (20%) were fatigue (26%), pyrexia (24%), cough (24%), musculoskeletal pain (21%), diarrhea (20%), and rash (20%).

In KEYNOTE-170, KEYTRUDA was discontinued due to adverse reactions in 8% of 53 patients with PMBCL. Serious adverse reactions occurred in 26% of patients and included arrhythmia (4%), cardiac tamponade (2%), myocardial infarction (2%), pericardial effusion (2%), and pericarditis (2%). Six (11%) patients died within 30 days of start of treatment. The most common adverse reactions (20%) were musculoskeletal pain (30%), upper respiratory tract infection and pyrexia (28% each), cough (26%), fatigue (23%), and dyspnea (21%).

In KEYNOTE-052, KEYTRUDA was discontinued due to adverse reactions in 11% of 370 patients with locally advanced or metastatic urothelial carcinoma. Serious adverse reactions occurred in 42% of patients; those 2% were urinary tract infection, hematuria, acute kidney injury, pneumonia, and urosepsis. The most common adverse reactions (20%) were fatigue (38%), musculoskeletal pain (24%), decreased appetite (22%), constipation (21%), rash (21%), and diarrhea (20%).

In KEYNOTE-045, KEYTRUDA was discontinued due to adverse reactions in 8% of 266 patients with locally advanced or metastatic urothelial carcinoma. The most common adverse reaction resulting in permanent discontinuation of KEYTRUDA was pneumonitis (1.9%). Serious adverse reactions occurred in 39% of KEYTRUDA-treated patients; those 2% were urinary tract infection, pneumonia, anemia, and pneumonitis. The most common adverse reactions (20%) in patients who received KEYTRUDA were fatigue (38%), musculoskeletal pain (32%), pruritus (23%), decreased appetite (21%), nausea (21%), and rash (20%).

In KEYNOTE-057, KEYTRUDA was discontinued due to adverse reactions in 11% of 148 patients with high-risk NMIBC. The most common adverse reaction resulting in permanent discontinuation of KEYTRUDA was pneumonitis (1.4%). Serious adverse reactions occurred in 28% of patients; those 2% were pneumonia (3%), cardiac ischemia (2%), colitis (2%), pulmonary embolism (2%), sepsis (2%), and urinary tract infection (2%). The most common adverse reactions (20%) were fatigue (29%), diarrhea (24%), and rash (24%).

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Merck and Eisai Receive Complete Response Letter for KEYTRUDA (pembrolizumab) plus LENVIMA (lenvatinib) Combination as First-Line Treatment for...

BOSTON & LOUISVILLE, Ky.--(BUSINESS WIRE)--Talaris Therapeutics, Inc., a privately held biotechnology company developing transformative cell therapies that have the potential to induce durable immune tolerance across a range of indications, announced that the U.S. Food and Drug Administration (FDA) has approved the companys Investigational New Drug (IND) application for the evaluation of Talaris novel cell therapy FCR001 in the treatment of diffuse systemic sclerosis (SSc), a severe form of the rare autoimmune disease scleroderma. Approval of this IND allows Talaris to initiate a Phase 1/2a trial at sites across the U.S., including Duke University and the University of Michigan.

Were very eager to study the tolerogenic potential of FCR001 for patients with severe autoimmune disease, said Scott Requadt, Chief Executive Officer of Talaris. Individuals with diffuse cutaneous systemic sclerosis, a subset of scleroderma with high morbidity and mortality, are in great need of safe and effective, disease-modifying, treatment options. We believe FCR001 could represent an important new approach to treating this serious condition.

Scleroderma, which derives from the Greek words sclero, meaning hard, and derma, meaning skin, is a rare and potentially fatal chronic autoimmune disease which causes progressive scarring, or fibrosis, of the bodys connective tissues. Scleroderma can either be localized or systemic. Systemic scleroderma, also called systemic sclerosis (SSc), is further divided into the limited cutaneous subset and the diffuse cutaneous subset, depending on the degree of skin involvement. Both types affect the skin and vital internal organs, especially the lungs, kidneys, gut and heart, resulting in organ dysfunction. Patients with the diffuse subset generally have rapidly progressive skin and internal organ involvement and have worse outcomes than the limited subtype.

Based on encouraging data from randomized clinical trials, autologous hematopoietic stem cell transplant (HSCT) is increasingly used to treat severe cases of diffuse cutaneous SSc, where it has been shown to halt organ damage and induce clinical remission. However, because patients are transplanted with their own stem cells, there is a risk of disease recurrence, and patients typically must first undergo full myeloablative conditioning with or without total body irradiation, which is associated with direct organ toxicity and increased risk of future cancers.

Talaris allogeneic cell therapy, FCR001, is a novel, one-time treatment intended to induce immune tolerance in the recipient and which can be used across all levels of donor-recipient HLA mismatch. Treatment with FCR001 is preceded by non-myeloablative conditioning. In a Phase 2 clinical trial in de novo living donor kidney transplant recipients, FCR001 resulted in durable immune tolerance in 70% of the 37 recipients treated; these individuals were able to successfully discontinue their anti-rejection medications and no tolerized patient has had to resume immunosuppression (median follow-up of over 5 years, longest follow-up is over 10 years). Furthermore, seven of the successfully tolerized patients had kidney failure due to an underlying autoimmune disease, and none of these patients has experienced recurrence of their underlying autoimmune disease post-treatment. Based on these encouraging data and its broad therapeutic potential in autoimmune disease, FCR001 will be evaluated in a planned Phase 1/2a trial of patients with diffuse cutaneous SSc.

A safe, allogeneic stem cell transplant treatment using nonmyeloablative conditioning could offer important additional benefits over current autologous HSCT as a treatment for this severe form of systemic sclerosis, said Keith Michael Sullivan, M.D., Professor of Medicine at Duke University Medical School.

The diffuse cutaneous systemic sclerosis subset I see in my practice have very limited treatment options. Autologous stem cell transplant has demonstrated the potential to induce durable remissions in randomized clinical trials, but involves significant risks to the patients, said Dinesh Khanna, M.D., M.Sc., Director of the Scleroderma Program and Professor of Medicine at the University of Michigan Medical School. I am excited to participate in this clinical trial of FCR001, and hopeful that it could result in a safer and more durably effective treatment for these patients.

About FCR001

FCR001 is an investigational, allogeneic cell therapy developed by Talaris Therapeutics to induce or restore patients immune tolerance. FCR001 builds on over 30 years of research by the companys founder, Dr. Suzanne Ildstad, into the means by which durable immune tolerance can be induced in a patient who receives a transplanted organ or can be restored in patients with certain immune-mediated or blood disorders. FCR001 has received both Orphan Drug Designation and Regenerative Medicine Advanced Therapy (RMAT) designation from the U.S. Food and Drug Administration. A Phase 3 trial of FCR001 in living donor kidney transplant recipients, FREEDOM-1, is now enrolling patients; more information can be found at: http://freedom1study.com/

About Talaris Therapeutics

Talaris Therapeutics, Inc. is a late-clinical stage biotechnology company that is developing transformative cell therapies with the potential to eliminate the burden of chronic immunosuppression for organ transplant recipients as well as induce durable remissions in patients with severe auto-immune and immune-mediated disorders. Talaris was founded on technology discovered and developed by Dr. Suzanne Ildstad and operates its own cell processing facility in Louisville, KY. Talaris is backed by leading life sciences investors Blackstone Life Sciences, Longitude Capital and Qiming Venture Partners USA and maintains corporate offices in Boston, MA and Louisville, KY. http://www.TalarisTx.com.

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FDA Approves Talaris Therapeutics' IND for Its Allogeneic Cell Therapy FCR001 to Be Evaluated in Patients With a Severe Form of Scleroderma - Business...

LIVINGSTON, NJ Federal officials have released a list of businesses across the nation, including in Livingston, which were approved for loans under the Paycheck Protection Program (PPP).

More than 4.9 million loans worth roughly $521 billion have been approved for businesses and nonprofit organizations across the United States under the program, which was established by the Coronavirus Aid, Relief, and Economic Security Act (CARES Act).

See a list of awardees in Livingston below.

The aid is meant to help small businesses keep workers on their payrolls during the COVID-19 crisis. Funds can also be used to pay interest on mortgages, rent, and utilities. PPP loans have an interest rate of one percent and can be fully forgiven under certain conditions. (Learn more about the program)

Roughly 22,000 entities in New Jersey were approved for loans greater than $150,000. Awards in the Garden State also included loans to higher education institutions, private schools, manufacturers, car washes, real estate agent companies and nonprofits.

Earlier this week, the U.S. Small Business Administration (SBA) and U.S. Treasury released a list of loan recipients by town, adding a big caveat about the data:

Several companies that made the list have since questioned its accuracy, claiming that they didn't apply for or receive the funds the government says they did, CNBC reported.

See a list of approved loans over $150,000 in Livingston via the searchable database below. Enter the town's name where it says "Search business name of town" to begin.

More here:
Coronavirus PPP Loans In Livingston: Where The Money Went - Livingston, NJ Patch

Kidney failure (or renal failure) is a condition in which the kidneys fail to function properly. Physiologically, renal failure is described as a decrease in blood filtration (glomerular filtration rate or GFR). Clinically, this is manifested in elevated serum creatinine. Still not well understood are many of the factors that are involved in kidney failure. Researchers are studying the effects of nutritional proteins and the concentration of cholesterol in the blood.

Acute renal failure: Some kidney problems happen quickly, such as from an accident that causes kidney damage. A great loss of blood can cause sudden kidney failure, also some drugs or poisons can cause the kidneys to stop working. Such sudden drops in kidney function are called acute renal failure.Are you living with Kidney Failure? Call us today for a FREE consultation for stem cell therapy or fill out the Case Evaluation Form to begin.ProgenCells stem cell procedures are scientifically designed and professionally followed; we have one goal in mind: substantial health improvement of people with simple logistics.

We do not suggest that patients substitute their current medical doctor or abandon current treatments. Since this is a long-term protocol, is necessary that your current medical doctor continues to follow up on your case.

Information: Our medical experts study your case, your current condition as well as your health history. After a full evaluation it is decided if you could be eligible to participate in this protocol, and receive cell therapy. A multidisciplinary medical committee studies your case and honestly considers your improvement potential.

After your case is evaluated, a ProgenCell staff member will contact you regarding your particular case and potential benefits. We also answer any question you may have about the procedure or the requirements to make it happen.

Plan: Once you have consented, we can plan ahead. Because of ProgenCells high demand, it is necessary to schedule a date for your procedure at least 2 to 3 weeks in advance. Exceptions can be made when the condition of the patient requires urgent care.

Conditioning and medical procedure: When your appointment is scheduled, we will assign you an agent that will become your personal assistant related to your medical procedure. This assistant will be able to help you with administrative tasks, logistics, planning your stay, communication with the medical staff, etc. Your personal agent will provide you the proper documentation to complete your medical records and will explain the informed consent. In short, we will coordinate all thats necessary for a practical and easy stay with ProgenCell. The complete treatment from beginning to end- will take from 3 to 6 hours, depending on the case. During your recovery time you will have access to a telephone, TV and internet.Call us today for a FREE consultation or fill out the Case Evaluation Form to begin cell therapy.

Acute renal failure (ARF) is, as its name implies, a rapidly progressive loss of renal function, generally characterized by oliguria, a decreased urine production (measured as less than 400 mL per day for adults, less than 0.5 mL/kg/hour in children, or less than 1 mL/kg/hour in infants), and water imbalance of body fluids and electrolyte disorders.

Chronic renal failure (CRF) is the condition that is caused by permanent and irreversible damage to kidney function, secondary to any cause. Worldwide, the most common causes (but not the only) of chronic kidney disease include diabetes, hypertension, and obstructive diseases of the urinary tract (such as stones, tumors, etc.). It can arise from the complication of a large number of kidney diseases such as IgA nephropathy (Berger disease), inflammatory diseases of the kidney (collectively called glomerulonephritis), chronic pyelonephritis and urinary retention, and the use of toxic drugs to the kidney (particularly contrast media and some antibiotics). Terminal renal failure is the ultimate result, which usually requires dialysis until a donor can be found for a kidney transplant.

If the disease is detected early, the speed with which the damage progresses can be slowed, delaying the onset of replacement therapies and giving the patient more time to prepare for such therapy. Currently available renal replacement therapies are hemodialysis, peritoneal dialysis, and renal transplantation.

Causes of Kidney FailureIn the United States, about 80,000 people are diagnosed with kidney failure each year. This is a serious condition. Diabetes is the most common cause of kidney failure and constitutes more than forty percent of new cases. Even when drugs and diet can control diabetes, the disease can lead to nephropathy and kidney failure. There are about sixteen million diabetics in the United States and of those, about 100,000 suffer from kidney failure due to diabetes.People with kidney failure must undergo dialysis in either of two modes or transplantation to receive a kidney from a healthy donor. Blacks, American Indians, and the descendants of Hispanic Americans have diabetes, kidney disease, and renal failure in a proportion higher than the general population. Scientists have been unable to explain this phenomenon and cannot explain fully the interplay of factors leading to diabetic nephropathy. These factors include heredity, diet, and other conditions such as hypertension.

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Stem Cell Therapy For Kidney Failure. Learn More Now ...

Are you at risk for anemia?

Take our short quiz to learn more about the symptoms of anemia.

There's more to chronic kidney disease than you think...

If your kidneys are not working properly, they may not be able to help your body make the red blood cells it needs. Anemia is a common side effect of kidney disease.

Anemia happens when there are not enough red blood cells in your body.

Red blood cells carry oxygen through your bloodstream, giving you energy and helping your muscles, bones, and organs work properly.

The oxygen that we breathe in passes through our lungs and into the red blood cells.

In anemia, there are not enough red blood cells to carry this oxygen around the body.

Anemia can make you feel weak and tired because you are not getting the energy you need.

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Anybody can develop anemia, but it is very common in people with CKD. People with CKD may start to have anemia in the early stages of CKD, and anemia usually gets worse as CKD gets worse. If your kidneys are not working as well as they should, you are more likely to get anemia.

Anemia in CKD is more common if you:

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Anemia can happen with or without symptoms. Many of the symptoms of anemia can also be caused by other problems. The only way be sure if you have anemia is to get tested. If you are experiencing symptoms, it is important that you talk to your doctor.

Feeling dizzy or having difficulty concentrating may be a sign that your brain is not getting enough oxygen.

Paleness is caused by reduced blood flow or a lower number of red blood cells.

Anemia in CKD can increase your risk of heart problems because the heart has to work harder to provide blood to your body. If you experience an unusually fast heart rate or are worried about your heart health, please speak to your doctor.

Your blood may not have enough red blood cells to deliver oxygen to your muscles. By increasing your breathing rate, your body is trying to bring more oxygen into your body.

Easy fatigue, loss of energy, and reduced physical capacity

Sensitivity to the cold may mean there is not enough oxygen being delivered in the blood to your body

Take our short quiz to learn more about the symptoms of anemia.

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There are two main causes of anemia in CKD:

All of the cells in your body live for a certain amount of time and then die. Your body is always working to make new cells to replace the ones that have died. Red blood cells live for about 115 days. Your kidneys help your body make red blood cells.

Healthy kidneys make a hormone called erythropoietin (EPO). EPO sends a signal to the body to make more red blood cells. If your kidneys are not working as well as they should, they cant make enough EPO. Without enough EPO, your body doesnt know to make enough red blood cells. This means fewer red blood cells are available for carrying oxygen through your body.

Iron is a mineral found in many foods, such as meats and leafy greens. Your body uses iron to make red blood cells. A common cause of anemia in people with CKD is iron deficiency. Iron deficiency means you do not have enough iron in your body. It can be caused by not getting enough iron in your diet or by losing blood, either through blood tests or during dialysis. If you dont take in enough iron through your diet, you can get anemia. Around half of people with CKD stages 2 to 5 have some kind of iron deficiency.

There are several kinds of anemia. Anemia caused by having too little EPO or too little iron in your body are the most common in people with CKD. Talk to your doctor to learn more.

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Talk to your doctor if you think you may have anemia. The only way to know if you have anemia is to have a blood test. When you have kidney disease, your doctor will want you to have blood tests often. These tests are used to check not only your kidney function, but also for signs of any other problems, such as the number of red blood cells and how much iron you have in your body.

The test for anemia is a simple blood test to check for the amount of hemoglobin in your blood. Hemoglobin is a part of your red blood cells. Figuring out the amount of hemoglobin you have in your blood can tell your doctor how many red blood cells you have.

Your doctor may also ask you if youve noticed any symptoms, such as changes in skin color or feeling unusually tired.

Take our short quiz to learn more about the symptoms of anemia.

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Getting your anemia treated can help you feel better. Depending on the cause of your anemia, your doctor may recommend one of the following treatments:

Doctors and researchers are working on potential new treatments for anemia. New treatments in development are tested in clinical trials. If youre interested in joining a clinical trial to try an investigational new treatment for anemia, visit ClinicalTrials.gov to learn about all available clinical trials for anemia.

If you have CKD, getting early treatment for your anemia can help slow the progress of your CKD. If you think you might have anemia, talk to your doctor about getting tested.

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Anemia and end-stage renal disease (ESRD), also known as kidney failure, often go hand in hand. Most people with kidney failure who are on dialysis have anemia. Kidney transplant patients are also at higher risk for anemia. Learn more.

Click here to download a copy of the Anemia in ESRD booklet.

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Talk with your doctor or another member of your health care team to find out more about your anemia symptoms and treatment options. Our Talk to Your Doctor Guide can help you get the conversation started.

Note: This survey is not a medical diagnosis. This guide is an awareness tool designed for you and your doctor to use together. The information you provide is anonymous and will not shared.

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Anemia in chronic kidney disease - kidneyfund.org

The worlds biggest listed pure-play stem cell developer has a busy slate of clinical work, notably in therapies for advanced heart failure, chronic back pain and graft-versus-host disease (GvHD).

Now these programs are approaching a thrilling denouement and, as the Demtel man enthused, theres more: Mesoblast (ASX:MSB) is also undertaking an expanded coronavirus trial after a 12-patient effort showed promising results in treating acute respiratory distress syndrome (Ards), the usual cause of death with COVID-19.

The patients received infusions of Mesoblasts allogeneic (off the shelf) mesenchymal stem cell candidate, remestemcel-L, acquired from Osiris for $106m in 2013.

Meanwhile, results from two phase III trials are expected this (September) quarter: a 566-patient effort for chronic heart failure and a 404-patient trial for chronic lower back pain caused by disc degeneration.

And in September, the US Food and Drug Administration will rule on whether or not the company can market its GvHD therapy on American shores.

Mesoblast founder and CEO Prof Silviu Itescu notes that across all its therapies the company is targeting the most severe cases where alternative therapies dont exist.

Mesoblasts proprietary process selects precursor and stem cells from the bone marrow of healthy adults, creating a master cell bank. This cell kitty is then expanded into thousands of doses for off-the-shelf use, without the need for tissue matching.

Mesoblast is targeting a common market across all its disease indications: inflammation. In the case of heart disease, tissue macrophages (cells) churn out inflammatory factors that damage heart muscle and cause fibrosis and vascular dysfunction.

The stem cells respond to severe inflammation by switching the culprit macrophages off and converting them to nice cells that actually protect the heart muscle.

This is the central mechanism in each of our disease states: heart failure, back pain, GvHD and rheumatoid arthritis, Professor Itescu says. We have the potential to make a big difference in some very big disease states where inflammation is central.

Backed by the Pratt familys listed investment vehicle Thorney Investments, Mesoblast debuted on the ASX in 2004 and reached a peak valuation of $2.5bn in 2011 before suffering a reality check.

Culprits included a phase II heart trial that failed to meet primary endpoints, a badly executed Nasdaq listing and Israel pharma house Teva Pharmaceuticals decision to walk away from a heart program partnership in 2016.

Mesoblast dual listed on the Nasdaq in November 2015, accompanied by a $US63m capital raising.

The companys Ards and GvHD programs are based on mesenchymal stem cell assets acquired from US pharma group Osiris Therapeutics in October 2013.

Mesoblasts own-developed cells are called mesenchymal precursor cells and they are being developed for rheumatoid arthritis and diabetic nephropathy, as well as the aforementioned heart failure and lower back pain programs.

Ards is bought on by an excessive immune response to the virus in the lungs. The immune cells produce inflammatory cytokines, which destroy lung tissue and can also damage the liver, kidney and heart.

Remestemcell-L has the potential to tame the cytokine storm in Ards and may offer a life-saving treatment for those unfortunate individual sufferers of COVID-19 Ards, Professor Itescu says.

Mesoblasts COVID-19 proclamations have been coming so thick and fast that its been Ard(s) just to keep up. But the core excitement cluster was around Mesoblasts April 23 disclosure of the results of the trial at New Yorks Mt Sinai Hospital, covering moderate to acute Ards cases.

Under the compassionate use protocol, the patients were treated with two infusions of remestemcel-L over the first five days.

The results? Nine of the 12 patients came off a ventilator within a median 10 days, with 83 per cent survival (the Grim Reapers spin on this is that two of them died).

In comparison, only 9 per cent of patients at one reference hospital (38 out of 445 patients) were able to come off the ventilator with standard-of-care treatment.

Another US hospital reported that only 38 patients of 320 or 12 per cent survived.

Of course, 12 people good and true are adequate numbers for a jury, but sub-optimal to comprise a statistically significant trial.

Thus, the company is enrolling 300 patients in a phase III, randomised, controlled trial of severe Ards patients at 30 sites.

The first patients were dosed in early May, with about 15 sites established as the company chases the disease from the northeast to the southern states.

Mesoblast chief medical officer Professor Fred Grossman says the company is carefully choosing hot spots such as Alabama which, as of late May had the no vacancy signs outside its intensive care wards.

The sites are recruiting quite quickly, he says. There is a tremendous interest in this study.

The trial leaders will undertake an interim analysis at 30 days, and when 30 per cent of patients have reached their primary endpoint. At that point the trial can be dumped on futility grounds, or expanded to the control group because it appears to be working.

Remestemcell-L has investigational new drug (IND) status with the US Food and Drug Administration, meaning the company swiftly can initiate trials on patients with very dismal prospects.

Long-suffering Mesoblast investors will recall that the companys shares tumbled 28 per cent in November 2018 after a 159-patient trial of Rexlemestrocel-L (Revascor) for end-stage heart failure did not meet its primary endpoint of weaning patients from left ventricle assist devices (LVADs or heart pumps).

The company claimed the endpoint was set by the independent !!! investigators and was of little real clinical interest. What really mattered was that the trial showed reduced gastrointestinal bleeding by 76 per cent and hospitalisations by 65 per cent.

Investors are now nervously awaiting the first readout of the broader 566-patient chronic heart failure trial across 59 US sites.

Mesoblast targeted patients with class three or four disease, the sickest 15 to 20 per cent of patients who have failed standard-of-care drugs.

Class three patients have a 20 per cent chance of dying within two years while with class four its a case of flip a coin that you will be around in 12 months.

At this stage, Mesoblast retains its heart treatment rights except in China, where it is partnered with Tasly Pharmaceutical.

Mesoblasts phase III back pain trial aimed to enroll 404 patients with lower back pain caused by degenerative disc disease.

The endpoint of the trial, dubbed MPC-06-ID, is an improvement in pain and function over 24 months.

As with the heart trial, results are imminent and its a toss-up as to what release will hit the ASX announcements feed first.

The company is liaising with its global back pain partner Grunenthal GmbH about the clinical protocol for a European phase III confirmatory trial.

In Japan, Mesoblast is partnered with JCR Pharmaceutical for its approved GvHD treatment called Temcell and its off and racing in that smallish but enthusiastic market.

Meanwhile, the company is angling to enter the US market for a similar GvHD treatment, branded Ryoncil.

GvHD afflicts about half of the 30,000 patients annually undergoing allogeneic bone marrow transplant, typically for blood cancers, with their bodies rejecting the alien transplant.

In March, the FDA granted priority review with a September 30 action date, but we might have a good idea of the outcome in August.

Why? Because thats when the FDAs relevant advisory committee meets to vote on the matter and the (virtual) gathering is open to the public.

A date is yet to be set. While advisory committee views are not binding on the FDA, they usually presage the final decision.

If approved, Mesoblast could be selling Ryoncil in the US by the time were carving the Christmas turkey (badly, in the case of your columnist).

Buoyed by the COVID-19 results, Mesoblast in May wasted no time tapping institutional investors for an idle $US90m ($129.6m) in a placement.

Mesoblast already had a healthy cash balance of $US60m.

The raising was struck at $3.20 a share, a modest 7 per cent discount to the prevailing price.

The funds, in the main, will be used to scale-up manufacturing of remestemcell-L and to support the phase III trial, as well as for working capital and general corporate purposes.

The company also has $US67m available through existing financing facilities and partnerships.

Mesoblast reported revenue of $US31.45m for the nine months to March 2020, up 113 per cent. The reported loss narrowed 34 per cent to $US45.3m, reflecting curtailed research and development spend by $US7.5m, or 15 per cent.

The revenue included $US5.9m of JCR royalties from Temcell sales in Japan and milestone revenue of $US25m.

The company stands to pocket up to $US150m of royalties and milestones from Grunenthal prior to any European launch of Revascor.

Successful sales could result in up to $US1bn in milestone payments.

Over the last decade, Mesoblasts ASX shares have traded as high as $9 (October 2011) and as low as $1.03 (December last year).

To the Meso-sceptics the company has promised far too much with limited commercial success, while raising $1bn since listing 16 years ago.

Dare we say that Mesoblast now looks more focused and to be getting somewhere?

When we last covered Mesoblast in March 2019, Professor Itescu said he was 95 per cent certain the company would do what no other Aussie biotech in phase III had done: win FDA drug approval.

Well, Clinuvel has stolen that Aussie first honour, but Mesoblast is well placed to get over the line with a GvHD treatment in the US, which presents a market eight times the size of Japans.

Its certainly rare for a biotech to expect results for three major trials and a key regulatory decision in the space of months.

If the heart and back pain results are definitively positive and the FDA green lights GvHD, the company hits the jackpot. If two or more of them bomb lets not go there.

Your ultra conservative columnist regards the COVID-19 stuff as the icing on the cake with an outside chance of success, especially given the hundreds of other programs in the coronavirus-busting sector.

Disclosure: Dr Boreham is not a qualified medical practitioner and does not possess a doctorate of any sort. But he hopes to become proficient in turkey carving by December 25.

This column first appeared in Biotech Daily.

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Dr Borehams Crucible: Mesoblast within months of 3 major trial results, key regulatory decision - Stockhead

KENILWORTH, N.J.--(BUSINESS WIRE)--Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that the U.S. Food and Drug Administration (FDA) has approved KEYTRUDA, Mercks anti-PD-1 therapy, as monotherapy for the first-line treatment of patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer. The approval is based on results from the Phase 3 KEYNOTE-177 trial, in which KEYTRUDA significantly reduced the risk of disease progression or death by 40% (HR=0.60 [95% CI, 0.45-0.80; p=0.0004]) compared with chemotherapy, the current standard of care. In the study, treatment with KEYTRUDA also more than doubled median progression-free survival (PFS) compared with chemotherapy (16.5 months [95% CI, 5.4-32.4] versus 8.2 months [95% CI, 6.1-10.2]).

Todays approval has the potential to change the treatment paradigm for the first-line treatment of patients with MSI-H colorectal cancer, based on the important findings from KEYNOTE-177 that showed KEYTRUDA monotherapy demonstrated superior progression-free survival compared to standard of care chemotherapy, said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. Our commitment to pursuing biomarker research continues to help us bring new treatments to patients, particularly for those who have few available options.

Immune-mediated adverse reactions, which may be severe or fatal, can occur with KEYTRUDA, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and renal dysfunction, severe skin reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation (HSCT). Based on the severity of the adverse reaction, KEYTRUDA should be withheld or discontinued and corticosteroids administered if appropriate. KEYTRUDA can also cause severe or life-threatening infusion-related reactions. Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. For more information, see Selected Important Safety Information below.

This approval was granted less than one month following the submission of a new supplemental Biologics License Application (sBLA), which was reviewed under the FDAs Real-Time Oncology Review (RTOR) pilot program. This review also was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence that provides a framework for concurrent submission and review of oncology drugs among its international partners. For this application, a modified Project Orbis was undertaken, and the FDA is collaborating with the Australian Therapeutic Goods Administration, Health Canada and Swissmedic on their ongoing review of the application.

Patients with unresectable or metastatic MSI-H colorectal cancer have historically faced poor outcomes, and until today, chemotherapy-containing regimens were the only FDA-approved first-line treatment options, said Luis A. Diaz, M.D., head of the division of Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center. In patients who were treated with KEYTRUDA and responded (n=67) in the KEYNOTE-177 trial, 43% of patients experienced a duration of response lasting two years or longer. This approval helps address the unmet need to provide a new monotherapy treatment option for patients.

Data Supporting the Approval

The approval was based on data from KEYNOTE-177 (NCT02563002), a multi-center, randomized, open-label, active-controlled trial that enrolled 307 patients with previously untreated unresectable or metastatic MSI-H or dMMR colorectal cancer. Microsatellite instability (MSI) or mismatch repair (MMR) tumor status was determined locally using polymerase chain reaction or immunohistochemistry, respectively. Patients with autoimmune disease or a medical condition that required immunosuppression were ineligible.

Patients were randomized 1:1 to receive KEYTRUDA 200 mg intravenously every three weeks or investigators choice of the following chemotherapy regimens given intravenously every two weeks:

Treatment with KEYTRUDA or chemotherapy continued until Response Evaluation Criteria in Solid Tumors (RECIST) v1.1-defined progression of disease as determined by the investigator or unacceptable toxicity. Patients treated with KEYTRUDA without disease progression could be treated for up to 24 months. Assessment of tumor status was performed every nine weeks. Patients randomized to chemotherapy were offered KEYTRUDA at the time of disease progression. The main efficacy outcome measure was progression-free survival (PFS) as assessed by blinded independent central review (BICR) according to RECIST v1.1, modified to follow a maximum of 10 target lesions and a maximum of five target lesions per organ, and overall survival (OS). Additional efficacy outcome measures were objective response rate (ORR) and duration of response (DOR).

Patients were enrolled and randomized to KEYTRUDA (n=153) or chemotherapy (n=154). The baseline characteristics of these 307 patients were: median age of 63 years (range, 24 to 93), 47% age 65 or older; 50% male; 75% White and 16% Asian; 52% had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, and 48% had an ECOG PS of 1; and 27% received prior adjuvant or neoadjuvant chemotherapy. Among the 154 patients randomized to receive chemotherapy, 143 received chemotherapy per the protocol. Of these 143 patients, 56% received mFOLFOX6, 44% received FOLFIRI, 70% received bevacizumab plus mFOLFOX6 or FOLFIRI, and 11% received cetuximab plus mFOLFOX6 or FOLFIRI. The median follow-up time was 27.6 months (range, 0.2 to 48.3 months).

In this study, KEYTRUDA monotherapy significantly reduced the risk of disease progression or death by 40% (HR=0.60 [95% CI, 0.45-0.80; p=0.0004]) and showed a median PFS of 16.5 months (95% CI, 5.4-32.4) compared with 8.2 months (95% CI, 6.1-10.2) for patients treated with chemotherapy. For PFS, in the KEYTRUDA arm, there were 82 patients (54%) with an event versus 113 patients (73%) in the chemotherapy arm. At the time of the PFS analysis, the OS data were not mature (66% of the required number of events for the OS final analysis). For patients treated with KEYTRUDA, the ORR was 44% (95% CI, 35.8-52.0), with a complete response rate of 11% and a partial response rate of 33%, and for patients treated with chemotherapy, the ORR was 33% (95% CI, 25.8-41.1), with a complete response rate of 4% and a partial response rate of 29%. Median DOR was not reached (range, 2.3+ to 41.4+) with KEYTRUDA versus 10.6 months (range, 2.8 to 37.5+) with chemotherapy. Based on 67 patients with a response in the KEYTRUDA arm and 51 patients with a response in the chemotherapy arm, 75% in the KEYTRUDA arm had a duration of response greater than or equal to 12 months versus 37% in the chemotherapy arm, and 43% in the KEYTRUDA arm had a duration of response greater than or equal to 24 months versus 18% in the chemotherapy arm.

Among the 153 patients with MSI-H or dMMR colorectal cancer treated with KEYTRUDA, the median duration of exposure to KEYTRUDA was 11.1 months (range, 1 day to 30.6 months). Adverse reactions occurring in patients with MSI-H or dMMR colorectal cancer were similar to those occurring in 2,799 patients with melanoma or non-small cell lung cancer treated with KEYTRUDA as a single agent.

About KEYTRUDA (pembrolizumab) Injection, 100 mg

KEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of the bodys immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industrys largest immuno-oncology clinical research program. There are currently more than 1,200 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

Selected KEYTRUDA (pembrolizumab) Indications

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.

KEYTRUDA is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection.

Non-Small Cell Lung Cancer

KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) 1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is stage III where patients are not candidates for surgical resection or definitive chemoradiation, or metastatic.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS 1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

Small Cell Lung Cancer

KEYTRUDA is indicated for the treatment of patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy and at least 1 other prior line of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Head and Neck Squamous Cell Cancer

KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [combined positive score (CPS) 1] as determined by an FDA-approved test.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy.

Classical Hodgkin Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory classical Hodgkin lymphoma (cHL), or who have relapsed after 3 or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Primary Mediastinal Large B-Cell Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.

Urothelial Carcinoma

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 [combined positive score (CPS) 10], as determined by an FDA-approved test, or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

KEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.

Microsatellite Instability-High (MSI-H) Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR)

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.

Colorectal Cancer

KEYTRUDA is indicated for the first-line treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC).

Gastric Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Esophageal Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1 (CPS 10) as determined by an FDA-approved test, with disease progression after one or more prior lines of systemic therapy.

Cervical Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Hepatocellular Carcinoma

KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Merkel Cell Carcinoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Renal Cell Carcinoma

KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

Tumor Mutational Burden-High (TMB-H)

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.

Cutaneous Squamous Cell Carcinoma

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) that is not curable by surgery or radiation.

Selected Important Safety Information for KEYTRUDA

Immune-Mediated Pneumonitis

KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases. Pneumonitis occurred in 3.4% (94/2799) of patients with various cancers receiving KEYTRUDA, including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%). Pneumonitis occurred in 8.2% (65/790) of NSCLC patients receiving KEYTRUDA as a single agent, including Grades 3-4 in 3.2% of patients, and occurred more frequently in patients with a history of prior thoracic radiation (17%) compared to those without (7.7%). Pneumonitis occurred in 6% (18/300) of HNSCC patients receiving KEYTRUDA as a single agent, including Grades 3-5 in 1.6% of patients, and occurred in 5.4% (15/276) of patients receiving KEYTRUDA in combination with platinum and FU as first-line therapy for advanced disease, including Grades 3-5 in 1.5% of patients.

Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.

Immune-Mediated Colitis

KEYTRUDA can cause immune-mediated colitis. Colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 2 (0.4%), 3 (1.1%), and 4 (<0.1%). Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.

Immune-Mediated Hepatitis (KEYTRUDA) and Hepatotoxicity (KEYTRUDA in Combination With Axitinib)

Immune-Mediated Hepatitis

KEYTRUDA can cause immune-mediated hepatitis. Hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.4%), and 4 (<0.1%). Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.

Hepatotoxicity in Combination With Axitinib

KEYTRUDA in combination with axitinib can cause hepatic toxicity with higher than expected frequencies of Grades 3 and 4 ALT and AST elevations compared to KEYTRUDA alone. With the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased ALT (20%) and increased AST (13%) were seen. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider more frequent monitoring of liver enzymes as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt KEYTRUDA and axitinib, and consider administering corticosteroids as needed.

Immune-Mediated Endocrinopathies

KEYTRUDA can cause adrenal insufficiency (primary and secondary), hypophysitis, thyroid disorders, and type 1 diabetes mellitus. Adrenal insufficiency occurred in 0.8% (22/2799) of patients, including Grade 2 (0.3%), 3 (0.3%), and 4 (<0.1%). Hypophysitis occurred in 0.6% (17/2799) of patients, including Grade 2 (0.2%), 3 (0.3%), and 4 (<0.1%). Hypothyroidism occurred in 8.5% (237/2799) of patients, including Grade 2 (6.2%) and 3 (0.1%). The incidence of new or worsening hypothyroidism was higher in 1185 patients with HNSCC (16%) receiving KEYTRUDA, as a single agent or in combination with platinum and FU, including Grade 3 (0.3%) hypothyroidism. Hyperthyroidism occurred in 3.4% (96/2799) of patients, including Grade 2 (0.8%) and 3 (0.1%), and thyroiditis occurred in 0.6% (16/2799) of patients, including Grade 2 (0.3%). Type 1 diabetes mellitus, including diabetic ketoacidosis, occurred in 0.2% (6/2799) of patients.

Monitor patients for signs and symptoms of adrenal insufficiency, hypophysitis (including hypopituitarism), thyroid function (prior to and periodically during treatment), and hyperglycemia. For adrenal insufficiency or hypophysitis, administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA for Grade 2 adrenal insufficiency or hypophysitis and withhold or discontinue KEYTRUDA for Grade 3 or Grade 4 adrenal insufficiency or hypophysitis. Administer hormone replacement for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and administer antihyperglycemics in patients with severe hyperglycemia.

Immune-Mediated Nephritis and Renal Dysfunction

KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.1%), and 4 (<0.1%) nephritis. Nephritis occurred in 1.7% (7/405) of patients receiving KEYTRUDA in combination with pemetrexed and platinum chemotherapy. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue for Grade 3 or 4 nephritis.

Immune-Mediated Skin Reactions

Immune-mediated rashes, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) (some cases with fatal outcome), exfoliative dermatitis, and bullous pemphigoid, can occur. Monitor patients for suspected severe skin reactions and based on the severity of the adverse reaction, withhold or permanently discontinue KEYTRUDA and administer corticosteroids. For signs or symptoms of SJS or TEN, withhold KEYTRUDA and refer the patient for specialized care for assessment and treatment. If SJS or TEN is confirmed, permanently discontinue KEYTRUDA.

Other Immune-Mediated Adverse Reactions

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue in patients receiving KEYTRUDA and may also occur after discontinuation of treatment. For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA and administer corticosteroids. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. Resume KEYTRUDA when the adverse reaction remains at Grade 1 or less following corticosteroid taper. Permanently discontinue KEYTRUDA for any Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.

The following clinically significant immune-mediated adverse reactions occurred in less than 1% (unless otherwise indicated) of 2799 patients: arthritis (1.5%), uveitis, myositis, Guillain-Barr syndrome, myasthenia gravis, vasculitis, pancreatitis, hemolytic anemia, sarcoidosis, and encephalitis. In addition, myelitis and myocarditis were reported in other clinical trials, including classical Hodgkin lymphoma, and postmarketing use.

Treatment with KEYTRUDA may increase the risk of rejection in solid organ transplant recipients. Consider the benefit of treatment vs the risk of possible organ rejection in these patients.

Infusion-Related Reactions

KEYTRUDA can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, which have been reported in 0.2% (6/2799) of patients. Monitor patients for signs and symptoms of infusion-related reactions. For Grade 3 or 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Immune-mediated complications, including fatal events, occurred in patients who underwent allogeneic HSCT after treatment with KEYTRUDA. Of 23 patients with cHL who proceeded to allogeneic HSCT after KEYTRUDA, 6 (26%) developed graft-versus-host disease (GVHD) (1 fatal case) and 2 (9%) developed severe hepatic veno-occlusive disease (VOD) after reduced-intensity conditioning (1 fatal case). Cases of fatal hyperacute GVHD after allogeneic HSCT have also been reported in patients with lymphoma who received a PD-1 receptorblocking antibody before transplantation. Follow patients closely for early evidence of transplant-related complications such as hyperacute graft-versus-host disease (GVHD), Grade 3 to 4 acute GVHD, steroid-requiring febrile syndrome, hepatic veno-occlusive disease (VOD), and other immune-mediated adverse reactions.

In patients with a history of allogeneic HSCT, acute GVHD (including fatal GVHD) has been reported after treatment with KEYTRUDA. Patients who experienced GVHD after their transplant procedure may be at increased risk for GVHD after KEYTRUDA. Consider the benefit of KEYTRUDA vs the risk of GVHD in these patients.

Increased Mortality in Patients With Multiple Myeloma

In trials in patients with multiple myeloma, the addition of KEYTRUDA to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of these patients with a PD-1 or PD-L1 blocking antibody in this combination is not recommended outside of controlled trials.

Embryofetal Toxicity

Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. Advise women of this potential risk. In females of reproductive potential, verify pregnancy status prior to initiating KEYTRUDA and advise them to use effective contraception during treatment and for 4 months after the last dose.

Adverse Reactions

In KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9% of 555 patients with advanced melanoma; adverse reactions leading to permanent discontinuation in more than one patient were colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). The most common adverse reactions (20%) with KEYTRUDA were fatigue (28%), diarrhea (26%), rash (24%), and nausea (21%).

In KEYNOTE-002, KEYTRUDA was permanently discontinued due to adverse reactions in 12% of 357 patients with advanced melanoma; the most common (1%) were general physical health deterioration (1%), asthenia (1%), dyspnea (1%), pneumonitis (1%), and generalized edema (1%). The most common adverse reactions were fatigue (43%), pruritus (28%), rash (24%), constipation (22%), nausea (22%), diarrhea (20%), and decreased appetite (20%).

In KEYNOTE-054, KEYTRUDA was permanently discontinued due to adverse reactions in 14% of 509 patients; the most common (1%) were pneumonitis (1.4%), colitis (1.2%), and diarrhea (1%). Serious adverse reactions occurred in 25% of patients receiving KEYTRUDA. The most common adverse reaction (20%) with KEYTRUDA was diarrhea (28%).

In KEYNOTE-189, when KEYTRUDA was administered with pemetrexed and platinum chemotherapy in metastatic nonsquamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 20% of 405 patients. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonitis (3%) and acute kidney injury (2%). The most common adverse reactions (20%) with KEYTRUDA were nausea (56%), fatigue (56%), constipation (35%), diarrhea (31%), decreased appetite (28%), rash (25%), vomiting (24%), cough (21%), dyspnea (21%), and pyrexia (20%).

In KEYNOTE-407, when KEYTRUDA was administered with carboplatin and either paclitaxel or paclitaxel protein-bound in metastatic squamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 15% of 101 patients. The most frequent serious adverse reactions reported in at least 2% of patients were febrile neutropenia, pneumonia, and urinary tract infection. Adverse reactions observed in KEYNOTE-407 were similar to those observed in KEYNOTE-189 with the exception that increased incidences of alopecia (47% vs 36%) and peripheral neuropathy (31% vs 25%) were observed in the KEYTRUDA and chemotherapy arm compared to the placebo and chemotherapy arm in KEYNOTE-407.

In KEYNOTE-042, KEYTRUDA was discontinued due to adverse reactions in 19% of 636 patients with advanced NSCLC; the most common were pneumonitis (3%), death due to unknown cause (1.6%), and pneumonia (1.4%). The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia (7%), pneumonitis (3.9%), pulmonary embolism (2.4%), and pleural effusion (2.2%). The most common adverse reaction (20%) was fatigue (25%).

In KEYNOTE-010, KEYTRUDA monotherapy was discontinued due to adverse reactions in 8% of 682 patients with metastatic NSCLC; the most common was pneumonitis (1.8%). The most common adverse reactions (20%) were decreased appetite (25%), fatigue (25%), dyspnea (23%), and nausea (20%).

Adverse reactions occurring in patients with SCLC were similar to those occurring in patients with other solid tumors who received KEYTRUDA as a single agent.

In KEYNOTE-048, KEYTRUDA monotherapy was discontinued due to adverse events in 12% of 300 patients with HNSCC; the most common adverse reactions leading to permanent discontinuation were sepsis (1.7%) and pneumonia (1.3%). The most common adverse reactions (20%) were fatigue (33%), constipation (20%), and rash (20%).

Originally posted here:
FDA Approves Merck's KEYTRUDA (pembrolizumab) for First-Line Treatment of Patients With Unresectable or Metastatic MSI-H or dMMR Colorectal Cancer -...

Anti Aging Stem Cell Therapy in Mexico (888) 988-0515

SAN DIEGO (PRWEB) June 24, 2020

R3 Stem Cell International announced a new program offering stem cell therapy for anti aging in Mexico. The program offers several options with stem cell counts up to 200 million and pricing starting at $2950.

To date, R3 International has been offering stem cell therapy in Mexico successfully for many conditions including autism, COPD, kidney failure, liver disease, heart conditions, dementia, stroke, neuropathy and arthritis just to name a few. One of the main reasons the regenerative therapies work so well is due to the modulation of inflammation, which happens to be one of the key factors in the aging process.

Stem cell therapy for anti aging at R3 International is offered by experienced, licensed doctors who have performed hundreds of cases. There are 3 options for obtaining stem cell treatment in Mexico. The first involves a one time treatment of either 30 million or 50 million cells ($2950 or $3950). If desired, R3 also offers the option for 200 million cells over a 5 day period, or with several visits over a year (starts at $8975).

The treatments at R3 International involve stem cell biologics that have been extremely safe to date. The lab includes quality assurance standards that exceed those of the FDA in the US. Culturing of the umbilical cord stem cell material does not involve the need for preservative and is restricted below 5 generations. This means the stem cells are potent with viability exceeding 93%.

The process for receiving treatment starts with a free phone consultation with one of the licensed doctors. Then treatment is booked, and R3's patient concierge representatives work with each patient on travel logistics. Support is provided throughout the process.

For more information on stem cell therapy for anti aging and to obtain a free consultation, call (888) 988-0515 or visit https://stemcelltreatmentclinic.com to learn more.

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Originally posted here:
R3 International Offering Stem Cell Therapy Program for Anti Aging in Mexico - PR Web

GOLDEN, COLO / ACCESSWIRE / June 29, 2020 / Vitro Diagnostics, Inc. (OTCQB:VODG), dba Vitro Biopharma, announced its 2nd quarter ended April 30th 2020 financial results of operations.

Vitro Diagnostics Inc. ("Vitro Biopharma") announced a reduction in 2nd quarter revenues across all its revenue categories. Vitro Biopharma recorded 2nd quarter revenues of $128,631 vs $211,900 a decrease of 39% over the same comparative quarter last year. Prior to the lockdowns which began at different times for different jurisdictions Vitro had reported increasing revenues across all its revenue categories for 13 consecutive quarters. We expect to see revenue returning in the 4th quarter of 2020 and into the first half of 2021. Preliminary feedback from our customers indicates that patients awaiting treatments at our partner clinic in the Cayman Islands http://www.DVCstem.com are not dropping off but merely postponing their treatments and as such a backlog is building rather than customer cancellations. The cosmetic clinics http://www.Infinivive.com have started to open up but only with reduced occupancy and variations by state and hence reduced revenue into the 3rd quarter with expectations of a revival of revenue in the 4th quarter of 2020 and into the first half of 2021.

Overall operating expenses increased in the quarter by $114,178 to $281,485 from $167,307 in the prior year's comparative quarter. The increase in expenses reflects the increased costs of FDA regulatory, legal, consulting, business and product development expenses. The company added extra resources to turn its attention to the world wide challenge of finding therapies to fight the Covid-19. Vitro filed an Investigational New Drug ("IND") application and also received emergency use authorization from the FDA for use of AlloRx Stem Cells ® in the treatment of COVID-19 patients. A patient was treated subsequent to the end of the second quarter. There were no adverse events demonstrating safety and the patient showed evidence of efficacy including improved lung and kidney function. We also entered into an MOU with GIOSTAR, a leading global stem cell research operating multiple international stem cell clinics.

During and subsequent to the quarter the company achieved and pursed the following objectives:

During the quarter and subsequent to the quarter the company continued with its Series A Convertible Preferred Stock offering to accredited investors under the SEC Regulation D exemption. The preferred Stock is priced at $25 per share which is convertible at $0.25 cents per share for a total of 100 shares. The minimum investment is $50,000 per unit. The company sold $550,000 of the Series A Convertible Preferred Stock during and subsequent to the quarter. The offering was sold out at $1,000,000 and the company is considering expanding it to ensure sufficient working capital during the Coronavirus pandemic and to start the regulatory process of current reporting audits and funding for its expanded clinical trial activities with the FDA.

As a part of our overall strategy to target both global and US stem cell markets, Vitro submitted a Phase I IND application to the FDA https://vitrobiopharma.com/vitro-biopharma-submits-ind-application-to-fda-for-allorx-stem-cellr-therapy-of-covid-19/) to assess safety of AlloRx Stem Cells® in the treatment of COVID-19 patients in the US. Recent umbilical cord stem cell therapies in China to fight the Coronavirus has produced encouraging safety and efficacy results. We are establishing strong communication channels with FDA officials to facilitate and expedite review of our application as well as subsequent steps to gain full FDA approval of AlloRx Stem Cells®. The application is presently under review and we are working closely with FDA reviewers to gain authorization to enroll patients. Several clinical centers have expressed interest in our stem cell therapy. We are also pursuing other avenues for Emergency Use Authorization (EUA). The FDA has thus far authorized three separate EUA applications for compassionate use of AlloRx Stem Cells® in COVID-19 patients. Unfortunately, two patients died prior to treatment. A single patient has been treated by three separate dosages of AlloRx Stem Cells® through an authorized EUA by GIOSTAR. There were no adverse events and the patient who has various comorbidities stabilized and exhibited enhanced pulmonary and renal functions during the six weeks following AlloRx Stem Cell® Therapy. While presently intubated and hospitalized in the ICU, this patient is exhibiting gradual improvement. We are presently pursuing additional EUA applications through our collaboration with GIOSTAR https://vitrobiopharma.com/vitro-biopharma-signs-mou-with-GIOSTAR-for-covid-19-ind-using-allorx-stem-cells/. The data obtained from these studies corroborates our studies of safety and efficacy. Mesenchymal Stem Cells ("MSCs") block the cytokine storm that occurs in COVID-19 patients in acute respiratory distress through their powerful anti-inflammatory effects. The cytokine storm leads to the need for assisted breathing by ventilators, transfer to ICU and tremendous burdens on the US health care system. It is important to note that AlloRx Stem Cells® are therapy for other viral attacks including influenza since stem cells block acute respiratory distress and damage to other major organs including cardiovascular, pulmonary and renal systems. AlloRx Stem Cells® are very likely to assist in recovery from failure of various organ systems in COVID-19 survivors, as our case study is demonstrating.

We entered into an exclusive Memorandum of Understanding (MOU) with Global Institute of Stem Cell Therapy and Research, Inc. ("GIOSTAR") a leading stem cell research institute based in San Diego, California to jointly partner together for a separate COVID-19 Investigational New Drug ("IND") application to the FDA using Vitro Biopharma's umbilical cord MSC product AlloRx Stem Cells in a clinical trial to treat Covid-19 patients https://vitrobiopharma.com/vitro-biopharma-signs-mou-with-GIOSTAR-for-covid-19-ind-using-allorx-stem-cells/ GIOSTAR is a worldwide leader in the in the field of stem cell research and has stem cell research and treatment facilities around the world. GIOSTAR is leading the way for filling the joint IND application for a Covid-19 trial with the FDA while Vitro will provide its AlloRx Stem Cells® for use in the study and post-approval stages through a supply agreement with GIOSTAR. GIOSTAR has already obtained EUAs from the FDA for using stem cell treatment for severe Covid-19 hospitalized patients using AlloRx Stem Cells®. https://www.GIOSTAR.com/2020/05/01/GIOSTAR-announces-fda-approval-compassionate-use-treat-covid-19-stem-cells-2/

Vitro will continue to seek FDA authorization of its pending IND. As the approval process proceeds, Vitro will seek AlloRx Stem Cells® FDA approval through Phase 2/3 IND filings for indications other than COVID-19 such as osteoarthritis while at the same time continuing to supply GIOSTAR AlloRx Stem Cells® for treatment of COVID-19 patients in global markets.

GIOSTAR in collaboration with government of Gujarat, India is building one of the world's largest stem cell hospitals. This is a dream project of India's Prime Minister Narendra Modi. The MOU stated the intended discussions regarding the use of AlloRx Stem Cells® at GIOSTAR's various international stem cell facilities that would provide quality and economic advantages.

The company is doubling its laboratory and manufacturing facilities and expanding its clean room by 100% in size and capacity. This new facility is expected to be online during the 1st quarter of next year. This represents approximately $6M of AlloRx Stem Cell Vitro Biopharma revenue capacity per year. Furthermore, the completion of the 2nd clean room processing facility at the beginning of the 2021 year will expand our capacity to approximately 100 Billion AlloRx Stem Cell s a month or approximately $1.7 Million of AlloRx Stem Cell Vitro Biopharma revenue capacity per month. This would give Vitro Biopharma a revenue run rate capacity of $20M a year.

Our increased capacity is rigorously controlled by our Quality Management System, now certified to the ISO9001 Quality and the ISO13485 Medical Device Standards as well. This provides GMP-compliant manufacturing of the highest quality stem cells/medical devices for clinical trial testing to provide further evidence of safety and efficacy for treatment of a wide variety of indications. Highly regulated GMP biologics manufacturing within an FDA-compliant facility provides numerous opportunities to the Company to drive strong revenue growth. We are presently focused on our partnerships in the Caribbean with DVC Stem in Grand Cayman Island, Infinivive MD in the US and emerging opportunities in the Commonwealth of the Bahamas. We are actively pursuing other partnership opportunities as well.

We have reformulated with our Contract Manufacture to produce STEMulize in large quantity manufacturing runs. STEMulize contains natural substances that activate the body's own stem cells to enhance recovery from injury such as TBI, stroke, MS, PD and other autoimmune, inflammatory and neurological diseases. The STEMulize product will be offered as a private label product to Infinivive MD clinics and is being implemented as supplemental support to clinical treatments now ongoing in the Cayman Islands. Patients report positive benefits from STEMulize therapy following stem cell transplants including increased overall energy and enhancement of improved motor function in MS patients. We are currently pursing licensing arrangements with nutraceutical companies that can scale our formulation under their own private label.

The Company's cosmetic stem cell serum private labelled as Infinivive MD Serum is being applied as a topical cosmetic serum in medical spas and plastic surgery offices. Infinivive MD revenue was reduced by the Coronavirus pandemic and as a result, revenues declined by 50% in the quarter to approximately $50,000 vs $100,000 in the prior quarter. This also compares to $50,000 in the current quarter of 2020 vs $130,000 in the prior comparative quarter of 2019.

The Joint Development and Supply Agreement dated May 15th 2018 between Vitro Biopharma and Jack Zamora is being renegotiated due to the Coronavirus pandemic and as such the minimum exclusivity requirements have been delayed by approximately a year.

Infinivive MD Cosmetic Serum is revolutionizing the cosmetic industry. Patients are experiencing unparalleled improvements in the appearance of fine lines and wrinkles. This is one of the fastest growing revenue streams for Vitro Biopharma. We work with a variety of regulatory experts to assist us in the appropriate regulatory pathway. At this point it is regulated as a cosmetic topical product but may be reclassified based on regulatory input.

http://www.jackzamoramd.comwww.infinivivemd.com

Infinivive MD also has an exclusive agreement to distribute AlloRx Stem Cells into the countries of Saudi Arabia, U.A.E., and Colombia. A trial was conducted in Kuwait prior to the pandemic and upon reopening of the country the first commercial orders will be shipped. The agreement calls for minimum commitments to maintain exclusivity and provides for minimum revenue of $250,000 annually in 2020. However due to the worldwide Corona Virus lockdown of business and customers the agreement for performance requirements have been delayed by approximately a year.

Vitro Biopharma's OEM cosmetic topical serum is being distributed exclusively by Infinivive MD into cosmetic clinics that are providing the topical treatment as a beautification product. To date the company's product is being offered in a number of clinics throughout the United States and soon internationally; but with the clinics just opening again for business and with limited occupancy rules we do not expect this revenue to recover back to peak levels with growth until the first half of 2021.

Update on the Clinical Trial of Musculoskeletal Conditions in the Bahamas

This initiative broadens Vitro Biopharma's expansion into highly regulated stem cell trials in collaboration with the Nassau-based Medical Pavilion of the Bahamas (TMPB).

Home

We will now be able to extend stem cell therapy based on our novel, patent-pending AlloRx Stem Cell product to a variety of musculoskeletal conditions. These include OA of any joint, ACL/MCL tear, Achilles tendon rupture, rotator cuff injury, tennis elbow and herniated disc that are highly prevalent and have few disease-modifying options. It is important to note that many stem cell treatments now performed are problematic due to limited potency and failure to meet basic qualification criteria of MSC stem cells.. Also, contamination due to poor production methods that are not in compliance with FDA regulations has caused serious complications, resulting in FDA warning letters due to manufacturing infractions. Vitro Biopharma operates a highly regulated, FDA-compliant commercial biologics manufacturing operation for several years and is cGMP compliant, ISO 9001 Certified, ISO 13485 Certified, CLIA Certified and FDA registered. All manufacturing occurs in a certified sterile clean room with extensive and advanced testing to assure the absence of contamination. Furthermore, in numerous patients treated to date by IV infusion of AlloRx Stem Cells there have been no significant adverse events.''

The company is partnered with Dr. Conville Brown, MD, MBBS, FACC, FESC, PhD, the founder and CEO of the Medical Pavilion of the Bahamas who is the Principal Investigator of this trial and director of its clinical administration. Dr Brown was instrumental in the establishment of the National Stem Cell Ethics Committee in the Bahamas.

About the Medical Pavilion of the Bahamas: TMPB operates within a 40,000 square foot building as a partnered care specialty medical facility with 10 different centers in various areas including cardiology, cancer, clinical research and kidney disease. One of the centers is the Partners Stem Cell Centre, where the present trial will be conducted. The Partners Stem Cell Centre provides an environment to conduct stem cell research and clinical trials under the model of ''FDA rigor in a Non-FDA Jurisdiction'' TMPB employs 20 medical specialists in various fields. See http://www.tmp-bahamas.com for additional information.

The company expects to begin patient enrollment for the clinical trial in late QIV but does not expect to realize revenue until QI/QII of 2021.

Due to the Corona virus pandemic the Cayman Islands closed itself and its businesses down for the majority of the quarter and next quarter, the current status is listed as locked down until Sept. 1st 2020. However, our partner reports that customers are staying on the waiting list and will return for their treatments as soon as the island opens back up. There currently is a backlog of patients of over 40 treatments pending which exceeds all of the treatments performed in 2019. We expect to see a surge in revenues from this backlog to bring back our revenue stream in the fourth quarter of 2020 and into the first half of 2021.

The Company has several patent applications (11) pending in the US and foreign jurisdictions. These patents cover our AlloRx Stem Cell line and various aspects of our STEMulize stem cell activation products & processes as well as specific diagnostic tests of stem cell activity and therapeutic effectiveness. During the quarter, the Company has responded to office actions and continues to vigorously prosecute & expand its patent filings.

Dr. Jim Musick, CEO of Vitro Biopharma, said, "We are pleased to report our activities in fighting the Covid-19 with filings of our eIND and INDs and partnership with GIOSTAR. While we are disappointed in the extraordinary impact of the Corona Virus pandemic and its results on our operations, we have taken the time to advance our clinical applications and partnerships in further preparation for realized growth in 2021 as a result of these activities.

Our stem cell products are distinctly superior to stem cell transplants in the USA. The latter usually involve use of impure products lacking validation as stem cells and containing insufficient numbers of stem cells to achieve therapeutic benefits. These are produced without regulatory oversight and have been known to cause serious adverse effects. Hence the use of highly purified and well characterized stem cells (AlloRx Stem Cells) is needed to provide safety and efficacy in regenerative medicine therapies.

In summary, Vitro Biopharma is advancing as a key player in regenerative medicine with 10+ years' experience in the development and commercialization of stem cell products for research, recognized by a Best in Practice Technology Innovation Leadership award for Stem Cell Tools and Technology and a growing track record of successful translation to therapy. We plan to leverage our proprietary technology platform to the establishment of international Stem Cell Centers of Excellence and regulatory approvals in the US and worldwide.

Vitro Biopharma has supplied major biopharmaceutical firms, elite university laboratories and clinical trials worldwide with its Umbilical Cord Mesenchymal Stem Cells (AlloRx Stem Cells), and it's MSC-Grow Brand of cell culture media along with advanced stem cell diagnostic services. http://www.vitrobiopharma.com

Sincerely yours,

James R. Musick, PhD. President, CEO & Chairman of the Board http://www.vitrobiopharma.com

Forward-Looking Statements

Statements herein regarding financial performance have not yet been reported to the SEC nor reviewed by the Company's auditors. Certain statements contained herein and subsequent statements made by and on behalf of the Company, whether oral or written may contain "forward-looking statements". Such forward looking statements are identified by words such as "intends," "anticipates," "believes," "expects" and "hopes" and include, without limitation, statements regarding the Company's plan of business operations, product research and development activities, potential contractual arrangements, receipt of working capital, anticipated revenues and related expenditures. Factors that could cause actual results to differ materially include, among others, acceptability of the Company's products in the market place, general economic conditions, receipt of additional working capital, the overall state of the biotechnology industry and other factors set forth in the Company's filings with the Securities and Exchange Commission. Most of these factors are outside the control of the Company. Investors are cautioned not to put undue reliance on forward-looking statements. Except as otherwise required by applicable securities statutes or regulations, the Company disclaims any intent or obligation to update publicly these forward- looking statements, whether as a result of new information, future events or otherwise.

CONTACT:

Dr. James Musick Chief Executive Officer Vitro BioPharma (303) 999-2130 Ext. 3 E-mail: jim@vitrobiopharma.com http://www.vitrobiopharma.com

Vitro Diagnostics, Inc.

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Quarter Ended April 30th;

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Excerpt from:
Vitro Bio-Pharma 2nd Quarter Ended April 30th 2020 Financial Results of Operations and Shareholder Letter - Stockhouse

KENILWORTH, N.J.--(BUSINESS WIRE)--Merck (NYSE: MRK), known as MSD outside the United States and Canada, announced today that the U.S. Food and Drug Administration (FDA) has approved KEYTRUDA, Mercks anti-PD-1 therapy, as monotherapy for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) that is not curable by surgery or radiation. This approval is based on data from the Phase 2 KEYNOTE-629 trial, in which KEYTRUDA demonstrated meaningful efficacy and durability of response, with an objective response rate (ORR) of 34% (95% CI, 25-44), including a complete response rate of 4% and a partial response rate of 31%. Among responding patients, 69% had ongoing responses of six months or longer. After a median follow-up time of 9.5 months, the median duration of response (DOR) had not been reached (range, 2.7 to 13.1+ months).

Cutaneous squamous cell carcinoma is the second most common form of skin cancer, said Dr. Jonathan Cheng, vice president, clinical research, Merck Research Laboratories. In KEYNOTE-629, treatment with KEYTRUDA resulted in clinically meaningful and durable responses. Todays approval is great news for patients with cSCC and further demonstrates our commitment to bringing new treatment options to patients with advanced, difficult-to-treat cancers.

Immune-mediated adverse reactions, which may be severe or fatal, can occur with KEYTRUDA, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and renal dysfunction, severe skin reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation (HSCT). Based on the severity of the adverse reaction, KEYTRUDA should be withheld or discontinued and corticosteroids administered if appropriate. KEYTRUDA can also cause severe or life-threatening infusion-related reactions. Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. For more information, see Selected Important Safety Information below.

Data Supporting Approval

The efficacy of KEYTRUDA was investigated in patients with recurrent or metastatic cSCC enrolled in KEYNOTE-629 (NCT03284424), a multi-center, multi-cohort, non-randomized, open-label trial. The trial excluded patients with autoimmune disease or a medical condition that required immunosuppression. The major efficacy outcome measures were ORR and DOR as assessed by blinded independent central review (BICR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, modified to follow a maximum of 10 target lesions and a maximum of five target lesions per organ.

Among the 105 patients treated, 87% received one or more prior lines of therapy and 74% received prior radiation therapy. Forty-five percent of patients had locally recurrent only cSCC, 24% had metastatic only cSCC and 31% had both locally recurrent and metastatic cSCC. The study population characteristics were: median age of 72 years (range, 29 to 95); 71% age 65 or older; 76% male; 71% White; 25% race unknown; 34% Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 and 66% ECOG PS of 1.

KEYTRUDA demonstrated an ORR of 34% (95% CI, 25-44) with a complete response rate of 4% and a partial response rate of 31%. Among the 36 responding patients, 69% had ongoing responses of six months or longer. After a median follow-up time of 9.5 months, the median DOR had not been reached (range, 2.7 to 13.1+ months).

Patients received KEYTRUDA 200 mg intravenously every three weeks until documented disease progression, unacceptable toxicity or a maximum of 24 months. Patients with initial radiographic disease progression could receive additional doses of KEYTRUDA during confirmation of progression unless disease progression was symptomatic, rapidly progressive, required urgent intervention, or occurred with a decline in performance status. Assessment of tumor status was performed every six weeks during the first year and every nine weeks during the second year.

Among the 105 patients with cSCC enrolled in KEYNOTE-629, the median duration of exposure to KEYTRUDA was 5.8 months (range, 1 day to 16.1 months). Patients with autoimmune disease or a medical condition that required systemic corticosteroids or other immunosuppressive medications were ineligible. Adverse reactions occurring in patients with cSCC were similar to those occurring in 2,799 patients with melanoma or non-small cell lung cancer (NSCLC) treated with KEYTRUDA as a single agent. Laboratory abnormalities (Grades 3-4) that occurred at a higher incidence included lymphopenia (11%).

About KEYTRUDA (pembrolizumab) Injection, 100 mg

KEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of the bodys immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industrys largest immuno-oncology clinical research program. There are currently more than 1,200 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

Selected KEYTRUDA (pembrolizumab) Indications

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.

KEYTRUDA is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection.

Non-Small Cell Lung Cancer

KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) 1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is stage III where patients are not candidates for surgical resection or definitive chemoradiation, or metastatic.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS 1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

Small Cell Lung Cancer

KEYTRUDA is indicated for the treatment of patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy and at least 1 other prior line of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Head and Neck Squamous Cell Cancer

KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [combined positive score (CPS) 1] as determined by an FDA-approved test.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy.

Classical Hodgkin Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory classical Hodgkin lymphoma (cHL), or who have relapsed after 3 or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Primary Mediastinal Large B-Cell Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.

Urothelial Carcinoma

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 [combined positive score (CPS) 10], as determined by an FDA-approved test, or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

KEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.

Microsatellite Instability-High (MSI-H) Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR)

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.

Gastric Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Esophageal Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1 (CPS 10) as determined by an FDA-approved test, with disease progression after one or more prior lines of systemic therapy.

Cervical Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Hepatocellular Carcinoma

KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Merkel Cell Carcinoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Renal Cell Carcinoma

KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

Tumor Mutational Burden-High Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options.

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.

Cutaneous Squamous Cell Carcinoma

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) that is not curable by surgery or radiation.

Selected Important Safety Information for KEYTRUDA

Immune-Mediated Pneumonitis

KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases. Pneumonitis occurred in 3.4% (94/2799) of patients with various cancers receiving KEYTRUDA, including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%). Pneumonitis occurred in 8.2% (65/790) of NSCLC patients receiving KEYTRUDA as a single agent, including Grades 3-4 in 3.2% of patients, and occurred more frequently in patients with a history of prior thoracic radiation (17%) compared to those without (7.7%). Pneumonitis occurred in 6% (18/300) of HNSCC patients receiving KEYTRUDA as a single agent, including Grades 3-5 in 1.6% of patients, and occurred in 5.4% (15/276) of patients receiving KEYTRUDA in combination with platinum and FU as first-line therapy for advanced disease, including Grades 3-5 in 1.5% of patients.

Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.

Immune-Mediated Colitis

KEYTRUDA can cause immune-mediated colitis. Colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 2 (0.4%), 3 (1.1%), and 4 (<0.1%). Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.

Immune-Mediated Hepatitis (KEYTRUDA) and Hepatotoxicity (KEYTRUDA in Combination With Axitinib)

Immune-Mediated Hepatitis

KEYTRUDA can cause immune-mediated hepatitis. Hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.4%), and 4 (<0.1%). Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.

Hepatotoxicity in Combination With Axitinib

KEYTRUDA in combination with axitinib can cause hepatic toxicity with higher than expected frequencies of Grades 3 and 4 ALT and AST elevations compared to KEYTRUDA alone. With the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased ALT (20%) and increased AST (13%) were seen. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider more frequent monitoring of liver enzymes as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt KEYTRUDA and axitinib, and consider administering corticosteroids as needed.

Immune-Mediated Endocrinopathies

KEYTRUDA can cause adrenal insufficiency (primary and secondary), hypophysitis, thyroid disorders, and type 1 diabetes mellitus. Adrenal insufficiency occurred in 0.8% (22/2799) of patients, including Grade 2 (0.3%), 3 (0.3%), and 4 (<0.1%). Hypophysitis occurred in 0.6% (17/2799) of patients, including Grade 2 (0.2%), 3 (0.3%), and 4 (<0.1%). Hypothyroidism occurred in 8.5% (237/2799) of patients, including Grade 2 (6.2%) and 3 (0.1%). The incidence of new or worsening hypothyroidism was higher in 1185 patients with HNSCC (16%) receiving KEYTRUDA, as a single agent or in combination with platinum and FU, including Grade 3 (0.3%) hypothyroidism. Hyperthyroidism occurred in 3.4% (96/2799) of patients, including Grade 2 (0.8%) and 3 (0.1%), and thyroiditis occurred in 0.6% (16/2799) of patients, including Grade 2 (0.3%). Type 1 diabetes mellitus, including diabetic ketoacidosis, occurred in 0.2% (6/2799) of patients.

Monitor patients for signs and symptoms of adrenal insufficiency, hypophysitis (including hypopituitarism), thyroid function (prior to and periodically during treatment), and hyperglycemia. For adrenal insufficiency or hypophysitis, administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA for Grade 2 adrenal insufficiency or hypophysitis and withhold or discontinue KEYTRUDA for Grade 3 or Grade 4 adrenal insufficiency or hypophysitis. Administer hormone replacement for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and administer antihyperglycemics in patients with severe hyperglycemia.

Immune-Mediated Nephritis and Renal Dysfunction

KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.1%), and 4 (<0.1%) nephritis. Nephritis occurred in 1.7% (7/405) of patients receiving KEYTRUDA in combination with pemetrexed and platinum chemotherapy. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue for Grade 3 or 4 nephritis.

Immune-Mediated Skin Reactions

Immune-mediated rashes, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) (some cases with fatal outcome), exfoliative dermatitis, and bullous pemphigoid, can occur. Monitor patients for suspected severe skin reactions and based on the severity of the adverse reaction, withhold or permanently discontinue KEYTRUDA and administer corticosteroids. For signs or symptoms of SJS or TEN, withhold KEYTRUDA and refer the patient for specialized care for assessment and treatment. If SJS or TEN is confirmed, permanently discontinue KEYTRUDA.

Other Immune-Mediated Adverse Reactions

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue in patients receiving KEYTRUDA and may also occur after discontinuation of treatment. For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA and administer corticosteroids. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. Resume KEYTRUDA when the adverse reaction remains at Grade 1 or less following corticosteroid taper. Permanently discontinue KEYTRUDA for any Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.

The following clinically significant immune-mediated adverse reactions occurred in less than 1% (unless otherwise indicated) of 2799 patients: arthritis (1.5%), uveitis, myositis, Guillain-Barr syndrome, myasthenia gravis, vasculitis, pancreatitis, hemolytic anemia, sarcoidosis, and encephalitis. In addition, myelitis and myocarditis were reported in other clinical trials, including classical Hodgkin lymphoma, and postmarketing use.

Treatment with KEYTRUDA may increase the risk of rejection in solid organ transplant recipients. Consider the benefit of treatment vs the risk of possible organ rejection in these patients.

Infusion-Related Reactions

KEYTRUDA can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, which have been reported in 0.2% (6/2799) of patients. Monitor patients for signs and symptoms of infusion-related reactions. For Grade 3 or 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Immune-mediated complications, including fatal events, occurred in patients who underwent allogeneic HSCT after treatment with KEYTRUDA. Of 23 patients with cHL who proceeded to allogeneic HSCT after KEYTRUDA, 6 (26%) developed graft-versus-host disease (GVHD) (1 fatal case) and 2 (9%) developed severe hepatic veno-occlusive disease (VOD) after reduced-intensity conditioning (1 fatal case). Cases of fatal hyperacute GVHD after allogeneic HSCT have also been reported in patients with lymphoma who received a PD-1 receptorblocking antibody before transplantation. Follow patients closely for early evidence of transplant-related complications such as hyperacute graft-versus-host disease (GVHD), Grade 3 to 4 acute GVHD, steroid-requiring febrile syndrome, hepatic veno-occlusive disease (VOD), and other immune-mediated adverse reactions.

In patients with a history of allogeneic HSCT, acute GVHD (including fatal GVHD) has been reported after treatment with KEYTRUDA. Patients who experienced GVHD after their transplant procedure may be at increased risk for GVHD after KEYTRUDA. Consider the benefit of KEYTRUDA vs the risk of GVHD in these patients.

Increased Mortality in Patients With Multiple Myeloma

In trials in patients with multiple myeloma, the addition of KEYTRUDA to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of these patients with a PD-1 or PD-L1 blocking antibody in this combination is not recommended outside of controlled trials.

Embryofetal Toxicity

Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. Advise women of this potential risk. In females of reproductive potential, verify pregnancy status prior to initiating KEYTRUDA and advise them to use effective contraception during treatment and for 4 months after the last dose.

Adverse Reactions

In KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9% of 555 patients with advanced melanoma; adverse reactions leading to permanent discontinuation in more than one patient were colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). The most common adverse reactions (20%) with KEYTRUDA were fatigue (28%), diarrhea (26%), rash (24%), and nausea (21%).

In KEYNOTE-002, KEYTRUDA was permanently discontinued due to adverse reactions in 12% of 357 patients with advanced melanoma; the most common (1%) were general physical health deterioration (1%), asthenia (1%), dyspnea (1%), pneumonitis (1%), and generalized edema (1%). The most common adverse reactions were fatigue (43%), pruritus (28%), rash (24%), constipation (22%), nausea (22%), diarrhea (20%), and decreased appetite (20%).

In KEYNOTE-054, KEYTRUDA was permanently discontinued due to adverse reactions in 14% of 509 patients; the most common (1%) were pneumonitis (1.4%), colitis (1.2%), and diarrhea (1%). Serious adverse reactions occurred in 25% of patients receiving KEYTRUDA. The most common adverse reaction (20%) with KEYTRUDA was diarrhea (28%).

In KEYNOTE-189, when KEYTRUDA was administered with pemetrexed and platinum chemotherapy in metastatic nonsquamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 20% of 405 patients. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonitis (3%) and acute kidney injury (2%). The most common adverse reactions (20%) with KEYTRUDA were nausea (56%), fatigue (56%), constipation (35%), diarrhea (31%), decreased appetite (28%), rash (25%), vomiting (24%), cough (21%), dyspnea (21%), and pyrexia (20%).

In KEYNOTE-407, when KEYTRUDA was administered with carboplatin and either paclitaxel or paclitaxel protein-bound in metastatic squamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 15% of 101 patients. The most frequent serious adverse reactions reported in at least 2% of patients were febrile neutropenia, pneumonia, and urinary tract infection. Adverse reactions observed in KEYNOTE-407 were similar to those observed in KEYNOTE-189 with the exception that increased incidences of alopecia (47% vs 36%) and peripheral neuropathy (31% vs 25%) were observed in the KEYTRUDA and chemotherapy arm compared to the placebo and chemotherapy arm in KEYNOTE-407.

In KEYNOTE-042, KEYTRUDA was discontinued due to adverse reactions in 19% of 636 patients with advanced NSCLC; the most common were pneumonitis (3%), death due to unknown cause (1.6%), and pneumonia (1.4%). The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia (7%), pneumonitis (3.9%), pulmonary embolism (2.4%), and pleural effusion (2.2%). The most common adverse reaction (20%) was fatigue (25%).

In KEYNOTE-010, KEYTRUDA monotherapy was discontinued due to adverse reactions in 8% of 682 patients with metastatic NSCLC; the most common was pneumonitis (1.8%). The most common adverse reactions (20%) were decreased appetite (25%), fatigue (25%), dyspnea (23%), and nausea (20%).

Adverse reactions occurring in patients with SCLC were similar to those occurring in patients with other solid tumors who received KEYTRUDA as a single agent.

In KEYNOTE-048, KEYTRUDA monotherapy was discontinued due to adverse events in 12% of 300 patients with HNSCC; the most common adverse reactions leading to permanent discontinuation were sepsis (1.7%) and pneumonia (1.3%). The most common adverse reactions (20%) were fatigue (33%), constipation (20%), and rash (20%).

In KEYNOTE-048, when KEYTRUDA was administered in combination with platinum (cisplatin or carboplatin) and FU chemotherapy, KEYTRUDA was discontinued due to adverse reactions in 16% of 276 patients with HNSCC. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonia (2.5%), pneumonitis (1.8%), and septic shock (1.4%). The most common adverse reactions (20%) were nausea (51%), fatigue (49%), constipation (37%), vomiting (32%), mucosal inflammation (31%), diarrhea (29%), decreased appetite (29%), stomatitis (26%), and cough (22%).

In KEYNOTE-012, KEYTRUDA was discontinued due to adverse reactions in 17% of 192 patients with HNSCC. Serious adverse reactions occurred in 45% of patients. The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. The most common adverse reactions (20%) were fatigue, decreased appetite, and dyspnea. Adverse reactions occurring in patients with HNSCC were generally similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy, with the exception of increased incidences of facial edema and new or worsening hypothyroidism.

In KEYNOTE-087, KEYTRUDA was discontinued due to adverse reactions in 5% of 210 patients with cHL. Serious adverse reactions occurred in 16% of patients; those 1% included pneumonia, pneumonitis, pyrexia, dyspnea, GVHD, and herpes zoster. Two patients died from causes other than disease progression; 1 from GVHD after subsequent allogeneic HSCT and 1 from septic shock. The most common adverse reactions (20%) were fatigue (26%), pyrexia (24%), cough (24%), musculoskeletal pain (21%), diarrhea (20%), and rash (20%).

In KEYNOTE-170, KEYTRUDA was discontinued due to adverse reactions in 8% of 53 patients with PMBCL. Serious adverse reactions occurred in 26% of patients and included arrhythmia (4%), cardiac tamponade (2%), myocardial infarction (2%), pericardial effusion (2%), and pericarditis (2%). Six (11%) patients died within 30 days of start of treatment. The most common adverse reactions (20%) were musculoskeletal pain (30%), upper respiratory tract infection and pyrexia (28% each), cough (26%), fatigue (23%), and dyspnea (21%).

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FDA Approves Merck's KEYTRUDA (pembrolizumab) for the Treatment of Patients with Recurrent or Metastatic Cutaneous Squamous Cell Carcinoma (cSCC) that...

NEW HAVEN, Conn.--(BUSINESS WIRE)--Simcha Therapeutics, a biotechnology company developing first-in-class biologic drugs that modulate powerful cytokine pathways, launched today with $25 million in Series A financing and a mission to harness the precision and power of the immune system through the use of directed evolution.

Simchas lead program involves a customized variant of interleukin-18 (IL-18), a cytokine with potent antitumor effects, developed in the lab of Scientific Founder Aaron Ring, M.D., Ph.D., Assistant Professor of Immunobiology at the Yale School of Medicine. The biology and preclinical profile of this molecule, which Simcha expects to advance to the clinic in the first half of 2021, is described in detail in a scientific paper published today in the journal Nature.

Cytokine therapies heralded the immuno-oncology revolution more than 30 years ago with the discovery that interleukin-2 (IL-2) could promote rare, but dramatic, responses in melanoma and kidney cancer patients. However, they have not lived up to their promise as a class due to substantial toxicities and limited efficacy. Simcha was founded to overcome those obstacles by using directed evolution to engineer a new generation of cytokines with improved properties relative to those of their native variants. Simchas molecules are purpose-built to control immune cell activation, differentiation and proliferation and to reverse the immunosuppressive tumor microenvironment that is a barrier to effective eradication of the cancer.

Cytokines represent a compelling therapeutic class because they tap into pathways that are hard-wired into immune cells. The challenge is that nature didnt design them to be anti-cancer therapies; theyre signaling molecules, so their activity can be hard to specifically direct, Dr. Ring said. At Simcha, we set out to improve on natures design by engineering custom-built proteins that can precisely activate and expand populations of crucial immune responders, such as natural killer (NK) cells and T cells. Too many cancer patients do not respond to the immunotherapies available today. Were hopeful that our approach will provide new options and potential benefits to these patients.

Evading a Decoy Receptor

Simchas lead asset, ST-067, activates the IL-18 receptor, triggering potent inflammatory signaling in antitumor immune cells of both the adaptive and innate branches of the immune system.

Early efforts by leading pharmaceutical companies to develop IL-18 into a drug failed. Dr. Rings lab broke new ground by identifying the reason for that failure: The tumor microenvironment is teeming with a decoy called IL-18BP, which binds IL-18 and blocks it from activating its receptor. When infused as a drug, IL-18 is drawn to the decoy and fails to reach its true target. As described in the Nature paper, the decoy receptor is a major barrier to IL-18 immunotherapy.

To overcome that barrier, Dr. Rings lab used directed evolution to create a version of the cytokine that would evade the decoy and bind only to the true IL-18 receptor. This was a difficult task, since IL-18 normally binds its decoy 10,000 times tighter than it does to the IL-18 receptor. The designer version of IL-18 made in Rings lab has dramatic alterations in its receptor binding properties, biasing binding towards the IL-18 receptor and away from the decoy by more than one million-fold. This decoy-resistant property enables the custom-built cytokine to work effectively in the immunosuppressive tumor microenvironment.

Potent Single-agent Antitumor Effects

When Rings lab tested the decoy-resistant IL-18 and compared it to natural IL-18 in mice, they found that just as in human patients natural IL-18 had little to no antitumor activity. By contrast, the decoy-resistant IL-18 had potent single-agent activity that inhibited tumor growth and even produced complete tumor regression in many animals, including in tumor types that are refractory to checkpoint inhibitors.

Rings lab also examined the effect of decoy-resistant IL-18 on the tumor microenvironment. A key finding: The engineered IL-18 acted on a crucial population of stem-like T cells within tumors, increasing their numbers over tenfold and skewing their development toward a highly active effector phenotype, as opposed to an exhausted or dysfunctional state. In checkpoint-resistant tumors, the engineered IL-18 also acted on innate NK cells, increasing their numbers and maturation to promote antitumor activity.

The mechanism of action of decoy-resistant IL-18 is unique and distinct from immunotherapeutic agents that are being developed for other pathways. For this reason, we are hopeful it could be effective in tumors that have not otherwise responded to immune-based treatments, as well as enhance the activity of standard cancer immunotherapies, said Dr. Ring.

Founders Strong Record in IO Drug Discovery

Dr. Ring has a strong track record in immuno-oncology drug discovery. He co-invented the first described CD122-biased IL-2 variant, originally detailed in Nature in 2012, which is now advancing through preclinical studies at Medicenna Therapeutics. He also developed a high-affinity SIRP antagonist, featured in Science in 2013, that is now in clinical development at ALX Oncology as ALX-148. For these and other discoveries, Ring was named to Forbes 30 under 30 list of rising stars in health care in 2016 and has been honored with an NIH Directors Early Independence Award and recognition as a Pew-Stewart Scholar in Cancer Research.

Simcha plans to build out a full executive team as the company prepares to move ST-067 into the clinic next year.

The companys investors include WuXi AppTecs Corporate Venture Fund, Sequoia Capital China and Connecticut Innovations.

About Simcha Therapeutics

Simcha Therapeutics uses directed evolution to engineer novel cytokines designed to unlock the precision and power of the immune system. Simchas lead program, ST-067, is a designer IL-18 cytokine that has shown potent antitumor effects in animal models, both as a monotherapy and when combined with anti-PD-1 checkpoint inhibitors, as described in Nature in June 2020. A Phase 1 trial is expected to be launched in the first half of 2021. Simcha was founded by Aaron Ring, M.D., Ph.D., Assistant Professor of Immunobiology at the Yale School of Medicine. The company has received $25 million in funding to date and is based in New Haven, Conn.

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Simcha Therapeutics Launches to Engineer Therapeutic Cytokines to Unlock the Full Potential of the Immune System - Business Wire

Edward Pierce, 49, an acclaimed Broadway set designer for plays like Wicked spent five weeks in a medically induced coma after contracting COVID-19 and was treated at a hospital in Teaneck, New Jersey.

His condition slowly deteriorated due to organ failure, and there seemed to be little hope, so his wife agreed to use an untested method developed by an Israeli biotechnology firm. He made history as the first American to receive placental cells in around 15 parts of his body.

According to the Daily Mail, Pierce was off a ventilator and breathing on his own just within ten days of treatment. The treatment is said to be part of the Food and Drugs Administrations' 'compassionate use.'

Pierce first thought that he had the flu, so doctors only prescribed him medicines and told him to stay home. However, his condition continued to worsen, and then he was admitted to the hospital. Four days later, he was put on a ventilator.

At one point in his stay, doctors had to restart his heart after it stopped when he pulled out his breathing tube. Pierce told The Daily Beast that he felt scared at the time because he does not want to be not in control.

He remembered that doctors asked him to count backwards from 10 and her wife told him that she loves him, and he said it back to her. That was the last thing he remembered before waking up five weeks later.

A lot has happened in those times, including him having kidney failure and needing dialysis. Luckily, he did not have to have that. His wife began thinking of what life would be like if Pierce did not make it. She would receive updates from the hospital, sometimes the news was good, sometimes it was not so good.

According to Pixie, the doctors are running out of options to save her husband. So they ask her to authorize an as-yet-untested treatment that extracts stem cells from human placenta.

Read Also: 115 Healthy Babies have Been Born from Mothers Infected with COVID-19 In India

Pluristem Therapeutics, an Israeli company who pioneered the treatment said that 75% of COVID-19 patients had been taken off the ventilator, according to The Jerusalem Post. The FDA permitted the company to offer the treatment on a case-by-case basis to patients under 'compassionate use.'

Compassionate use is the use of a new unapproved treatment for patients who are seriously ill and has not shown any improvements after every other option has been exhausted.

The proposed treatment includes using cells from the placenta or the intramuscular administration of the company's PLX-PAD, which is used for severe pneumonia caused by COVID-19 and preventing the deterioration of patients towards ARDS and sepsis.

Within ten days, Pierce was taken off a ventilator and started to breathe on his own. Gradually, doctors weaned him off of sedatives, and three days after he woke up, his breathing tubes, feeding tubes, and catheters were all removed.

Finally, on May 1, he was discharged from the hospital after nearly seven weeks of treatment. He was then sent to rehabilitation to rebuild his muscles and regain strength.

Read More: CDC Emphasized COVID-19 Not Easily Spread By Touching Surfaces or Objects

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First American to Receive Placental Cell Treatment For COVID-19 is an Acclaimed Broadway Scenic Designer - Science Times

BUFFALO, N.Y. For decades, the enormous disease-curing potential of human stem cells has been thwarted by the inability to produce sufficient quantities of mature human cells in vivo in a living organism.

Now, a team led by University at Buffalo scientists has developed a method that dramatically ramps up production of mature human cells in mouse embryos. Producing human cells in vivo is critical because cells made in a petri dish often do not behave the same way that cells do in the body.

The research was published on May 13 in Science Advances.

This is fundamental research that allows us to use the mouse embryo to help us better understand human development, said Jian Feng, PhD, corresponding author and professor of physiology and biophysics in the Jacobs School of Medicine and Biomedical Sciences at UB.

Further development of our technology could enable the generation of even larger quantities of specific types of mature human cells to allow us to create more effective mouse models to study diseases that gravely affect humans, such as malaria or COVID-19, said Feng.

And because this method produces so many mature human cells, it could potentially generate materials to treat chronic diseases, such as diabetes or kidney failure, by replacing a patients damaged cells with healthy human cells or tissues.

Infectious disease applications

Feng explained that it might be possible to create a much better mouse model of the human immune system or components of the human respiratory system in order to study COVID-19, a disease that wreaks havoc in humans, but barely affects mice.

It could also be possible to use the new method to produce mice with even more mature human red blood cells. Such mice would be very effective in the study of malaria, a disease which affects only humans by destroying our red blood cells.

We have a lot of questions to answer before the technology can be useful, but this is the first time that anyone has generated so many mature human cells in a mouse embryo, said Feng.

Millions of mature human cells in 17 days

Previous efforts to produce human cells in mouse embryos have generated small amounts of immature cells that are hard to quantify. In contrast, the UB method resulted in millions of mature human cells in a mouse embryo in 17 days.

In this study, the researchers injected 10-12 nave human stem cells into a mouse blastocyst when it was 3.5 days old. The mouse embryo then generated millions of mature human cells, including red blood cells, eye cells and liver cells, as it developed.

We know that up to four percent of the total number of cells in the mouse embryo were human cells, Feng. This is a low estimate because we cannot quantify the large amount of human red blood cells generated in the mouse embryo.

He said that because these mature human red blood cells do not have a nucleus, they are not counted by the method that the scientists use to quantify the total number of cells.

The teams technique involved overcoming an important challenge: Converting human pluripotent stem cells, which can differentiate into all types of cells in the body, into a form that is compatible with the inner cell mass inside a mouse blastocyst a three-day old mouse embryo. The human stem cells are in a primed state, whereas the inner cell mass inside the mouse blastocyst is in a nave state.

When the primed human cells are put into the mouse blastocyst, they fail to develop, said Feng, noting that the mismatch between the cells different developmental stages seems to be responsible.

We wanted to see if it was possible for the human primed cells to go back to the nave state, just like the pluripotent stem cells inside a mouse blastocyst, said Feng. This is what we have done.

Our method is to transiently inhibit the mTOR kinase for three hours to shock the human primed cells to the nave state, said Feng. Blocking the mTOR kinase triggers a series of events that rewire gene expression and cellular metabolism so that the primed cells become nave.

Converting the later stage human primed stem cells back to an earlier, less developed nave state allowed the human stem cells to co-develop with the inner cell mass in a mouse blastocyst.

The injected human stem cells now develop at the much more rapid pace of the mouse embryo, supporting the generation of millions of mature human cells in 17 days, said Feng.

In addition to Feng, UB co-authors are Zhixing Hu, Hanqin Li, Houbo Jiang, Yong Ren, and Boyang Zhang of the Department of Physiology and Biophysics, and Xinyang Yu and Michael J. Buck of the Department of Biochemistry, all of the Jacobs School. Other co-authors are Jingxin Qiu and Aimee B. Stablewski of the Roswell Park Comprehensive Cancer Center.

Funding for this research was provided by NYSTEM and the Buffalo Blue Sky Initiative.

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Scientists generate millions of mature human cells, far more than have ever been produced - UB News Center

Scientists have placed more mature human cells in mouse embryos. The progress is expected to help the medical community improve the development of treatments, including those for COVID-19.

Over the past decades, scientists faced challenges in producing enough amounts of human cells in animals. It is important to grow human cells in other living organisms in the lab since cells made in a petri dish commonly do not behave like those in the body, Futurity reported.

This is fundamental research that allows us to use the mouse embryo to help us better understand human development, Jian Feng, corresponding study author and a professor in the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo, said in a statement.

He added that the study, described in the journal Science Advances, marks the first time that so many mature human cells were generated in a mouse embryo. The new approach provided millions of mature human cells and took only 17 days to produce such amounts in the lab.

Researchers tested the approach with a mouse blastocyst, a three-day-old embryo. It involved injecting human stem cells into the animal and converting the cells to become compatible with the inner cell mass inside a mouse embryo.

Putting the human stem cells into the naive state allowed them to co-develop with the cells in the mouse. The process then helped the embryo produce millions of mature human cells, including red blood cells, eye cells and liver cells.

Feng said having higher amounts of human cells may help improve how scientists understand human development and disease. It provides a better mouse model to study health conditions, such as diabetes, kidney failure and even COVID-19.

Further development of our technology could enable the generation of even larger quantities of specific types of mature human cells to allow us to create more effective mouse models to study diseases that gravely affect humans, the researcher said.

Improving the approach may also eventually allow scientists to produce more mature human red blood cells in mice. That would help explore health problems and disease that mainly affect red blood cells.

Scientists at the University at Buffalo used a new method that helped them produce millions of mature human cells in a mouse embryo, a progress that may help improve study of common diseases, like diabetes, malaria and COVID-19. Pixabay

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Heres The Reason Why Scientists Are Growing Human Cells In Mouse Embryo - Medical Daily

More than 200,000 people have died from COVID-19 since January 2020. While Australia has been relatively spared from the onslaught of infections and deaths, our nations scientists need to be part of the global effort to address this pandemic.

Research Group Head, Amnion Cell Biology

There is no effective treatment to address the ongoing damage caused by for severe COVID-19 infections, said Associate Professor Rebecca Lim, Research Group Head of Amnion Cell Biology at Hudson Institute. Our team is investigating whether a cell therapy can be effective.

Amniotic epithelial cells (amnion cells) are from the amniotic sac which surrounds a baby during pregnancy. They have stem cell-like properties and can grow into many cell types. Most importantly, they have potent effects on inflammation and tissue damage.

A/Prof Lim and Professor Euan Wallace (Clinical Director, The Ritchie Centre) are developing a clinical trial to investigate whether these cells can help treat patients with COVID-19.

The team is working closely with intensivists at Monash Healths Intensive Care Unit to deliver a Phase 1b/2a clinical trial for COVID-19 positive patients requiring hospitalisation.

The goal of the trial is to determine if allogeneic amniotic epithelial cells are an effective therapy for severe COVID-19 complications. Specifically, the trial will test whether the cells can significantly reduce the cytokine storm associated with COVID-19 infection, encourage lung tissue to repair, and reduce the incidence of blood clotting and subsequent multi-organ complications including strokes, liver and kidney failure.

We have already shown that the allogeneic amniotic epithelial cells are safe and well-tolerated in extremely premature neonates and acutely unwell adults. So far, we have observed improvements in adult patients with liver disease and severe stroke. This points to the likely benefits for patients with COVID-19. These cells may also reduce the incidence and severity of the disease damage caused by blood clotting in tissues, A/Prof Lim said.

This project involves a partnership between Hudson Institute, Monash Health and Monash University-a team that leads the way in Victoria in cell therapy clinical trials targeting inflammation and regenerative medicine.

Victoria is perfectly placed to deliver a cell therapy treatment for COVID-19, A/Prof Lim said.

However, the trial requires funding.

The other trials using our cell-based therapies are in

Originally posted here:
Cell therapies trial planned for COVID-19 - Mirage News

Each week, HealthDay's Physician's Briefing division rounds up the most important COVID-19 developments in the medical field. See this week's edition below for April 20-April 24.

FDA Warns About Treating COVID-19 With Unproven Drugs

FRIDAY, April 24, 2020 (HealthDay News) -- Malaria drugs touted by some as potential "game changers" against COVID-19 are actually too dangerous for general use, the U.S. Food and Drug Administration warned Americans on Friday.

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Premature Posting of Remdesivir Findings Were 'Inconclusive'

FRIDAY, April 24, 2020 (HealthDay News) -- Inconclusive findings from a study investigating the antiviral drug remdesivir as a treatment for COVID-19 were posted to the World Health Organization website "prematurely," drug maker Gilead Sciences said Thursday.

Read Full Article

HTN, Obesity, Diabetes Common in U.S. COVID-19 Patients

FRIDAY, April 24, 2020 (HealthDay News) -- The most common comorbidities among patients hospitalized with COVID-19 in the New York City area are hypertension, obesity, and diabetes, according to a study published online April 22 in the Journal of the American Medical Association.

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Americans Report Concerns Over Their Mental Health During Pandemic

FRIDAY, April 24, 2020 (HealthDay News) -- Mental health concerns top economic worries during the COVID-19 pandemic, according to the results of a survey released by the University of Phoenix.

Read Full Article

COVID-19-Linked Changes Reported in Rheumatic Disease Patient Care

FRIDAY, April 24, 2020 (HealthDay News) -- Changes to health care have been reported among patients with rheumatic diseases during the COVID-19 pandemic, according to a study published online April 20 in ACR: Open Rheumatology.

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More Than One in Five Children in Home Confinement Report Depression

FRIDAY, April 24, 2020 (HealthDay News) -- During the COVID-19 outbreak in Hubei province in China, 22.6 percent of children in home confinement reported depressive symptoms, according to a research letter published online April 24 in JAMA Pediatrics.

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SARS-CoV-2 Stays in Respiratory Samples Longer in Severely Ill

FRIDAY, April 24, 2020 (HealthDay News) -- The median duration of severe acute respiratory syndrome coronavirus 2 RNA is significantly longer in the respiratory samples of patients with severe versus mild disease, according to a study published online April 21 in The BMJ.

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COVID-19 Outcomes Worse With Diabetes, Hyperglycemia

FRIDAY, April 24, 2020 (HealthDay News) -- Diabetes and/or uncontrolled hyperglycemia occur frequently among hospitalized patients with COVID-19 and are associated with worse outcomes, according to a study accepted for publication in the Journal of Diabetes Science and Technology.

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Survey Finds Anesthesiologists Prepared for COVID-19 Patients

FRIDAY, April 24, 2020 (HealthDay News) -- Anesthesiologists on the front lines of treating surgical COVID-19 patients in Turkey are generally knowledgeable about airway management, according to the results of a national survey published online April 6 in Surgical Infections.

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'Health Force' to Combat Pandemic Proposed by U.S. Senators

THURSDAY, April 23, 2020 (HealthDay News) -- A bill to create a "Health Force" to help combat the U.S. COVID-19 outbreak has been announced by two Democratic senators.

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White House Announces Payment Plan for Uninsured COVID-19 Patients

THURSDAY, April 23, 2020 (HealthDay News) -- A plan to begin paying hospitals and doctors who treat uninsured COVID-19 patients was announced by U.S. Health and Human Services Secretary Alex Azar on Wednesday.

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SARS-CoV-2 Can Spread Rapidly in Homeless Shelters

THURSDAY, April 23, 2020 (HealthDay News) -- Severe acute respiratory syndrome coronavirus 2 can spread rapidly in homeless shelters, according to two studies published in the April 22 early-release issue of the U.S. Centers for Disease Control and Prevention Morbidity and Mortality Weekly Report.

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CDC: More Chemical Exposures Reported in January to March 2020

THURSDAY, April 23, 2020 (HealthDay News) -- In January to March 2020, there were more chemical exposures reported to the National Poison Data System than in the corresponding months of 2019 and 2018, according to research published in the April 20 early-release issue of the U.S. Centers for Disease Control and Prevention Morbidity and Mortality Weekly Report.

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ACEIs/ARBs Not Linked to Severity or Mortality of COVID-19

THURSDAY, April 23, 2020 (HealthDay News) -- For patients with hypertension hospitalized with COVID-19 infections, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers are not associated with the severity or mortality of COVID-19, according to a brief report published online April 23 in JAMA Cardiology.

Read Full Article

Mild, No Symptoms Seen for Most Children With SARS-CoV-2 Infection

THURSDAY, April 23, 2020 (HealthDay News) -- Most children with severe acute respiratory syndrome coronavirus 2 infection have mild respiratory symptoms or are asymptomatic, according to a review published online April 22 in JAMA Pediatrics.

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AAD Establishes Registry for Skin Manifestations of COVID-19

THURSDAY, April 23, 2020 (HealthDay News) -- A registry has been created for reporting skin manifestations of COVID-19 following reports of patients presenting with skin conditions, including findings outlined in a letter to the editor published online March 26 in the Journal of the European Academy of Dermatology and Venereology.

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Lopinavir/Ritonavir, Umifenovir Ineffective for Mild COVID-19

THURSDAY, April 23, 2020 (HealthDay News) -- For patients hospitalized with mild/moderate COVID-19, lopinavir/ritonavir or umifenovir monotherapy offers little benefit, according to a study published online April 17 in Med.

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Rapid COVID-19 Test Can Produce False Negatives

WEDNESDAY, April 22, 2020 (HealthDay News) -- A widely used rapid COVID-19 test can produce false negatives if a certain solution is used to move or store patients' samples, the test's maker said.

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Expert Panel: There Are No Proven Drug Treatments for COVID-19

WEDNESDAY, April 22, 2020 (HealthDay News) -- There is no proven drug treatment for COVID-19 patients, according to a panel of experts convened by the U.S. National Institute of Allergy and Infectious Diseases.

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Hydroxychloroquine Seems Not to Cut Ventilator Use in COVID-19

WEDNESDAY, April 22, 2020 (HealthDay News) -- There is no evidence that use of hydroxychloroquine alone or with azithromycin reduces the risks for mechanical ventilation or death from any cause in patients hospitalized with COVID-19, according to a study that has not yet been peer reviewed and was posted online April 21 at medRxiv.org.

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ST-Segment Elevation Described in Patients With COVID-19

WEDNESDAY, April 22, 2020 (HealthDay News) -- For patients with COVID-19 who have ST-segment elevation, indicating potential acute myocardial infarction, there is considerable variability in presentation, and prognosis is poor, according to a letter to the editor published online April 17 in the New England Journal of Medicine.

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Obesity Ups Risk for COVID-19 Severity

WEDNESDAY, April 22, 2020 (HealthDay News) -- There is a high frequency of obesity among patients admitted to intensive care for severe acute respiratory syndrome coronavirus 2, according to a study published online April 9 in Obesity.

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Scoring System Helps Guide Surgical Care During COVID-19

WEDNESDAY, April 22, 2020 (HealthDay News) -- A scoring system for medically necessary time-sensitive procedures can facilitate decision making and triage in the setting of COVID-19, according to a study published online April 9 in the Journal of the American College of Surgeons.

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LA County COVID-19 Infections Far Exceed Number of Confirmed Cases

TUESDAY, April 21, 2020 (HealthDay News) -- An early analysis of antibody testing from Los Angeles County reveals a COVID-19 infection rate that is up to 55 times the number of confirmed COVID-19 cases.

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FDA Authorizes COVID-19 Test That Uses Samples Collected at Home

TUESDAY, April 21, 2020 (HealthDay News) -- The U.S. Food and Drug Administration has approved emergency use of the first COVID-19 test that enables patients to take samples at home.

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Mental Health Consequences of COVID-19 Pandemic Explored

TUESDAY, April 21, 2020 (HealthDay News) -- A new position paper, published online April 15 in The Lancet Psychiatry, highlights the mental health consequences of COVID-19 management.

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COVID-19 Tied to Unique Nasal Symptoms

TUESDAY, April 21, 2020 (HealthDay News) -- COVID-19 is not associated with the symptoms typically associated with a viral cold or allergies, such as nasal blockage or mucus production, according to a review published online April 10 in Laryngoscope Investigative Otolaryngology.

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Expanding Symptom Screening Criteria Can Up COVID-19 Detection

TUESDAY, April 21, 2020 (HealthDay News) -- Expanding COVID-19 symptom screening criteria to include myalgias and chills could identify more health care personnel with the illness, according to a research letter published online April 17 in the Journal of the American Medical Association.

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176,190 U.S. Children Estimated to Have SARS-CoV-2 by April 6, 2020

TUESDAY, April 21, 2020 (HealthDay News) -- About 176,190 children nationwide were estimated to be infected with severe acute respiratory syndrome coronavirus 2 by April 6, 2020, according to a study published online April 16 in the Journal of Public Health Management & Practice.

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Coinfection With SARS-CoV-2, Other Respiratory Pathogens ID'd

TUESDAY, April 21, 2020 (HealthDay News) -- About 20 percent of specimens positive for severe acute respiratory syndrome coronavirus 2 infection are positive for other respiratory pathogens, according to a research letter published online April 15 in the Journal of the American Medical Association.

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Cardiac Cath Lab STEMI Activations Drop During Pandemic

TUESDAY, April 21, 2020 (HealthDay News) -- During the COVID-19 pandemic, there has been a 38 percent reduction in U.S. cardiac catheterization laboratory ST-segment elevation myocardial infarction activations, according to a research letter published online April 10 in the Journal of the American College of Cariology.

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Lab Protocol Failures Led to Ineffective COVID-19 Tests From CDC

MONDAY, April 20, 2020 (HealthDay News) -- The first COVID-19 tests in the United States were ineffective due to poor laboratory practices at the U.S. Centers for Disease Control and Prevention, the U.S. Food and Drug Administration said.

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Public Health Measures Cut COVID-19 Transmission in Hong Kong

MONDAY, April 20, 2020 (HealthDay News) -- Public health measures implemented to suppress local transmission of COVID-19 in Hong Kong were associated with reduced transmission of COVID-19 and influenza, according to a study published online April 17 in The Lancet Public Health.

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New Study Finds That Wearing Contact Lenses Doesn't Increase Risk of COVID-19 Infection - HealthDay Coronavirus Liveblog

Israeli-based Pluristem has treated its first American patient suffering from COVID-19 complications under the countrys compassionate use program.The news comes days after a report by the company showed that six critically ill coronavirus patients in Israel who are considered high-risk for mortality were treated with Pluristems placenta-based cell-therapy product and survived, according to preliminary data provided by the Haifa-based company.In the US case, the patient was treated with the companys PLX cell therapy at Holy Name Medical Center in New Jersey, where Pluristem is already running a Phase III critical limb ischemia study. Like the patients treated in Israel, this patient was critically ill with respiratory failure due to acute respiratory distress syndrome and was intubated in an intensive care unit for three weeks.The companys president and CEO, Yaky Yanay, said that although Pluristem is focused on a planned multinational clinical trial for the treatment of complications associated with coronavirus, it does hope to expand treatment under compassionate use in other countries at the same time.

Specifically, the US treatment was administered under the US Food and Drug Administrations Single Patient Expanded Access Program, which is part of the US Coronavirus Treatment Acceleration Program - an emergency program aimed at getting treatments to corona patients as quickly as possible.

In Israel, the six patients were treated at three different Israeli medical centers for one week, also under a compassionate use program. They were suffering from acute respiratory failure and inflammatory complications associated with COVID-19. Four of the six patients also demonstrated failure of other organ systems, including cardiovascular and kidney failure.

Pluristems PLX cells are allogeneic mesenchymal-like cells that have immunomodulatory properties, meaning they induce the immune systems natural regulatory T cells and M2 macrophages, the company explained in a previous release. The result could be the reversal of dangerous overactivation of the immune system. This would likely reduce the fatal symptoms of pneumonia and pneumonitis (general inflammation of lung tissue).

Previous preclinical findings regarding PLX cells revealed significant therapeutic effects in animal studies of pulmonary hypertension, lung fibrosis, acute kidney injury and gastrointestinal injury.

We are pleased with this initial outcome of the compassionate use program and committed to harnessing PLX cells for the benefit of patients and healthcare systems, Yanay said.

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Israeli COVID-19 treatment with 100% survival rate tested on US patient - The Jerusalem Post