StemCell Therapy

Karyopharm Doses First Patient in Brain Cancer Trial

Karyopharm Therapeutics (KPTI) announced that it has dosed the first patient for its Phase 1/2 clinical trial. The study aims to assess the potential of oral Selinexor in combination with standard of care therapy in treating patients suffering from newly diagnosed or recurrent glioblastoma. This multi-site study is expected to enroll nearly 400 patients in clinical sites spread across the United States, Europe and Israel.

The randomized Phase 1/2 study is scheduled to be conducted in two phases. The Phase 1 study is mainly aimed at determining dosage, while the Phase 2 randomized efficacy exploration trial aims to independently assess three different combination regimens in three treatment arms in patients with newly diagnosed GBM (Arms A and B) or with recurrent GBM (Arm C). Arms A and B will examine Selinexor in conjunction with radiation therapy with or without temozolomide. Arm C aims to assess the potential of Selinexor and lomustine.

The primary endpoint of the Phase 1 study is to determine the maximum tolerated dose and the recommended dose to be given in the second phase trial. Sharon Shacham, PhD, MBA, President and Chief Scientific Officer of Karyopharm, said, While selinexor has been most extensively studied in patients with hematologic malignancies, there is increasing evidence that selinexor may also play an important role in the treatment of a variety of solid tumors, including patients with GBM. Phase 2 study will have the primary endpoints of progression-free survival in patients with newly diagnosed GBM and overall survival (OS) in patients with recurrent GBM.

Selinexor is an oral selective inhibitor of the nuclear export (SINE) compound. The compound is known to block the cellular protein XP01, which plays an important role in controlling various tumor suppressor proteins as well as other relevant oncoproteins. In its previous studies, the drug candidate has shown the ability to cross the blood-brain barrier. In a Phase 2 KING study, aimed to assess Selinexor as a single agent in patients with recurrent GBM, it showed robust anti-cancer activity.

Selinexor is already approved by the FDA as a treatment for patients with relapsed or refractory multiple myeloma. It is currently the only FDA-approved XP01 inhibitor and has two additional supplemental New Drug Applications under review by the FDA. The first application seeks label extension for the drug candidate to include its use in treating patients with multiple myeloma after at least one prior line of therapy. The second application pertains to the treatment of patients suffering from relapsed or refractory diffuse large B-cell lymphoma. The drug candidate is in the market under the brand name XPOVIO.

Karyopharm mainly focuses on developing therapies for treating different cancers and other major diseases.

Dynavax (DVAX) announced that it has completed the process of enrolment for its Heplisav-B Phase 1 clinical trial. The company expects the final immunogenicity data to be available by Q4. Dynavax has enrolled 119 patients for the study, which aims to evaluate the drug candidate in adult patients suffering from end-stage renal disease who are starting or already undergoing hemodialysis.

HBV-24 is an open-label, single-arm study which is designed to evaluate a new 4-dose regimen of HEPLISAV-B. The patients enrolled in the study have not previously been treated with a hepatitis B vaccine. Robert Janssen, MD, Chief Medical Officer at Dynavax. We are evaluating a 4-dose regimen of HEPLISAV-B in this study, which we believe may provide an important hepatitis B vaccination alternative for adults with end-stage renal disease on dialysis. We look forward to a scientific presentation of the final data at an appropriate forum in the future. Hepatitis B is a viral disease of the liver and may lead to other complications such as liver cancer and cirrhosis.

The trial aims to assess the drug candidates immunogenicity at study week 20 and safety over the 68-week study duration. Safety and effectiveness of HEPLISAV-B have yet to be established in adults on hemodialysis. The hepatitis B virus is highly infectious, and there is no cure for this. However, the disease may be prevented by effective vaccination. Adults may contract the infection through various means, including infected blood transfusion.

HEPLISAV-B combines hepatitis B surface antigen with Dynavaxs proprietary Toll-like Receptor (TLR) 9 agonist CpG 1018. The drug candidate works by boosting the immune response in a patient. It is indicated for preventing infection caused by all known subtypes of hepatitis virus. HEPLISAV-B is currently only prescribed to adults 18 years or older.

BeyondSpring (BYSI) reported positive data from its PROTECTIVE-2 Phase 2 superiority trial. The study aims to test the potential of Plinabulin, the companys lead drug candidate, in treating breast cancer.

PROTECTIVE-2 assessed the superiority potential of the drug candidate in preventing chemotherapy-induced neutropenia in breast cancer patients treated with docetaxel, doxorubicin and cyclophosphamide. The patients were administered 20mg/m2 of Plinabulin combined with 6mg of Neulasta. The control group was given 6mg of Neulasta alone. The data showed that the combination improved compliance with targeted chemotherapy. It enabled more patients to take the optimal chemotherapy dose and regimen.

None of the patients in combination group downgraded chemotherapy from the TAC regimen to the TC regimen, whereas 18.2 percent patients in the control cohort had to downgrade. Dr. Ramon Mohanlal, BeyondSprings Chief Medical Officer and EVP, R&D, said, This approach provides potential benefits for both clinicians and patients: clinicians may gain greater control over cancer care, and patients may experience better clinical outcomes and an improved quality of life. The improvement in the prevention of Grade 4 neutropenia that is seen with the Plinabulin-Neulasta combination is even more important in todays healthcare environment due to the devastating impact of COVID-19 on immune-suppressed patients. The company plans to release interim top line data from the Phase 3 trial in the near future.

Plinabulin is a differentiated immune and stem cell modulator. The drug candidate is currently in late-stage clinical development phase for treating cancer and to alleviate chemotherapy-induced neutropenia. The drug mainly acts as an antigen presenting cell inducer and aids T-cell activation. In combination, of Plinabulin and G-CSF play complementary roles in reducing CIN. PROTECTIVE-2 is a superiority study and pits the combination against Neulasta. Apart from Plinabulin, BeyondSpring has three immune-oncology product candidates in its development pipeline. It also has a drug discovery platform which uses the ubiquitination degradation pathway.

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Original post:
Karyopharm Brain Cancer Trial, And Other News: The Good, Bad And Ugly Of Biopharma - Seeking Alpha

This entry was posted on June 16, 2020 at 12:45 pm and is filed under Stem Cell Complications. You can follow any responses to this entry through the RSS 2.0 feed. Both comments and pings are currently closed. |