StemCell Therapy

CAR-T therapies being developed by Bristol Myers Squibb and Janssen have all hit targets in early-mid-stage trials, raising hopes of new treatment options for difficult to treat blood cancers.

First up, Johnson & Johnsons Janssen unveiled initial results from the Phase Ib/II CARTITUDE-1 study assessing the efficacy and safety of JNJ-68284528 (JNJ-4528) an investigational B cell maturation antigen (BCMA)-directed chimeric antigen receptor T cell (CAR-T) therapy in treating relapsed or refractory multiple myeloma.

The study enrolled patients who have received at least three prior lines of therapy or are double refractory to a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD); have received a PI, IMiD and an anti-CD38 antibody; and who progressed on or within 12 months of their last line of therapy.

Results from the Phase Ib portion of the CARTITUDE-1 study showed early and deep responses among patients (n=29) with a median of five prior multiple myeloma treatment regimens treated with JNJ-4528, with 100 percent of patients achieving a response at a median six-month follow-up, the firm said.

The overall response rate (ORR) included 69% of patients achieving a complete response (CR) or better; 86% of patients achieving a very good partial response (VGPR) or better; and 14% of patients achieving a partial response (PR).

Also key, 100% of evaluable patients achieved early minimal residual disease (MRD)-negative disease status at day 28 post-infusion, while at the six-month follow-up, 27 of 29 patients were progression-free.

The results highlight a compelling clinical profile for the treatment in this setting, said Deepu Madduri, assistant professor of Medicine, Haematology and Medical Oncology, Tisch Cancer Institute at Mount Sinai, New York, and principal study investigator.

US regulators have granted JNJ-4528 a breakthrough designation in the US based on the data.

Liso-cel also on target

Elsewhere, Bristol-Myers Squibb's CAR-T cell therapy liso-cel (lisocabtagene maraleucel) showed promise across two trials involving patients with blood cancers.

The studies included an evaluation of liso-cel in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) (TRANSCEND CLL 004); and a study in second-line patients with relapsed or refractory large B-cell non-Hodgkins lymphoma (NHL) patients who were ineligible for high-dose chemotherapy and hematopoietic stem cell transplant (PILOT).

The Phase II PILOT assessed the CAR-T therapy in patients with relapsed/refractory large B-cell NHL who had received only one prior line of immunochemotherapy and were deemed ineligible for HSCT due to patient factors including age, comorbidities or performance status.

All patients eligible for evaluation achieved a response with six (50%) patients achieving a CR. Seven of 12 (58%) patients maintained response levels at three months following liso-cel infusion.

Of the 13 patients, 61.5% had at least one treatment related side effect of grade 3 or higher and these were primarily cytopenias. Four patients had prolonged grade 3 or higher cytopenias.

The Phase I/II TRANSCEND CLL 004 study included patients who had a median of five prior lines of therapy. All (23/23) had received prior ibrutinib and most (21/23) were refractory to or had relapsed on the BTK inhibitor. There were nine patients (39%) that had failed both a BTK inhibitor and venetoclax, and most (83%) were considered to high-risk features.

The overall response rate (ORR) after median follow-up of 11 months for patients receiving liso-cel was 81.5%, with 45.5% achieving a complete response (CR). In patients that had failed a BTK inhibitor and venetoclax, the ORR was 89% with 67 achieving a CR.

Among 20 patients evaluable for minimal residual disease (MRD), the majority achieved undetectable MRD in the blood (75%) and bone marrow (65%) by next-generation sequencing, the firms noted.

On the safety side, treatment-emergent adverse events (TEAE) of any grade occurred in all patients, with 96% experiencing one classed as a grade 3 or higher, including anemia (78%), thrombocytopenia (70%), neutropenia (56.5%), leukopenia (43.5%), febrile neutropenia (26%), lymphopenia (26%) and cytokine release syndrome (9%).

Also, 74% of patients had cytokine release syndrome (CRS) of any grade with 9% of patients experiencing grade 3 CRS. Thirty-nine percent had neurological events of any grade, while 22% had grade 3 or higher.

As we continue to evaluate liso-cel in important new disease settings and areas of unmet medical need, we are encouraged to see the early results from these studies, said Stanley Frankel, senior vice president, Cellular Therapy Development for BMS.

Data from all studies were presented at the American Society of Hematology (ASH) Annual Meeting in Orlando, Florida.

The rest is here:
CAR-T therapies shine at ASH - PharmaTimes

This entry was posted on December 11, 2019 at 10:42 am and is filed under Stem Cell Negative. You can follow any responses to this entry through the RSS 2.0 feed. Both comments and pings are currently closed. |