Investigators saw a 91% overall response rate (ORR) in patients with relapsed/refractory multiple myeloma (RRMM) following treatment with allogeneic CAR-T therapy P-BCMA-ALLO1 and lymphodepletion.

The interim data from an ongoing Phase I trial in patients who have previously received three or more prior lines of therapy were presented at the 21st International Myeloma Society (IMS) Annual Meeting in Rio de Janeiro.

The Arm C data also showed a 100% ORR in BCMA-naïve patients, and an 86% ORR in those who had received at least one prior BCMA- and/or GPRC5D-targeting treatment modality.

P-BCMA-ALLO1 is an investigational non-viral, stem cell memory T cell (TSCM)-rich allogeneic CAR-T cell therapy. The therapy is being developed by Poseida Therapeutics and Roche as part of a broader collaboration focused on blood cancers.

It was recently granted Regenerative Medicine Advanced Therapy (RMAT) designation from the FDA.

“The high overall response rate of 91% is remarkable because most study participants in my centre had rapidly proliferative refractory disease, in contrast with those treated in the pivotal clinical trials of FDA-approved autologous CAR-T therapies. Such patients treated in the current trial of P-BCMA ALLO1 would not have qualified for standard of care autologous CAR-T therapy,” said Bhagirathbhai Dholaria, Associate Professor of Medicine, Malignant Hematology & Stem Cell Transplantation at Vanderbilt University Medical Center in Nashville, Tennessee, and trial investigator.

“All patients in the Phase I trial have been treated quickly once enrolled, with no waiting for manufacturing, with no need for apheresis or bridging therapy, demonstrating key advantages of allogeneic CAR-T cell therapy.”

Good results in a pretreated population

The ORR across all four study arms was 54%; 11% of patients achieved a complete response (CR) or a stringent complete response (sCR), and 33% achieved a very good partial response or higher (VGPR+).

The median duration of response (DoR) was 232 days for study Arms A and B – the cohorts with six or more months of follow-up at the time of data cut-off.

P-BCMA-ALLO1 levels measured in the peripheral blood and were much higher in patients in Arm C (cyclophosphamide 750mg/m2/day) and Arm B (cyclophosphamide 1000mg/m2/day) than in patients in Arm S (cyclophosphamide 300mg/m2/day), and Arm A (cyclophosphamide 500mg/m2/day).

Arm C was identified as the optimised lymphodepletion arm based on cellular kinetics, safety and efficacy.

“P-BCMA-ALLO1 is one of the most advanced allogeneic CAR-T in clinical development for multiple myeloma, manufactured using non-viral technology to produce a TSCM-rich therapy that has shown a compelling emerging product profile,” said Kristin Yarema, President and Chief Executive Officer of Poseida Therapeutics. “We are encouraged to see such a high overall response rate in an arm of the Phase I trial with optimised lymphodepletion, along with standout safety results across all arms, given that the study population was heavily pretreated, high-risk, and in general had many features that historically have led to a poor prognosis.”

Diana Spencer, Senior Digital Content Editor, DDW