Poseida Therapeutics Announces Positive Interim Phase 1 Results for P-BCMA-ALLO1 in Relapsed/Refractory Multiple Myeloma

Poseida Therapeutics, Inc., a clinical-stage biopharmaceutical company, has unveiled new interim results from its ongoing Phase 1 trial of P-BCMA-ALLO1 in patients with relapsed/refractory multiple myeloma (RRMM). The data was presented at the 21st International Myeloma Society (IMS) Annual Meeting in Rio de Janeiro. These findings show a promising overall response rate (ORR) of 91% in Arm C, which involved an optimized lymphodepletion strategy, and notable safety outcomes among the 23 heavily pretreated patients.

P-BCMA-ALLO1 is an investigational allogeneic CAR-T cell therapy, rich in stem cell memory T cells (TSCM). Currently in Phase 1/1b clinical development, it aims to treat RRMM patients. Poseida is developing this off-the-shelf therapy in collaboration with Roche, focusing on blood cancers using Poseida's TSCM-rich CAR-T platform. The trial's compelling results reveal that P-BCMA-ALLO1 achieved a 91% ORR, including a 100% ORR in BCMA-naïve patients and an 86% ORR in those who had prior BCMA and/or GPRC5D targeting treatments.

The ongoing Phase 1/1b trial is designed to evaluate the safety and maximum tolerated dose (primary objective) and anti-myeloma activity (secondary objective) of P-BCMA-ALLO1. As of September 6, 2024, 72 patients were enrolled across four different study arms, each with varying doses and lymphodepletion regimens. Notably, 43% of participants had received prior BCMA and/or GPRC5D targeting therapies, including autologous CAR-T and T-cell engagers.

Patients in the intent-to-treat (ITT) population were rapidly treated, with a median time of one day from enrollment to the start of treatment. There were no requirements for anti-myeloma bridging therapies or invasive procedures like apheresis, highlighting the efficiency of this allogeneic CAR-T approach. The ORR across all study arms was 54%, with 11% achieving complete or stringent complete responses (CR/sCR) and 33% achieving very good partial responses or higher (VGPR+). The median duration of response (DoR) was 232 days in Arms A and B.

The study identified Arm C as the optimized lymphodepletion arm due to superior cellular kinetics, safety, and efficacy. In Arm C, 23 patients received cyclophosphamide and fludarabine along with approximately 2x10^6 cells/kg of P-BCMA-ALLO1. Remarkably, the ORR in this arm was 91%, with 22% of patients achieving CR or sCR and 48% achieving VGPR+. The median duration of follow-up was less than 3.5 months, making it too early to estimate the median DoR.

Safety outcomes in Arm C were favorable, showing no dose-limiting toxicities or severe cytokine release syndrome (CRS) and immune effector cell neurotoxicity syndrome (ICANS). The incidence of Grade 1 or 2 CRS was 39%, and ICANS was 13%. Additionally, there were no cases of graft-vs-host disease (GvHD) or other severe neurological conditions. The rate of infections was 48%, with most being mild to moderate.

Poseida is now advancing P-BCMA-ALLO1 into the Phase 1b part of the trial, which continues to enroll patients using the optimized lymphodepletion regimen from Arm C. This progression marks a significant step forward in the development of allogeneic CAR-T therapies for multiple myeloma, offering hope to heavily pretreated patients with this challenging condition.

P-BCMA-ALLO1 has been recognized by the FDA with Regenerative Medicine Advanced Therapy (RMAT) designation, further emphasizing its potential in treating relapsed/refractory multiple myeloma. As Poseida continues its clinical trials, the biopharmaceutical community remains hopeful for more breakthroughs in cell therapy and genetic medicine.