Poseida Therapeutics announced positive interim Phase 1 results for its allogeneic CAR-T therapy, P-BCMA-ALLO1, in patients with relapsed/refractory multiple myeloma (RRMM). The data, presented at the 21st International Myeloma Society (IMS) Annual Meeting, showed a 91% overall response rate (ORR) in an optimized lymphodepletion arm, indicating a significant advancement in the treatment of this challenging cancer. The trial enrolled heavily pretreated patients who had received three or more prior lines of therapy.
High Response Rates in Heavily Pretreated Patients
The Phase 1 trial included patients who had previously undergone multiple treatments, including BCMA-targeted therapies. In the optimized lymphodepletion arm (Arm C), patients received cyclophosphamide (750 mg/m2/day) and fludarabine (30 mg/m2/day), followed by P-BCMA-ALLO1 at approximately 2x106 cells/kg. The results demonstrated:
- A 91% ORR across all patients in Arm C.
- A 100% ORR in BCMA-naïve patients.
- An 86% ORR in patients who had received prior BCMA-targeting treatments.
Bhagirathbhai R. Dholaria, M.D., Associate Professor of Medicine at Vanderbilt University Medical Center and trial investigator, noted, "The high overall response rate of 91% is remarkable because most study participants in my center had rapidly proliferative refractory disease... Such patients treated in the current trial of P-BCMA ALLO1 would not have qualified for standard of care autologous CAR T therapy."
Favorable Safety Profile
In addition to the high response rates, P-BCMA-ALLO1 demonstrated a favorable safety profile. Key safety results from Arm C included:
- No dose-limiting toxicities.
- Low incidence of Grade 1 or 2 cytokine release syndrome (CRS) (39%) and immune effector cell neurotoxicity syndrome (ICANS) (13%).
- No Grade 3 or higher CRS or ICANS.
- No graft-versus-host disease (GvHD), hemophagocytic lymphohistiocytosis (HLH), Parkinsonism, or cranial neuropathies.
Advantages of Allogeneic CAR-T Therapy
Unlike autologous CAR-T therapies, P-BCMA-ALLO1 is an allogeneic, or "off-the-shelf," therapy. This means that the CAR-T cells are derived from a healthy donor rather than the patient themselves. This approach offers several potential advantages:
- No waiting time for manufacturing, allowing for quicker treatment initiation.
- No need for apheresis or bridging therapy.
- Potential for broader patient access.
Kristin Yarema, Ph.D., president and chief executive officer of Poseida Therapeutics, stated, "We are encouraged to see such a high overall response rate... 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."
Regulatory Designations and Future Plans
P-BCMA-ALLO1 has been granted Regenerative Medicine Advanced Therapy (RMAT) designation by the FDA, which is intended to expedite the development and review of regenerative medicine therapies for serious or life-threatening diseases. The ongoing Phase 1/1b trial is continuing to enroll patients using the optimized lymphodepletion regimen from Arm C, with dose optimization ongoing.
