FDA Grants RMAT Designation to P-BCMA-ALL01 for R/R Multiple Myeloma

FDA

The FDA has granted regenerative medicine advanced therapy (RMAT) designation to P-BCMA-ALL01 for the treatment of patients with relapsed/refractory multiple myeloma.¹

P-BCMA-ALL01 is an investigational stem cell memory T cell–based allogeneic CAR-T cell therapy currently being evaluated in a phase 1/1b trial (NCT04960579) in patients with relapsed/refractory myeloma. Prior data presented at the 2023 ASH Annual Meeting showed that among evaluable patients treated with the CAR T-cell therapy at a dose of 2x10⁶ cells/kg and a higher cyclophosphamide preconditioning dose of 500 mg/m² (P1 cohort; n = 5) or 1,000 mg/m² (P2 cohort; n = 6), the overall response rate (ORR) was 82%.² The ORR for the P2 cohort was 83% with 2 patients experiencing a stringent complete response and all 5 responders achieving a very good partial response (VGPR) or better. The ORR in the P1 cohort was 80%, and 2 of the 4 responders had a VGPR or better.

Notably, the ORR was 100% among patients in these 2 cohorts who were naive to a BMCA-directed bispecific antibody (n = 9). In patients who had received a prior BCMA-directed autologous CAR T-cell therapy (n = 2), the ORR was 100%.

Among all evaluable patients treated (n = 33), no instances of graft-vs-host disease were reported. P-BCMA-ALL01 was associated with low rates of cytokine release syndrome (CRS) and neurotoxicity, which were all grade 2 or less.

“The RMAT designation for P-BCMA-ALLO1, our lead program, is based on impressive early clinical data from our ongoing phase 1 study and further validates its potential to address the unmet needs of patients with relapsed/refractory multiple myeloma," Kristin Yarema, PhD, president and chief executive officer of Poseida Therapeutics, stated in a news release.1 “Importantly, our data has shown clinical responses in very sick, refractory patients, including those that have received prior BCMA-targeted therapies. With both RMAT and orphan drug designations for P-BCMA-ALLO1, we look forward to working closely with the FDA as we continue to advance this next-generation, off-the shelf allogeneic [CAR T-cell] therapy, including the recently initiated phase 1b portion of the trial.”

The open-label, phase 1/1b study is enrolling patients at least 18 years of age with relapsed/refractory multiple myeloma who have received treatment with a proteasome inhibitor, immunomodulatory drug, and anti-CD38 monoclonal antibody.³ At least 90 days must have passed prior to enrollment for patients who have undergone a prior autologous stem cell transplant. Resolution of toxicities from prior therapies, an ECOG performance status of 0 to 1, and adequate organ function are also required for enrollment.

Key exclusion criteria consist of active hemolytic anemia, plasma cell leukemia, Waldenström macroglobulinemia, POEMS syndrome, disseminated intravascular coagulation, leukostasis, or amyloidosis; an active second malignancy, other than low-risk neoplasms such as non-metastatic basal cell or squamous cell skin carcinoma; active autoimmune disease; a history of significant central nervous system disease; and prior allogeneic cellular therapy or gene therapy.

Phase 1 featured 6 cohorts that ranged in size from 1 to 6 patients each, where patients received lymphodepletion consisting of 3 days of fludarabine at 30 mg/m2 for all patients plus 3 days of cyclophosphamide at 300, 500, or 1,000 mg/m2. P-BCMA-ALL01 was then infused at a dose of up to 6x106cells/kg.²

The study’s primary end points are the rate of dose-limiting toxicities in part 1 of phase 1, the frequency and severity of adverse effects—including CRS—in part 2 of phase 1, and the determination of the recommended phase 2 dose in phase 1b.³ Efficacy and safety are secondary end points.

Among evaluable patients already treated during the study, the median number of prior lines of therapy was 7. Thirty percent of patients had high-risk disease by cytogenetics, and 39% received prior BCMA-targeted therapy.²

Additional data will be presented at the 2024 International Myeloma Society Annual Meeting in September.¹

References

1. Poseida Therapeutics receives regenerative medicine advanced therapy (RMAT) designation from FDA for P-BCMA-ALLO1 to treat relapsed/refractory multiple myeloma. News release. Poseida Therapeutics. September 16, 2024. Accessed September 16, 2024. https://investors.poseida.com/news-releases/news-release-details/poseida-therapeutics-receives-regenerative-medicine-advanced-0
2. Poseida Therapeutics presents positive early results from its phase 1 trial of allogeneic CAR-T P-BCMA-ALLO1 in relapsed-refractory multiple myeloma at the 65th American Society of Hematology (ASH) Annual Meeting. News release. Poseida Therapeutics. December 10, 2023. Accessed September 16, 2024. https://investors.poseida.com/news-releases/news-release-details/poseida-therapeutics-presents-positive-early-results-its-phase-1
3. P-BCMA-ALLO1 allogeneic CAR-T cells in the treatment of subjects with multiple myeloma (MM). ClinicalTrials.gov. Updated August 27, 2024. Accessed September 16, 2024. https://clinicaltrials.gov/study/NCT04960579