FDA Grants Orphan Drug Designation to P-BCMA-ALLO1 in R/R Multiple Myeloma


P-BCMA-ALLO1 has been granted orphan drug designation by the FDA for the treatment of patients with relapsed/refractory multiple myeloma.



The FDA has granted orphan drug designation to the novel BCMA-targeted allogeneic, T stem cell memory (TSCM)-rich CAR T-cell therapy P-BCMA-ALLO1 as a potential therapeutic option for patients with relapsed/refractory multiple myeloma, according to an announcement by Poseida Therapeutics.1

Preliminary safety and efficacy data from a phase 1 trial (NCT04960579) of P-BCMA-ALLO1 were shared at the 2023 ASH Annual Meeting. P-BCMA-ALLO1 was shown to be well tolerated with a favorable safety profile.1 No graft-vs-host disease at any dose was observed, and there were low rates of grade 1/2 cytokine release syndrome and neurotoxicity among all evaluable patients.2

All patients in the intent-to-treat (ITT) population received this therapy without the use of bridging chemotherapy or other antimyeloma bridging therapies.1 Moreover, data demonstrated that allogeneic TSCM-rich CAR T cells were successfully trafficked to bone marrow, differentiated into effector T cells, and persisted for at least 6 weeks after treatment. These data support the hypothesis of cell persistence at tumor-relevant sites, as well as the potential utility of TSCM-rich allogeneic CAR T-cell therapy in multiple myeloma.

The agent is being developed by Poseida Therapeutics in partnership with Roche. Investigators plan to present data from a subset of recently enrolled patients refractory to initial BCMA-targeting therapy at the 2024 AACR Annual Meeting. Additional clinical updates on the P-BCMA-ALLO1 program are anticipated at a scientific meeting in the second half of 2024, subject to coordination with Roche.

“The orphan drug designation for P-BCMA-ALLO1 underscores the high unmet medical need for a rapid and accessible off-the-shelf allogeneic CAR T therapy for patients with multiple myeloma,” Kristin Yarema, PhD, president and chief executive officer of Poseida Therapeutics, stated in the news release. “This designation further validates our belief that TSCM-rich allogeneic CAR T therapies may potentially offer the optimal combination of clinical results, on-demand availability, and high-volume production, while supporting broader access to CAR T therapies. We look forward to continuing our work on the phase 1 study of P-BCMA-ALLO1 and plan to share further clinical updates in 2024.”

The ongoing, multicenter, open-label, dose-escalation study included patients 18 years of age or older with a confirmed diagnosis of multiple myeloma that was relapsed/refractory to prior treatment with a proteasome inhibitor, immunomodulatory agent, and anti-CD38 therapy.2,3 Notably, previous exposure to a BCMA-targeted therapy, including autologous BCMA CAR T and bispecific T cell–engaging antibodies, was allowed.3 Patients were also required to be at least 90 days out from their last autologous stem cell transplant, if performed; have adequate vital organ function; have recovered from toxicities due to prior therapies; and have an ECOG performance status of 0 to 1.

Following lymphodepletion, all enrolled patients underwent P-BCMA-ALLO1 infusion within a median of 7 days after enrollment.2 Patients were divided into 6 cohorts and received 1 of 3 fludarabine/cyclophosphamide lymphodepletion regimens. These regimens consisted of 3 days of fludarabine at 30 mg/m2 per day for all patients and, depending on the cohort, 3 days of cyclophosphamide at 300 mg/m2, 500 mg/m2, or 1000 mg/m2 per day, followed by infusion of P-BCMA-ALLO1 cells at doses up to 6 x 106 cells/kg.

The primary end points of the phase 1 study were the safety and maximum tolerated dose of P-BCMA-ALLO1 through assessment of dose-limiting toxicities and adverse effects.3Key secondary end points evaluating the anti-myeloma effect of P-BCMA-ALLO1 included objective response rate (ORR), duration of response, time to response, progression-free survival, and overall survival.

At the data cutoff of October 23, 2023, 39 patients were enrolled as an ITT population.2 Most of the 33 evaluable patients with at least 4 weeks of follow-up had received a median of 7 prior lines of therapy and 30% had high-risk disease by cytogenetics. Approximately 39% of patients had received previous BCMA-targeted therapy. Notably, 11 patients were in the 2 cohorts receiving 2 x 106 cells/kg of P-BCMA-ALLO1 and higher cyclophosphamide preconditioning doses at either 500 mg/m2 (part 1 arm) or 1000 mg/m2 (part 2 arm).

Additional efficacy findings from the study showed that 82% of patients in the pooled part 1 and part 2 arms (n = 11) achieved an ORR. In the part 2 arm (n = 6), the ORR was 83%, with 100% of responding patients achieving a very good partial response (VGPR) or better and 40% achieving a stringent complete response. In the part 1 arm (n = 5), the ORR was 80%, and 50% of responding patients achieved a VGPR. Notably, patients across both arms who had not been previously exposed to a prior BCMA-targeting bispecific antibody (n = 9) achieved an ORR of 100%, as did patients who had received prior autologous CAR T BCMA-targeted therapy.

The phase 1 trial is currently recruiting patients and has an estimated primary completion date of December 2027.3


  1. Poseida Therapeutics announces FDA orphan drug designation granted to P-BCMA-ALLO1 for the treatment of multiple myeloma. News release. Poseida Therapeutics. March 13, 2024. Accessed March 14, 2024. https://investors.poseida.com/news-releases/news-release-details/poseida-therapeutics-announces-fda-orphan-drug-designation
  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 March 14, 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 February 29, 2024. Accessed March 14, 2024. https://clinicaltrials.gov/study/NCT04960579
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