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

News
Article

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

FDA

FDA

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

References

  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
Related Videos
C. Ola Landgren, MD, PhD
Muhamed Baljevic, MD, FACP
Muhamed Baljevic, MD
Sundar Jagannath, MBBS
S. Vincent Rajkumar, MD
Muhamed Baljevic, MD
Sundar Jagannath, MBBS
Sundar Jagannath, MBBS
James Ignatz-Hoover, MD, PhD
Sundar Jagannath, MBBS