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


P-BCMA-ALLO1 was granted an FDA orphan drug designation for the treatment of patients with relapsed/refractory multiple myeloma and is being evaluated in a phase 1 trial.

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  • P-BCMA-ALLO1 for relapsed/refractory multiple myeloma received orphan drug designation from the FDA.
  • Results from a phase 1 trial (NCT04960579) show that P-BCMA-ALLO1 was well-tolerated with manageable adverse effects and no graft-vs-host disease (GVHD) observed.
  • The treatment also demonstrated promising effectiveness with a high objective response rate (ORR) among patients.

The FDA has granted an orphan drug designation to P-BCMA-ALLO1, a novel BCMA-targeted allogeneic, T stem cell memory (TSCM)-rich chimeric antigen receptor (CAR) T-cell therapy for the treatment of relapsed/refractory multiple myeloma.1

This designation highlights the unmet medical need for this type of treatment and provides potential benefits during development.

Findings from a phase 1 trial of P-BCMA-ALLO1 support this regulatory decision. In the intent-to-treat (ITT) population of the study, all patients were given P-BCMA-ALLO1 without the use of bridging chemotherapy or other antimyeloma bridging therapies.1 According to preliminary safety and efficacy data, P-BCMA-ALLO1 was well tolerated and had a favorable safety profile with no GVHD seen among patients treated at any dose. Additionally, only low rates of grade 1/2 cytokine release syndrome and neurotoxicity were seen among all evaluable patients.2

The study also showed allogeneic TSCM-rich CAR T cells to be successfully trafficked to bone marrow and differentiated into effector T cells, which lasted for at least 6 weeks after treatment.

“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,” said Kristin Yarema, PhD, president and chief executive officer of Poseida Therapeutics, in the press release.1 “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.”

Data from a subset of recently enrolled patients refractory to initial BCMA-targeting therapy are expected to be shared at the 2024 American Association for Cancer Research Annual Meeting. Clinical updates on the P-BCMA-ALLO1 program also are planned to be shared at a scientific meeting in the second half of 2024.

About the Phase 1 Study of P-BCMA-ALLO1

CAR T-cell therapy in multiple myeloma: © Kasloom - stock.adobe.com

CAR T-cell therapy in multiple myeloma: © Kasloom - stock.adobe.com

In the phase 1, ongoing, multicenter, open-label, dose-escalation study, investigators are assessing P-BCMA-ALLO1 for the treatment of patients 18 years of age or older with multiple myeloma that was relapsed/refractory to prior treatment with a proteasome inhibitor, immunomodulatory agent, and anti-CD38 therapy.2,3 Patients are currently being recruited, and the study has an estimated primary completion date of December 2027.

Patients with prior exposure to a BCMA-targeted therapy, including autologous BCMA CAR T and bispecific T cell-engaging antibodies, were eligible to enroll in the trial, and patients must have been at least 90 days out from their last autologous stem cell transplant, if performed. Moreover, measurable myeloma, adequate vital organ function, and an ECOG performance status of 0 to 1 were required, and all patients must have recovered from toxicities due to prior therapies.

In phase 1 of the study, there are 2 parts. The first (part 1) is a weight-based dose-escalation following a 3+3 design of dose-escalating cohorts. Part 2 of the study includes administration of the agent at fixed doses.

Once enrolled and following lymphodepletion, patients underwent P-BCMA-ALLO1 infusion, which occurred within a median of 7 days after enrollment.2 Six cohorts were included in the study and patients were treated with 1 of 3 fludarabine/cyclophosphamide lymphodepletion regimens, including 3 days of fludarabine at 30 mg/m2 per day for all patients and, which depended 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.

Safety and maximum tolerated dose of P-BCMA-ALLO1 were the primary end points of the study. The secondary end points included ORR, duration of response, time to response, progression-free survival, and overall survival.

According to findings presented at the 2023 American Society of Hematology Annual Meeting, 39 patients were enrolled as an ITT population as of the data cutoff of October 23, 2023.2 A total of 82% of patients in the pooled part 1 and part 2 arms (n = 11) achieved an ORR. Among the 6 patients in the part 2 arm, the ORR was 83%, and 100% of responding patients had a very good partial response (VGPR) or better. Further, 40% of patients in the part 2 arm achieved a stringent complete response. In the part 1 arm, which consisted of 5 patients, the ORR was 80%. Fifty percent of the patients who responded achieved a VGPR.

Across both arms, patients who were not previously exposed to a prior BCMA-targeting bispecific antibody (n = 9) achieved an ORR of 100%. Patients treated with a previous autologous CAR T BCMA-targeted therapy also had an ORR of 100%.

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 18, 2024. https://tinyurl.com/4fpj4s5x
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 18, 2024. https://tinyurl.com/w7hjyszh
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 18, 2024. https://clinicaltrials.gov/study/NCT04960579
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