FDA Grants P-BCMA-ALLO1 RMAT Designation in R/R Multiple Myeloma

• The FDA has granted regenerative medicine advanced therapy (RMAT) designation to P-BCMA-ALLO1 for the potential treatment of relapsed/refractory (R/R) multiple myeloma.
• P-BCMA-ALLO1 is an investigational stem cell memory T-cell (TSCM)-based allogeneic chimeric antigen receptor (CAR) T-cell therapy.
• The agent is currently in phase 1/1b clinical development (NCT04960579).

The investigational TSCM-based allogeneic CAR T-cell therapy P-BCMA-ALLO1 has been granted RMAT designation from the FDA.¹ The agent is currently in development for the treatment of patients with R/R multiple myeloma.

Early results from an ongoing, phase 1 study of P-BCMA-ALLO1 showed the agent’s potential in offering promising efficacy and safety, as well as quick off-the-shelf patient access. In the study, P-BCMA-ALLO1 was well tolerated and had a favorable safety profile with no graft-vs-host disease (GVHD) seen in any patients treated at any dose. Further, low rates of grade 1/2 cytokine release syndrome and neurotoxicity were seen among all evaluable patients.²

New findings from the phase 1 study of P-BCMA-ALLO1 will be presented at the 21st International Myeloma Society Annual Meeting, and additional results are expected to be released in the second half of 2024.¹

Multiple myeloma cells: © David A Litman - stock.adobe.com

"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," said Kristin Yarema, PhD, president and chief executive officer of Poseida Therapeutics, in a press release. "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 therapy, including the recently initiated phase 1b portion of the trial."

In addition to this RMAT designation for adult patients with R/R multiple myeloma following at least 3 prior lines of therapies, including a proteasome inhibitor, an immunomodulatory agent (IMiD), and anti-CD38 antibody, the FDA also previously granted the agent an orphan drug designation in multiple myeloma.

Overview of the Phase 1 Study Evaluating P-BCMA-ALLO1

P-BCMA-ALLO1 is currently undergoing evaluation in a phase 1, ongoing, multicenter, open-label, dose-escalation study. Enrollment is open to patients aged 18 years and older with prior exposure to a BCMA-targeted therapy, including autologous BCMA CAR T and bispecific T cell-engaging antibodies. Patients are required to be at least 90 days out from their last autologous stem cell transplant, if performed, to be included in the study, and measurable myeloma, adequate vital organ function, and an ECOG performance status of 0 to 1 were also required. Additionally, patients must have recovered from toxicities due to prior therapies.³

The first phase of the study has 2 parts with part 1 being a weight-based dose-escalation following a 3+3 design of dose-escalating cohorts, and part 2 including administration of the agent at fixed doses.

Patients enrolled in the trial underwent P-BCMA-ALLO1 infusion following lymphodepletion. This occurred within a median of 7 days after enrollment.² The study included 6 cohorts.

The primary end points of the study are to assess the safety and maximum tolerated dose of P-BCMA-ALLO1. Secondary end points include overall response rate, duration of response, time to response, progression-free survival, and overall survival.

The study continues to recruit patients and has an estimated primary completion date of December 2027.

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, Inc. September 16, 2024. Accessed September 16, 2024. https://tinyurl.com/3asy95vb

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://tinyurl.com/w7hjyszh

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