Poseida Therapeutics Garners FDA RMAT Designation for Allogeneic CAR-T P-BCMA-ALLO1 in R/R Multiple Myeloma
The product is currently being evaluated in a phase 1/1b clinical trial.
Poseida Therapeutics’ P-BCMA-ALLO1, an allogeneic chimeric antigen receptor T-cell (CAR-T) therapy, has received regenerative medicine advanced therapy (RMAT) designation from the FDA for the treatment of adults with multiple myeloma (MM) whose disease is relapsed/refractory (r/r) following at least 3 previous lines of treatment that included a proteasome inhibitor, an immunomodulatory agent, and an antiCD38 antibody.1
P-BCMA-ALLO1 is comprised of T-cells, rich in stem cell memory T-cells (TSCM), that are genetically modified to target B-cell maturation antigen (BCMA) with a VH-based binder. The product is currently being evaluated in a phase 1/1b clinical trial (NCT04960579). The open-label, dose-escalation study is open to patients aged 18 years and older who have a confirmed diagnosis of active r/r MM and have previously received treatment with a proteasome inhibitor, an immunomodulatory agent, and antiCD38 therapy, or have disease that is otherwise triple-refractory.1,2 P-BCMA-ALLO1 is the subject of a strategic collaboration agreement between Poseida and Roche that was established in 2022.3 The CAR-T has previously received orphan drug designation from the FDA for MM.1
"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 r/r MM," Kristin Yarema, PhD, the president and chief executive officer of Poseida Therapeutics, said in a statement.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 therapy, including the recently initiated phase 1b portion of the trial."
Early data from the clinical trial was previously presented at the the 2023 American Society of Hematology (ASH) Annual Meeting & Exposition, held December 9-12, in San Diego, California.3 The efficacy data reported came from 11 of 33 patients who were evaluable with at least 4 weeks of follow-up. These 11 patients were part of cohorts that received a preconditioning regimen that included a higher dose of cyclophosphamide: either 500 mg/m2 ('P1 arm'; n = 5) or 1,000 mg/m2 ('P2 arm'; n = 6). For these 11 patients, the overall objective response rate (ORR) was 82% (9/11), with an ORR of 80% in P1 (4/5) and an ORR of 83% in P2 (5/6). In terms of safety, P-BCMA-ALLO1 was characterized as “very well-tolerated". Among all evaluable patients, rates of cytokine release syndrome (CRS) and neurotoxicity were deemed low, with no cases graded higher than grade 2. There were no cases of graft versus host disease reported. Poseida plans to presented updated results from the trial at the 21st International Myeloma Society Annual Meeting, held in Rio de Janeiro from September 25 to 28, 2024.1
"Today, far too many patients are unable to benefit from autologous CAR-T therapy due to its limited supply, lengthy timelines, complex logistics, and cost," Yarema said in a December 2023 statement.2 "We have long believed that readily produced, off-the-shelf allogeneic, TSCM-rich CAR-T products have the potential to offer a compelling efficacy and safety profile while also supporting patient access. TSCM-rich CAR-T products can be difficult to produce with older virus-based technology, but we are able to create a portfolio of such products using Poseida's unique, nonviral set of technologies. We see these early P-BCMA-ALLO1 results in MM, in which all enrolled patients received CAR-T therapy and most patients receiving adequate lymphodepletion achieved a stringent complete response or very good partial response, as validating our vision and eagerly await additional data yet to come from this study. This is also the first known publicly presented data set that provides clear clinical evidence supporting the hypothesis that TSCM cells are the ideal cell type for allogeneic CAR-T, extending our previous findings with autologous TSCM cells to the allogeneic setting.”
