New Interim Clinical Data from Phase 1 P-BCMA-ALLO1 Trial
On September 27, 2024, Poseida Therapeutics, Inc. (the “Company”) announced new interim clinical data from its ongoing Phase 1 trial of P-BCMA-ALLO1 in patients with relapsed/refractory multiple myeloma (“RRMM”).
P-BCMA-ALLO1 is an investigational non-viral, stem cell memory T cell (“TSCM”)-rich allogeneic CAR-T cell therapy in Phase 1/1b clinical development for the treatment of patients with RRMM. The Company is developing this investigational off-the-shelf allogeneic CAR-T cell therapy with F. Hoffmann-La Roche Ltd and Hoffmann-La Roche Inc. (collectively, “Roche”) as part of a broader collaboration focused on addressing blood cancers with the Company’s TSCM-rich CAR-T platform.
Data, based on an efficacy cutoff date of September 6, 2024 and a safety cutoff date of July 31, 2024, demonstrated a 91% overall response rate (“ORR”) and compelling safety results in the 23 heavily pretreated patients in Arm C, an optimized lymphodepletion arm. The new clinical data were presented on September 27, 2024 in an oral session at the 21st International Myeloma Society Annual Meeting (“IMS”) in Rio de Janeiro.
The ongoing open-label, multicenter Phase 1/1b dose-escalation and expansion trial in patients with RRMM is assessing the safety and maximum tolerated dose of P-BCMA-ALLO1 (primary objective) and its anti-myeloma activity (secondary objective). As of July 31, 2024, 72 unique patients were enrolled and had at least 4 weeks of follow-up as an intent-to-treat (“ITT”) population and were treated across four study arms (S, A, B and C) that included different P-BCMA-ALLO1 doses and lymphodepletion regimen combinations. Study participants were required to have received three or more prior lines of therapy, including a prior proteasome inhibitor, immunomodulatory drug and anti-CD38 monoclonal antibody. The trial enrolled a heavily pretreated patient population with 43% of patients having received prior B-cell maturation antigen (“BCMA”)- and/or G protein-coupled receptor class C group 5 member D (“GPRC5D”)-targeting therapy. Most prior BCMA therapies included autologous CAR-T and/or T-cell engagers (“TCE”). Additionally, 33% of study participants were racial minorities.
In the ITT population, 100% of patients enrolled were infused with P-BCMA-ALLO1. No patients required anti-myeloma bridging therapy or prophylaxis with steroids or tocilizumab, and there was no invasive apheresis or manufacturing wait time. The median time from enrollment to the start of study treatment was one day.
The ORR across all four study arms was 54%; 11% of patients achieved a complete response (“CR”) or a stringent complete response (“sCR”), and 33% achieved a very good partial response or higher (“VGPR+”). The median duration of response (“DoR”) was 232 days for study Arms A and B, including patients with six or more months of follow-up at the time of data cut-off. Expansion and persistence of the CAR-T cells in patients after infusion has been dependent upon the conditioning dose of cyclophosphamide. P-BCMA-ALLO1 levels measured in the peripheral blood and were much higher in patients in Arm C (cyclophosphamide 750 mg/m2/day) and Arm B (cyclophosphamide 1000 mg/m2/day) than in patients in Arm S (cyclophosphamide 300 mg/m2/day), and Arm A (cyclophosphamide 500 mg/m2/day). Arm C was identified as the optimized lymphodepletion arm based on cellular kinetics, safety and efficacy.
Results from 23 study participants in Arm C were highlighted in the oral session at IMS. Patients received cyclophosphamide 750 mg/m2/day and fludarabine 30 mg/m2/day and approximately 2x106 cells/kg P-BCMA-ALLO1. Some patients were treated in an outpatient setting. Arm C patient details include:
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Nearly half (48%) were age 65 or older |
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All were heavily pretreated, with a median of six prior lines of anti-myeloma therapy and a maximum of 14 |
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62% of patients had received prior BCMA-targeting therapy |
