A Phase 1 Study of P-BCMA-ALLO1, a Non-Viral, Allogeneic BCMA Directed CAR-T in Relapsed/Refractory Multiple Myeloma (RRMM): Results from Optimized Lymphodepletion Cohort

Abstract

Introduction: P-BCMA-ALLO1 is an allogeneic (allo) BCMA targeting CAR-T for the treatment of relapsed refractory multiple myeloma (RRMM) manufactured from healthy donor T-cells via non-viral transposon-based integration to produce a high purity T stem cell memory (TSCM)-rich product. The Cas CLOVER™ gene editing system is used to ablate the TCR beta chain and partially knock out the beta-2 microglobulin gene to prevent graft vs host disease (GVHD) and attenuate host vs graft respectively. Objectives: This Phase 1, open-label, dose escalation study in adults with RRMM (NCT04960579) evaluated safety, with a secondary objective of evaluating anti-myeloma effect. Methods: Patients (pts) must have received ≥ 3 prior lines of therapy including a PI, an IMiD and a CD38 mAb or be triple refractory. Prior BCMA targeted therapy is permitted. Several lymphodepletion (LD) regimens were investigated to enable optimal CAR-T expansion. Here, we present data on pts treated in Arm C, with approximately 2 × 106 P-BCMA-ALLO1 cells/kg, after completing the arm C 3-day LD regimen (cyclophosphamide 750 mg/m2/day and fludarabine 30 mg/m2/day), which has been selected for phase 1b expansion. Results: At the time of data cutoff, 21 unique pts and 2 retreated patients with 4+ weeks of follow up had received P-BCMA-ALLO1 in arm C. None required bridging therapy and the median time from enrollment to start of study treatment was 1 day. The median pt age was 61 (39-76) years, 52% were female and 38% were minorities. The median time since diagnosis was 5.1 (1.0-15.1) years. Pts had received a median of 6 (2-14) prior lines of therapy. 61% (including 1 retreatment pt) had received prior BCMA-targeted therapy, 30% (including 1 retreatment pt) had previously received both a BCMA-targeted CAR-T and a TCE. Thirteen (62%) pts had high-risk cytogenetics. P-BCMA-ALLO1 was well tolerated with no DLTs, HLH, GvHD, or parkinsonism. The most common treatment-emergent adverse events (TEAEs) were leukopenia (83%), neutropenia (78%), anemia (61%), thrombocytopenia (61%), and CRS (39%); no pt had ≥ G3 CRS and the 3 (13%) pts who experienced ICANS were all G1. The most common ≥ G3 TEAEs were cytopenias, with most being considered unrelated to P-BCMA-ALLO1. The ORR in the ITT population was 91%, including 5 CR/sCR, 6 VGPRs, and 10 PRs. The ORR was 100% in BCMA naïve pts and 86% in pts who previously received prior BCMA-targeted therapy. The ORR was 86% in the subset of 7 pts who received both prior BCMA-targeted therapy, as well as talquetamab. Conclusions: P-BCMA-ALLO1 is a non-viral, TSCM-rich, allogeneic BCMA-targeting CAR-T rapidly delivered to all eligible pts without the need for bridging therapy. P-BCMA-ALLO1 demonstrates a promising ORR and favorable safety profile, regardless of prior exposure to BCMA-targeted therapy. The P-BCMA-ALLO1-001 (NCT04960579) clinical trial is actively enrolling pts. Updated data will be presented at the conference.