The overall response rate to P-BCMA-ALLO1 was 88% among 32 patients, including 100% in patients who had no prior BCMA-targeted therapy and 75% in patients who had received at least 1 prior anti-BCMA treatment. Among 9 patients who had received prior BCMA-targeted and GPRC5D-targeted therapy (talquetamab [Talvey]), the ORR was 78%.

Safety results showed that 42% of patients experienced grade 1/2 cytokine release syndrome (CRS), with a median time to onset of 8 days (range, 2-12), and median time to CRS resolution of 11 days (range, 4-39). There were cases of grade 3 or higher CRS reported. Grade 1/2 immune effector cell–associated neurotoxicity syndrome (ICANS) occurred in 14% of patients, with a median time to onset of 4 days (range, 3-9), and a median time to resolution of 7 days (range, 3-10). There were no grade 3 or higher cases of ICANS reported.

Half of patients had grade 1/2 infection and 5 patients had grade 3 or higher infection. There was no graft-versus-host disease observed at any study dose. Five patients experienced neurotoxicity, which was all grade 1, and there were no cases of Parkinsonism or neuropathies.

The most common grade 3 or higher treatment-related adverse events included neutropenia (50%), leukopenia (44%), thrombocytopenia (36%), and anemia (39%).

There was 1 patient death on day 6 of the trial due to complications from infection, which was determined to be related to lymphodepletion not to P-BCMA-ALLO1.

Results: At the time of data cutoff, 21 pts with 4+ weeks of follow up had been treated in this LD arm. None required bridging therapy and the median time from enrollment to start of study treatment was just 1 day (range: 0-9 days), highlighting the rapid availability of P-BCMA-ALLO1, being an off-the-shelf CAR-T. 100% of the intent to treat (ITT) population received P-BCMA-ALLO1.

The median pt age was 61 (39-76) years, 53% were female and 42% were minorities. The median time since multiple myeloma diagnosis was 7.0 (1.0-15.1) years. Pts were heavily pretreated, with a median of six (2-14) prior lines of therapy. 62% had undergone prior BCMA-targeted CAR-T and/or T cell engager (TCE) therapy, 29% had previously received both a BCMA-targeted CAR-T and/or TCE and Talquetamab. Thirteen (62%) pts had high-risk FISH anomalies.

P-BCMA-ALLO1 was well tolerated with no DLTs or GvHD. The most common treatment-emergent adverse events (TEAEs) were neutropenia (71%), leukopenia (67%), anemia (52%), thrombocytopenia (48%), and CRS (43%). The most common ≥ G3 TEAEs were neutropenia (67%), leukopenia (67%) anemia (43%), and thrombocytopenia (33%). Most AEs were considered unrelated to P-BCMA-ALLO1. Of nine (43%) pts with CRS, seven (33%) had G1 CRS and two (10%) had G2 CRS; no pt had > G3 CRS. Three (14%) pts experienced ICANS, all were G1.

P-BCMA-ALLO1 demonstrated an encouraging overall response rate (ORR) in all relevant pt subsets. The ORR in the ITT population was 90%, including 6 CR/sCR, 5 VGPRs, and 8 PRs. The ORR was 100% in BCMA naïve pts and 85% in pts who previously received BCMA-targeted therapy. The ORR was 83% in the subset of 6 pts who received both prior BCMA-targeted agents, and Talquetamab.

To assess whether BCMA expression impacted clinical activity, baseline BCMA levels (BCMA MESF on CD138+CD38+ bone marrow cells) were evaluated for 12 pts, showing a median MESF of 4,685 (2,125-23,537). The median BCMA MESF for the 6 BCMA-naïve pts tested was 8,859 (4,098-23,537), while the median for the 6 pts with prior BCMA therapy was 2744 (2125-5912). P-BCMA-ALLO1 cellular kinetics (CK) were assessed (n=15) using ddPCR demonstrating a median Cmax of 49,430 (66-501,678) cp/µg of the CAR transcript at a median Tmax of 10 (7-21) days. The median CK for the BCMA naïve pts (n=7) was 72.077 (10,904 – 501,678) cp/µg, while the median CK for BCMA exposed pts (n=8) was 27,878 (66 – 310,209) cp/µg. There was no statistical difference between these groups.

Conclusions: P-BCMA-ALLO1 is a non-viral, TSCM-rich, allogeneic BCMA-targeting CAR-T quickly delivered to all eligible pts without the need for bridging therapy. P-BCMA-ALLO1 demonstrates a promising ORR and favorable safety profile when administered with optimized LD. It is highly active, regardless of prior exposure to BCMA-targeted autologous CAR-T or TCE therapy. As an allogeneic therapy, it also offers significant practical advantages over autologous CAR-T, which require apheresis, prolonged, often uncertain manufacturing, and bridging therapy; and TCE, which require chronic administration. The P-BCMA-ALLO1-001 clinical trial is actively enrolling pts. Updated safety and efficacy data will be presented at ASH 2024.

New Interim Clinical Data from Phase 1 P-BCMA-ALLO1 Trial 

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 September 6, 2024, 72 unique patients were enrolled 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 BCMA-and/or 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, demonstrating Poseida's commitment to underserved patient populations.

In the ITT population, 100% of patients enrolled as of the data cutoff 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 – the cohorts 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.