Preliminary results of the phase 1 MagnetisMM-1 study indicated that the BCMA-targeted CD3-engaging bispecific molecule elranatamab had a manageable safety profile and induced deep and durable clinical responses as a single agent in heavily treated patients with RRMM.
The 2-part, multicohort, phase 1 MagnetisMM-1 study (NCT03269136) evaluated the safety and antitumor activity of the B-cell maturation antigen (BCMA)-targeted CD3-engaging bispecific molecule elranatamab (PF-06863135) in patients with relapsed/refractory multiple myeloma (RRMM). Results from the dose escalation (part 1), monotherapy with priming (part 1.1), lenalidomide combination (part 1C), pomalidomide combination (part 1D), and monotherapy expansion with priming (part 2A) were presented at the 2021 ASH Annual Meeting and summarized here.
In the part 1 dose-escalation phase of the study, patients received subcutaneous elranatamab at 80, 130, 215, 360, 600, and 1000 μg/kg weekly using a modified toxicity probability interval method. In parts 1.1 and 2A of the study that evaluated monotherapy at the recommended phase 2 dose (RP2D), a single priming dose of elranatamab (600 μg/kg or equivalent fixed dose of 44 mg) was followed 1 week later by the full dose (1000 μg/kg or equivalent fixed dose of 76 mg) weekly or every 2 weeks thereafter. For lenalidomide (part 1C) or pomalidomide combination therapy (part 1D), a single priming dose (32 mg) of elranatamab was followed 1 week later by the full dose (44 mg), and weekly thereafter in combination with either lenalidomide (25 mg) or pomalidomide (4 mg) on days 1 to 21 of a 28-day cycle. Dose-limiting toxicity was monitored to the end of the first cycle. Minimal residual disease was assessed by next-generation sequencing at a threshold of 1 × 10–5. The data cutoff date was July 26, 2021.
A total of 65 patients received elranatamab, either as a single agent at efficacious dose levels ≥215 μg/kg (N = 55) or in combination with either lenalidomide (N = 4) or pomalidomide (N = 4). The median age of the patient population was 64 years and patients were heavily pretreated, with a median of 6 previous regimens; 90.9% had triple-class relapsed/refractory disease, 45% had previous high-dose chemotherapy with stem-cell transplantation, and 21.8% had previous BCMA-targeted therapy. RP2D was established at 1000 μg/kg.
The most common all-causality treatment-emergent adverse events (TEAEs) included cytokine release syndrome (CRS; 87.3%), neutropenia (70.9%), anemia (65.5%), injection-site reaction (56.4%), lymphopenia (50.9%), and thrombocytopenia (49.1%). Grade 3/4 TEAEs were mostly hematologic. CRS events were only grade 1 or 2. Median duration of CRS decreased at the RP2D of 1000 μg/kg (from 4 days to 3 days) with priming. One dose-limiting toxicity was reported, a grade 4 thrombocytopenia (part 1.1) and grade 4 neutropenia (pomalidomide cohort).
In the dose-escalation cohort (median follow-up of 12.5 months), 14 of 20 (70%) patients achieved a confirmed overall response rate, with 7 complete responses (CR)/stringent CRs, 6 very good partial responses, and 1 partial response. At the RP2D (N = 6), the confirmed overall response rate was 83%. Median time to response was 22 days; median duration of response among responders (N = 14) had not yet been reached. Of evaluable patients (N = 4), minimal residual disease negativity (1 × 10–5) was achieved by all 4 with baseline dominant sequence and on-treatment sample at CR/stringent CR. Responses were achieved regardless of previous BCMA-targeted therapy; 3 of 4 (75%) patients achieved responses, 1 stringent CR and 2 very good partial responses. Data of lenalidomide and pomalidomide combination cohorts were pending at the time of this abstract release.
Based on these phase 1 study results, it was concluded that elranatamab had a manageable safety profile and induced deep and durable clinical responses as a single agent, regardless of previous BCMA-targeted therapy in heavily treated patients with RRMM.
Source: Sebag M, Raje NS, Bahlis NJ, et al. Elranatamab (PF-06863135), a B-cell maturation antigen (BCMA) targeted CD3-engaging bispecific molecule, for patients with relapsed or refractory multiple myeloma: results from MagnetisMM-1. Blood. 2021;138(suppl 1):895.