Efficacy of Elranatamab (ELRA) in Combination with Carfilzomib (CFZ) and Dexamethasone (DEX) in the Phase lb MagnetisMM-20 Trial in Relapsed or Refractory Multiple Myeloma (RRMM)
Introduction/Background/Significance: Elranatamab induced deep and durable responses with manageable safety in BCMA-naive patients with RRMM in MagnetisMM-3 (NCT04649359). Combining elranatamab with carfilzomib may enhance immune surveillance of MM cells. Here we present Part 1 results from Phase 1b MagnetisMM-20 (NCT05675449) trial of elranatamab, carfilzomib, and dexamethasone (EKd) in RRMM.
Materials and Methods/Case Presentation/Objective: Eligible patients (≥ 18 years) had BCMA-naive RRMM, 1-3 prior LOTs, ECOG PS ≤1. Prior carfilzomib allowed if ≥PR to most recent carfilzomib-containing therapy and no relapse ≤60 days after discontinuation, with ≥6 month carfilzomib-free interval. Patients received premedication and 12 and 32 mg step-up priming doses of days 1 and 4 of cycle 0, followed by 44mg (DL1) or 76 mg (DL2) on day 8. Patients with ≥6 months of QW dosing and ≥PR lasting ≥2 months switched to Q2W dosing. Carfilzomib and dexamethasone were administered per label. Primary endpoint is DLTs. Secondary endpoints include AEs, laboratory abnormalities, BOR, ORR, complete response rate, TTR, DOR, PFS, and OS.
Results/Description/Main Outcome Measures: Of 12 treated patients, median age was 66.0 years (range, 45.0-80.0), 8 (66.7%) were male, and 3 (25.0%) had high-risk cytogenics. Patients had a median of 2 prior LOTs (range, 1-3), 41.7% triple-class refractory disease; 8 (66.7%) had an SCT. At data cutoff (September 13, 2024), 41.7% patients were ongoing elranatamab and carfilzomib treatment. Median treatment duration was 8.4 months (range, 0.6-20.1).
No DLTs were reported (10 evaluable patients). The most common AEs overall (n=12, any grade [≥50%], grade 3/4 [≥10%]) were infections (91.7%, 16.7%), fatigue (83.3%, 16.7%), CRS (75.0%, 0%), neutropenia (75.0%, 75.0%), thrombocytopenia (75.0%, 41.7%), leukopenia (66.7%, 33.3%), anemia (66.7%, 33.3%), cough (58.3%, 0%), diarrhea (50.0%, 8.3%), CMV infection reactivation (50.0, 8.3%), injection site reaction (50.0%, 0%), lymphopenia (33.3%, 25.0), peripheral edema (33.3%, 16.7%), increased blood alkaline phosphatase (25.0%, 16.7%), and pulmonary embolism (16.7%, 16.7%). No ICANS was reported.
At a median follow-up (reverse KM) of 8.9 months (95% CI, 7.9-13.7), confirmed ORR by investigator was 100%; median TTR was 1.5 months (range, 0.5-3.4). Median DOR was not reached.
Conclusions: EKd has demonstrated clinical efficacy and predictable safety. The study continues enrolling and will explore this combination in a larger patient population.
