BCMA-targeting BiTE molecule AMG 420 in relapsed or refractory multiple myeloma: a phase 1b open-label expansion study.

AMG 420 is a first-in-class bispecific T-cell engager (BiTE®) molecule directing a cytotoxic T-cell response toward multiple myeloma cells. This phase 1b, open-label, dose-expansion study (NCT03836053) evaluated the safety, tolerability, and efficacy of AMG 420 monotherapy in patients with relapsed/refractory multiple myeloma. Twenty-three patients received continuous intravenous infusion of AMG 420 (200-600 µg/day) in a 6-week cycle. Two dose-limiting toxicities (grade 3 staphylococcal sepsis and recurrent grade 2 cytokine release syndrome [CRS]) were reported. Commonly reported treatment-related adverse events included CRS, headache, and pyrexia. Overall response rate was 34.8%; median progression-free survival was 2.83 months; and minimal residual disease-negative complete responses were reported in 8.7% of patients. Overall, the safety profile and efficacy from AMG 420 established the proof-of-concept of T-cell engager therapy as a promising therapeutic class in multiple myeloma and BCMA as an effective target for T-cell engager therapy.