Phase 1/1b study of BCMA-targeting bispecific T-cell engager pavurutamab in relapsed/refractory multiple myeloma

The B-cell maturation antigen (BCMA)-targeting bispecific T-cell engager (BiTE®) pavurutamab (AMG 701) directs the cytotoxic T-cell response toward multiple myeloma (MM) cells. This phase 1/1b, open-label, dose-exploration and dose-expansion study evaluated the safety, tolerability, and efficacy of pavurutamab monotherapy in patients with triple-class relapsed/refractory MM (RRMM). Pavurutamab (5-18,000 µg) was administered intravenously weekly with step-up dosing in week 1. Overall, 172 patients received at least one dose of pavurutamab; 73 received the recommended phase 2 dose (RP2D; 18,000 µg), with two different step-up dosing regimens in phase 1b. Twelve patients had dose-limiting toxicities, which included cytokine release syndrome (CRS) and increased transaminases. None occurred at the RP2D. The most frequently reported treatment-emergent adverse events included CRS (74.4%), anemia (61.0%), neutropenia (47.1%), and hypophosphatemia (45.3%). Grade 3 or higher infections were noted in 60 patients (34.9%). The overall response rate was 46.5% among all patients and 65.8% (≥very good partial response VGPR, 60.3%) among 73 patients treated at the RP2D. At median follow-up of 17.2 months, median duration of response was 36.6 months (95% confidence interval CI: 22.3-not estimable). Median progression-free survival for all patients was 5.5 months (95% CI: 2.8-10.1) and 16.8 months (95% CI: 5.0-not estimable) with the RP2D. Pavurutamab exposure generally increased in a dose-proportional manner, with high soluble BCMA levels correlating with lower exposure level. The acceptable safety profile, pharmacokinetics, and preliminary efficacy of pavurutamab supports anti-BCMA T-cell engager therapy in heavily pretreated patients with RRMM. The trial was registered at www.ClinicalTrials.gov as # NCT03287908.