Belantamab treatment of multiple myeloma: Results from part 1 of the first-in-human phase 1/2 DREAMM-20 trial.

7550 Background: Belantamab mafodotin (belamaf) is a B-cell maturation antigen (BCMA)–targeted monoclonal antibody (mAb) conjugated with a monomethyl auristatin-F (MMAF) payload. In DREAMM-7 and DREAMM-8 phase 3 trials in relapsed/refractory multiple myeloma (RRMM), belamaf combinations significantly improved progression-free survival vs standard care, and DREAMM-7 showed significant overall survival benefit. Belantamab (GSK2857914) is the naked BCMA mAb without MMAF; therefore MMAF-related toxicities are not expected. DREAMM-20 is a phase 1/2 trial to evaluate safety, tolerability, and clinical activity of belantamab in patients (pts) with MM. We present the planned analysis of part 1 of belantamab dose escalation. Methods: Part 1 of DREAMM-20 (NCT05714839) is a phase 1, open-label, multicenter, dose-escalation study in pts with RRMM with ≥3 prior lines of therapy. Dose escalation was conducted using a modified toxicity probability interval method. The primary endpoint was incidence of adverse events (AEs), including dose-limiting toxicities (DLTs). Secondary endpoints included overall response rate (ORR). Results: Across 3 cohorts, 18 pts enrolled and received belantamab 300, 900 or 2000 mg IV Q2W (n=6 each). Data cutoff (DCO) was Aug 23, 2024. Median age was 76 y (range, 42-86 y), 17 of 18 pts were triple-class exposed, and 2 of 18 pts had prior BCMA-targeted therapy. The overall median duration of exposure was 63.5 days. No DLTs or treatment-related AEs (TRAEs) leading to permanent discontinuation were reported. The most common TRAEs were infusion-related reactions and hematologic AEs (Table). Two pts had grade ≥2 corneal events per the Keratopathy and Visual Acuity (KVA) scale that were considered unrelated to belantamab. The ORR was 28% (5/18 pts; very good partial response, n=2 [900 mg]; partial response, n=3 [1 in 300 mg and 2 in 2000 mg]) with responses across all cohorts. Median duration of exposure in the 5 responders was 253 days; none of the responders had progressed as of DCO. No pts had minimal response and 28% (5/18 pts) had stable disease. Follow-up is ongoing. Conclusions: Belantamab showed an encouraging safety profile with no DLTs, AEs leading to discontinuation, or belantamab-related grade ≥2 corneal events. Durable responses were observed across dose levels in this triple-class–exposed population. Results support the hypothesis that belantamab provides clinical antimyeloma activity with an acceptable safety profile. Clinical trial information: NCT05714839 . n (%) Belantamab 300, 900, or 2000 mg (N=18) Any-grade AEs 17 (94) TRAEs 12 (67) Most common TRAEs (≥2 patients) Infusion-related reactions Neutrophil count decreased Anemia Vision blurred Platelet count decreased 4 (22)4 (22)2 (11)2 (11)2 (11) Grade ≥3 AEs 12 (67) Most common grade ≥3 AEs (≥2 patients) Neutrophil count decreased Anemia 4 (22)3 (17) Serious AEs Treatment related 6 (33)1 (6) Fatal AEs 0