Open-label, single-arm phase Ib/II study of immune combination therapy with elotuzumab and belantamab mafodotin in patients with relapsed refractory multiple myeloma.
Authors: Sabrina Browning, Fangyong Li, Terri L. Parker, Noffar Bar, Tara Anderson, Erica Stevens, Jennifer VanOudenhove, Martin Matthews, Elan Gorshein, Ashita D. Talsania, Kert D. Sabbath, Stuart Seropian, Stephanie Halene, Natalia Neparidze
Journal: Journal of Clinical Oncology (2024)

7559 Background: The B cell maturation antigen (BCMA)-targeted antibody drug conjugate belantamab mafodotin enhances cell-mediated antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis. Elotuzumab, a signaling lymphocytic activation molecule family member 7 (SLAMF7) checkpoint inhibitor, activates NK cells and induces antibody-dependent cellular cytotoxicity. Bela-Elo (NCT05002816) is an ongoing phase Ib/II trial evaluating the safety, tolerability and preliminary efficacy of the unique combination of these two agents in patients with relapsed/refractory myeloma (RRMM). We report data from phase I part of this trial. Methods: This single-arm phase Ib/II study is enrolling patients with triple-class refractory RRMM. Patients with progression after prior BCMA-targeted therapy are eligible. Elotuzumab is administered via intravenous (IV) infusion at an established dose of 10 mg/kg on days 1, 8, 15, 22 every 28 days for cycles 1 and 2; followed by 20mg/kg on day 1 of each 28-day cycle. Belantamab mafodotin is administered via IV infusion with the starting dose of 1.9 mg/kg IV at every 4-week interval, with subsequent dose-reduction based on toxicity. Descriptive statistics were used to summarize patient demographics and safety and efficacy outcomes. Results: As of data cut-off (January 20, 2024) 12 subjects have been enrolled; and 10 subjects received treatment on study. Median age of patients was 66.5 years (range 59-79). The patient population was heavily pretreated with 5 prior median lines of therapy (range 2-8); 40% (4/10) of patients were refractory to prior BCMA-targeted therapy (2 post-BCMA bispecific antibody, 2 post-BCMA chimeric antigen receptor T-cell therapy [CART]). Phase I part of the study has completed. Median duration of treatment was 4 months (range 2-19). No dose-limiting toxicities were observed. Four severe adverse events were observed possibly related to the study treatment in 3 patients, including grade 3 pulmonary infection (n=1) and lymphopenia (n=3). Ocular keratopathy developed in 40% of patients, all were grades 1-2 and resolved after discontinuation or dose-reduction of belantamab. Preliminary activity is noted with partial responses (PR) in 4/10 (40%) and stable disease (SD) in additional 3/10 (30%) of patients. Among the four patients who were refractory to prior BCMA therapy, 2 (50%) achieved PR, with duration of response (DOR) of 19 months and 9 months, respectively. Conclusions: This novel combination immune therapy with belantamab mafodotin and elotuzumab appears to have an encouraging safety profile and a promising preliminary efficacy in patients with heavily pretreated RRMM, including in those with prior failure of BCMA-targeted therapy. Clinical trial information: NCT05002816 .