CANCER-AM CANCER SOC

BackgroundBelantamab mafodotin (belamaf) has shown promising antimyeloma activity in relapsed or refractory multiple myeloma (RRMM) as a single agent. It was hypothesized that its multimodal activity may be enhanced by programmed cell death protein 1 pathway inhibition and activation of T cell-mediated antitumor responses. This study investigated the efficacy and safety of belamaf with pembrolizumab in patients with RRMM.MethodsDREAMM-4 (NCT03848845) was an open-label, single-arm, phase 1/2 study divided into dose-escalation (part 1) and dose-expansion (part 2) phases. Patients were >= 18 years old with >= 3 prior lines of therapy including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 agent. Patients received belamaf (2.5 or 3.4 mg/kg, part 1; 2.5 mg/kg, part 2) and 200 mg pembrolizumab for <= 35 cycles.ResultsOf 41 enrolled patients, 34 (n = 6 part 1, n = 28 part 2) who received 2.5 mg/kg belamaf plus pembrolizumab were included in this final analysis. Sixteen patients (47%) achieved an overall response. Minimal residual disease negativity was achieved in three of 10 patients who had very good partial response or better. Five of eight patients who had prior anti-B-cell maturation antigen therapy achieved partial response or better, including two who had B-cell maturation antigen-refractory disease. Common grade >= 3 adverse events were keratopathy (38%) and thrombocytopenia (29%). Despite belamaf-related ocular events, quality-of-life measures remained stable over time. No new safety signals were observed.ConclusionsThe results of DREAMM-4 demonstrated clinical activity and a favorable safety profile of belamaf plus pembrolizumab in patients with RRMM. This trial is registered at as . The phase 1/2 DREAMM-4 study evaluated the combination of a B-cell maturation antigen-directed antibody-drug conjugate, belantamab mafodotin (belamaf), plus pembrolizumab in patients with heavily pretreated, triple class-exposed relapsed/refractory multiple myeloma. Of the 34 patients (n = 6 part 1, n = 28 part 2) who received 2.5 mg/kg belamaf plus pembrolizumab included in this final analysis, 16 (47%) had an overall response, with 29% having a very good partial response or better. The median progression-free survival was 3.4 months (95% CI, 1.4-5.6). The addition of pembrolizumab to belamaf did not lead to new or unexpected safety signals; however, there was only a modest difference in clinical activity observed beyond that achieved with single-agent belamaf and further investigation of the combination is not planned at this time. image