Dreamm-4: evaluating safety and clinical activity of belantamab mafodotin (belamaf) in combination with pembrolizumab in patients with relapsed/refractory multiple myeloma (rrmm)

Abstract

Introduction: Single-agent belamaf (GSK2857916; BLENREP) has shown deep and durable responses and a manageable safety profile in patients with heavily pretreated RRMM (DREAMM-2, NCT03525678, Lancet Oncol 2020). Immune surveillance in patients with RRMM is often blunted through the PD-1/PDL-1 axis; PDL-1 being highly expressed on MM cells. PD-1 inhibitor pembrolizumab, may augment immune responses to belamaf-induced immunogenic cell death. DREAMM-4 (NCT03848845) is an ongoing Phase I/II, two-part study assessing safety and efficacy of belamaf plus pembrolizumab in patients with RRMM. Methods: Patients had ≥3 prior lines of therapy, including anti-CD38 treatment. Planned enrollment for both parts is up to 40 patients. Part 1 (dose escalation) evaluates 2.5 or 3.4 mg/kg belamaf plus 200 mg pembrolizumab in up to 12 patients to establish the recommended Phase II dose (RP2D) of this combination. Both drugs are given IV Q3W for up to 35 cycles. Part 1 interim analyses (IA) are presented. Part 2 (dose expansion) will confirm safety and assess clinical activity at the RP2D; overall response rate (ORR; ≥partial response) is the primary endpoint. Results: As of 4 Feb 2020, 6 and 7 patients were enrolled at the 2.5 and 3.4 mg/kg doses, respectively (1 patient replaced as per protocol). In the 2.5 and 3.4 mg/kg groups, median (range) prior lines of therapy were 7.5 (3–13) and 5.0 (3–8), and 3/6 (50%) and 1/7 (14%) patients had high-risk cytogenetics. No dose-limiting toxicities were reported in either group. All patients in both groups experienced adverse events (AEs) and treatment-related AEs. The most frequent AEs of any grade and Grade 3/4 are reported in the Table. Serious AEs (SAEs) were reported in 50% (3/6) of patients in the 2.5 mg/kg group (n=1 had a treatment-related SAE) and 43% (3/7) of patients in the 3.4 mg/kg group (n=3 had a treatment-related SAE). No Grade 5 AEs occurred. Keratopathy (microcyst-like epithelial changes [MECs], with/without symptoms) was the primary reason for dose delays (2.5 mg/kg group: 67%; 3.4 mg/kg group: 14%) and dose reductions (2.5 mg/kg group: 17%; 3.4 mg/kg group: 0%). The ORR was 67% and 14% in the 2.5 and 3.4 mg/kg groups, respectively (Table). PK data and free soluble BCMA levels were consistent with previous studies. Conclusion: Belamaf plus pembrolizumab demonstrated a manageable safety profile and clinical activity in patients with RRMM. Keratopathy (MECs) was the most frequent AE, consistent with belamaf studies, and managed with dose modifications. Part 1 IA supports continuation with Part 2 of this study. Funding: GSK (205207) in collaboration with Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Drug linker technology licensed from Seattle Genetics; monoclonal antibody produced using POTELLIGENT technology licensed from BioWa. Encore Statement: This abstract was accepted and previously presented at EHA 2020 (Nooka et al EP955). Resubmitted with permission.