Safety and clinical activity of belantamab mafodotin with lenalidomide plus dexamethasone in patients with relapsed/refractory multiple myeloma (RRMM): DREAMM-6 arm-A interim analysis.

HANG QUACH University of Melbourne, St. Vincent’s Hospital Melbourne, Melbourne, VIC, Australia info_outline HANG QUACH, Mercedes Gironella, Cindy Lee, Rakesh Popat, Paul Cannell, Ravi Kasinathan, Bikramjit Chopra, Rachel Rogers, Geraldine Ferron-Brady, Seema Shafi-Harji, Nashita Patel, Joanna Opalinska, Ira V. Gupta, Bradley Augustson

Authors HANG QUACH University of Melbourne, St. Vincent’s Hospital Melbourne, Melbourne, VIC, Australia info_outline HANG QUACH, Mercedes Gironella, Cindy Lee, Rakesh Popat, Paul Cannell, Ravi Kasinathan, Bikramjit Chopra, Rachel Rogers, Geraldine Ferron-Brady, Seema Shafi-Harji, Nashita Patel, Joanna Opalinska, Ira V. Gupta, Bradley Augustson Organizations University of Melbourne, St. Vincent’s Hospital Melbourne, Melbourne, VIC, Australia, Department of Hematology, University Hospital Vall d'Hebron, Barcelona, Spain, Royal Adelaide Hospital, Adelaide, SA, Australia, NIHR UCLH Clinical Research Facility, University College London Hospitals, NHS Foundation Trust, London, United Kingdom, Department of Medicine, Royal Perth Hospital, Perth, Western Australia, Australia, GlaxoSmithKline, Upper Providence, PA, GlaxoSmithKline, London, United Kingdom, GlaxoSmithKline, Stevenage, United Kingdom, Department of Haematology, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Background: Belantamab mafodotin (belamaf; BLENREP) is a B-cell maturation antigen-targeting antibody–drug conjugate approved for patients (pts) with RRMM as monotherapy at 2.5 mg/kg Q3W. Preclinical data demonstrate synergy between belamaf and lenalidomide (Len), suggesting added benefit when combined with standard of care such as Len + dexamethasone (Dex). DREAMM-6 (NCT03544281) Arm A is evaluating belamaf in combination with LenDex in pts with RRMM. Methods: This ongoing, two-part, two-arm, open-label study included pts with RMMM previously treated with ≥1 line of therapy (LOT). Pts received 4 belamaf doses/schedules (1.9 mg/kg Q8W or Q4W; 2.5 mg/kg Q4W or Q4W SPLIT dose [50% on Days (D)1, 8] IV) in combination with Len (20 mg PO D1–21) and Dex (20 mg PO/IV D1, 8, 15, 22). Primary objectives were safety (including treatment-related [TR]AEs related to the combination belamaf and LenDex), tolerability, and efficacy (including overall response rate [ORR] defined as ≥partial response). Results: As of this interim analysis (data cut: July 23, 2021), 45 pts received ≥1 dose (12 at 1.9 mg/kg Q8W; 4 at 1.9 mg/kg Q4W; 16 at 2.5 mg/kg Q4W; 13 at 2.5 mg/kg Q4W SPLIT). Across cohorts, the median age was 68 y (range: 36–80). Thirteen pts (29%) had high-risk cytogenetics and 6 (13%) had extramedullary disease. Median prior LOT was 3 (range: 1–11) and 26 (58%) had prior Len treatment. The median duration of follow-up and ORR ranged across cohorts (Table). The median duration of response was only reached in the 1.9 mg/kg Q4W cohort (11.1 mo [95% CI: 3.7–not reached [NR]). At the time of data cut, median progression-free survival was not reached in the 1.9 mg/kg Q8W or 2.5 mg/kg Q4W cohorts. Gr ≥3 TRAEs occurred in 42–85%. Gr ≥3 keratopathy occurred in 0 pts in 1.9 mg/kg Q8W, 1 pt (25%) in 1.9 mg/kg Q4W, 8 pts (50%) in 2.5 mg/kg Q4W, and 6 pts (46%) in 2.5 mg/kg Q4W SPLIT cohorts. Conclusions: Belamaf + LenDex had a tolerable safety profile, with no new safety signals identified in pts with RRMM. AEs, including keratopathy, were common but manageable with dose modifications. Encouraging clinical activity is observed with this combination in pts with RRMM. Follow-up/correlative studies are ongoing. Funding: GSK (Study 207497); drug linker technology licensed from Seagen Inc.; mAb produced using POTELLIGENT Technology licensed from BioWa. Clinical trial information: NCT03544281. Follow-up, ORR, and safety. n, (%), unless specified Belamaf 1.9 mg/kg Q8W + LenDex n=12 Belamaf 1.9 mg/kg Q4W + LenDex n=4 Belamaf 2.5 mg/kg Q4W + LenDex n=16 Belamaf 2.5 mg/kg Q4W SPLIT + LenDex n=13 Duration of follow-up, median, mo 3.4 17.4 16.2 12.0 ORR 5 (42) 3 (75) 10 (63) 9 (69) ≥Very good partial response 2 (17) 2 (50) 8 (50) 5 (38) Gr ≥3 TRAEs 5 (42) 2 (50) 13 (81) 11 (85) AEs leading to dose interruption/delay 11 (92) 3 (75) 13 (81) 12 (92) Serious TRAEs 2 (17) 0 3 * (19) 3 (23) *Includes 1 fatal serious TRAE (febrile neutropenia).