A Phase I/II Single Arm Study of Belantamab Mafodotin, Carfilzomib and Dexamethasone in Patients with Relapsed Multiple Myeloma: Planned Interim Analysis of Safety and Efficacy. Amarc 19-02 Belacard Study

Introduction Belantamab Mafodotin (Belamaf, B), a first in class anti-B-cell maturation antigen (BCMA) antibody-drug conjugate, is efficacious in triple-class exposed, relapsed and refractory multiple myeloma (RRMM). Combination therapy with carfilzomib and dexamethasone (Kd) is potentially synergistic through different anti-myeloma mechanisms of action. We report here a planned interim analysis of safety and responses after the first two cycles of combination therapy. Methods BelaCarD is an ongoing, single-arm, multicentre phase I/II study evaluating 8-weekly B dosing schedule in combination with Kd in patients (pts) with RRMM after 1-3 lines of therapy. B (2.5mg/kg) was administered intravenously (IV) on day (D)1 of every second 28D cycle; K 70mg/m2 IV D1 (20mg/m2 on C1D1), D8 and D15 of every cycle and dexamethasone 40mg weekly (20mg/m2 for pts >75 years). Treatment was continued until disease progression. Corneal adverse events (AEs) were graded as per the keratopathy and visual acuity (KVA) scale and all other AEs as per CTCAEv5. Confidence interval coefficients for response rates (RR) were adjusted using an alpha-spending function. The primary objective is progression free survival (PFS). Results As of 13 th July 2023, 65 pts (67% male) of the intended 70 have been enrolled. 55 pts (62% male) received minimum 2 cycles of B-Kd and were included in the protocol-specified interim analysis. The median age was 69.7 years (48-81); 18 pts (33%) had high-risk cytogenetics either at diagnosis or screening. ISS stage I, II, III occurred in 47.3%, 23.6% and 10% respectively. 25.5%, 38.2% and 34.6% pts had 1, 2 and 3 prior lines of therapy respectively including (exposed/refractory) bortezomib (90.9%/42%), K (3.6%/50%), lenalidomide (52.7%/44.8%), pomalidomide (5.5%/33%), anti-CD38 monoclonal Ab (mAb) (30.9%/52.9%), autologous stem cell transplant (ASCT) (41.8%). The median number of cycles received was 9 (2-27). Treatment-related AEs were reported in 93% of pts (Gr3 60%, Gr4 13%); most frequent were (all grade, Gr3, Gr4): blurred vision (40%, 7.3%, 0%), nausea/vomiting (29.1%, 3.6%, 0%), insomnia (23.6%, 10.9%, 0%), thrombocytopenia (23.6%, 10.9%, 5.5%). Ocular AEs occurred in 42 (79.2%) out of 53 evaluable pts including decline in best corrected visual acuity (BCVA) (total 77.2%, Gr1 9.4%, Gr2 33.9%, Gr3 33.9%) and keratopathy (K) (total 75.4%, Gr1 5.6%, Gr2 22.6%, Gr3 47.2%). Median time to reach worst-grade BCVA and K was 106 (25-309) and 76.5 (25-231) days respectively. Median time to return to Gr ≤1 BCVA and K was 61 (28-322) and 94 (30-326) days respectively. Ten pts had B-related SAEs (Gr 1/2 n=2, Gr 3 n=6, Gr 4 n=1, one pt died of sepsis). A second treatment-related death was due to pneumonia. Six pts discontinued therapy due to treatment-related AE including 4 due to B (corneal toxicity n=2, sepsis n=1, proteinuria n=1). Overall RR and ≥ VGPR by end of cycle 2 were 80% (97%CI: 65.3 - 90.5) and 40% (97%CI: 25.5 - 55.9) respectively. At estimated median potential follow-up of 13 months (4-38), the preliminary estimate of PFS at 24m was 56.1%. Conclusion B-Kd with an extended B schedule demonstrates a manageable safety profile. The preliminary efficacy data is encouraging with deep responses observed after only 2 cycles of therapy. Recruitment is close to completion with the main analysis to be conducted once all pts have completed the 12-month assessment. Acknowledgement: pts, their families and participating AMaRC members and sites as well as the support of GSK and funding support from the Victorian Cancer Agency.