P14: DREAMM-9: PHASE I STUDY OF BELANTAMAB MAFODOTIN PLUS STANDARD OF CARE IN PATIENTS WITH TRANSPLANT-INELIGIBLE NEWLY DIAGNOSED MULTIPLE MYELOMA
Authors: S Usmani, A Alonso, H Quach, Y Koh, A Guenther, CK Min, X Leleu, AO Abdallah, A Oriol, B Bessemer, M Garg, I Sandhu, K Weisel, E Ocio San Miguel, M Cavo, X Zhou, M Kaisermann, L Mis, D Williams, A Yeakey, G Ferron-Brady, D Figueroa, B Kremer, I Gupta, W Janowski
Journal: HemaSphere (2022)

Background: The bortezomib, lenalidomide, and dexamethasone (VRd) regimen is a SoC for NDMM. Belamaf, a B-cell maturation antigen (BCMA)–targeting antibody-drug conjugate, demonstrated durable responses in patients with relapsed/refractory multiple myeloma. Preclinical studies of belamaf in combination with bortezomib/lenalidomide suggest enhanced antimyeloma activity. We report preliminary findings of belamaf + VRd for patients with TI NDMM. Materials and Methods: DREAMM-9 (NCT04091126) is an ongoing Phase I, open label, randomized, dose and schedule evaluation trial. Adults with TI NDMM and ECOG status 0–2 are eligible. VRd is administered Q3W until Cycle 8, followed by lenalidomide + dexamethasone (Rd) Q4W. Belamaf + VRd is administered until Cycle 8, and with Rd thereafter. The currently evaluated belamaf dose cohorts are: Cohort 1 (1.9 mg/kg Q3/4W), Cohort 2 (1.4 mg/kg Q6/8W), Cohort 3 (1.9 mg/kg Q6/8W), Cohort 4 (1.0 mg/kg Q3/4W), and Cohort 5 (1.4 mg/kg Q3/4W). Primary endpoint is safety. Secondary endpoints include efficacy, tolerability, and pharmacokinetics (PK). Results: Overall 36 patients were treated across the 5 cohorts. The median (range) age was 74.0 (63–80) years; 56% patients were male, 17 (47%) had stage 2 disease, 3 (8%) had extramedullary disease, 6 (17%) patients had high risk cytogenetic abnormalities; the median number of belamaf cycles ranged from 1–9. No new safety signals were observed. Across Cohorts 1–5, all patients experienced AEs related to study treatment; 1 patient in Cohort 1 died due to COVID-19 infection. The most common AEs leading to dose modification were thrombocytopenia, neutropenia, and corneal events. Patients in Cohort 2 and 3 had the lowest number of Grade ≥3 corneal events (3 and 2 events, respectively). All 12 patients in Cohort 1, all 6 in Cohorts 3 and 5, and 5/6 patients in Cohorts 2 and 4 have responded to the treatment; ≥half of patients in each cohort achieved very good partial response or better. As of data cut-off, 3/12 patients in Cohort 1, 2/6 in Cohort 4, and 1/6 patients each in Cohorts 3 and 5 remained in complete response. Belamaf PK profile was similar to that observed in patients with RRMM taking into consideration baseline patients characteristics. Conclusions: Preliminary data suggest addition of belamaf to VRd did not reveal new safety signals and demonstrates high response rates, albeit with short follow-up. The trial is ongoing to confirm safety and evaluate the efficacy of belamaf + VRd. Funding: GSK (Study 209664); drug linker technology licensed from Seagen Inc; mAb produced using POTELLIGENT Technology licensed from BioWa. Encore statement: Previously presented as Poster 2738 at the American Society of Hematology Annual Meeting, 11–14 December 2021; submitted with permission and on behalf of the original authors.