DREAMM-9: PHASE I STUDY OF BELANTAMAB MAFODOTIN PLUS STANDARD OF CARE IN PATIENTS WITH TRANSPLANT-INELIGIBLE NEWLY DIAGNOSED MULTIPLE MYELOMA

ABSTRACT

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. .