7512 Background: The MAIA trial established daratumumab with lenalidomide, dexamethasone (DRd) as standard therapy for transplant-ineligible (TI) NDMM. Belantamab mafodotin (belamaf) showed high efficacy in relapsed/refractory disease. Quadruplet regimens improved clinical outcomes, providing a strong rationale to evaluate belamaf in combination with DRd in TI NDMM. Methods: BelaDRd is a phase 1/2, open-label study (EUCT-2024-515634-32) evaluated this combination in TI-NDMM. Part 1 (dose-finding phase) assessed the safety and tolerability of two belamaf doses (1.9/1.4 mg/kg Q8W) with DRd. This part established belamaf 1.9 mg/kg Q8W, extended to Q12W to account as the recommended phase 2 dose (RP2D). Part 2 (dose-expansion phase) evaluates the safety and efficacy of the RP2D in two cohorts Groups A and B, guided by ophthalmologist and hematologist (using Vision-Related Anamnestic, VRA tool), respectively. Results: In Part 1, 24 pts (median age: 73 years; male: 54.2%) entered the study;12.5% had high-risk cytogenetics (HRC). At a median follow-up of 34.3 months, 18 (75%) pts remained on treatment, while 6 (25%) discontinued; 3 (12.5%) death, 1 (4.2%) AE/SAE, 1 (4.2%) withdrew consent, and 1 (4.2%) due to PD. The median dose intensity (MDI) of belamaf was 0.5 mg/kg/Q4W. MRD negativity was achieved in 13 (81.3%) of evaluable patients (n=16). The ORR was 22 (91.7%). Sixteen patients (69.6%) achieved both ≥CR and ≥VGPR. In Part 2 (n=12; median age: 74 years; male: 58.3%),16.7% of pts had HRC. At a median follow-up of 17.9 months, 11 pts (91.7%) remained on treatment; 1 pt (8.3%) discontinued due to PD. Of 113 planned belamaf doses 13 doses were skipped due to OAEs. The MDI was 0.8 mg/kg/Q4W. MRD negativity was achieved in 5 (71.4%) of evaluable patients (n=7). ORR was 11 (91.7%) in evaluable pts. The median time to ≥PR was 1.1 months for both parts. At 18 months, PFS was 91.7% (95% CI 76.4-97.2) and 87.5% (95% CI 66.1-95.8) in the overall and RP2D populations, respectively; corresponding TTP rates were 97.1% (95% CI 80.9-99.6) and 95.5% (95% CI 71.9-99.4). Grade ≥3 BCVA decline was observed in 74(10.4%) of ocular assessments in part 1 and 4(3.9%) and 5(5.3%) in part 2 groups A and B, respectively. Grade ≥2/≥3 keratopathy occurred in 20.2%/0.6% of assessments in Part 1; in Part 2, rates were 6.7%/0% (Group A) and 10.6%/0% (Group B). Median ≥Grade 2 BCVA OAE/keratopathy resolution time was 1.1/1.0 months (Part 1) and 1.9/1.0 months (Part 2). Conclusions: BelaDRd demonstrated robust clinical activity, with rapid and deep responses. Low frequency of ≥Grade 3 OAEs was observed and were rapidly resolved. Moreover, a similar frequency of OAEs was noted when dosing was guided by haematologist vs ophthalmologist ocular assessment. The remarkable PFS supports further evaluation of this quadruplet in a phase 3 study versus other novel quadruplet combinations in NDMM. Clinical trial information: EUCT-2024-515634-32.
Terpos et al. (Thu,) studied this question.