Results: As of May 16, 2025, a total of 20 patients were enrolled and had been treated in 1 of 3 cohorts: sonrotoclax 320 mg + K56 + dex (n=11), sonrotoclax 320 mg + K70 + dex (n=7), or sonrotoclax 640 mg + K56 + dex (n=2; enrollment ongoing). The median follow-up in all patients was 7.3 months (range, 1.7-22.2 months). Across cohorts, the median age was 65 years (range, 51-77 years), 75% were male, and 50% were White. Patients had a median of 4 prior lines of therapy (range, 2-8); 65% of patients had ≥4 prior lines, 85% were triple-class exposed, and 20% were triple-class refractory. At data cutoff, 13 patients (65%) remained on study treatment; 6 patients discontinued due to disease progression, and 1 withdrew consent. The most common all-grade treatment-emergent adverse events (TEAEs) were insomnia (40%), fatigue (35%), nausea (30%), anemia (30%), and back pain (30%). Grade ≥3 TEAEs occurred in 12 patients (60%), grade ≥3 hematologic TEAEs occurred in 7 (35%), and grade ≥3 infections occurred in 5 (25%). Cardiac disorders occurred in 3 patients (15%; grade 2 arrhythmia, n=1; grade 2 atrial flutter, n=1; grade 1 tachycardia, n=1), and hypertension in 4 patients (20%; grade 1/2, n=2; grade 3, n=2). Eight patients (40%) experienced a serious TEAE; the most common serious TEAE was pneumonia (15%). Dose-limiting toxicities were reported in 2 patients (transient grade 3 thrombocytopenia and acute kidney injury). No TEAEs led to death, sonrotoclax discontinuation, or sonrotoclax dose reduction. Four patients died during the study, all for reasons unrelated to study treatment. In 19 response-evaluable patients across dose groups, the ORR was 84% (95% CI, 60%-97%), which included 32% (95% CI, 13%-57%) of patients with a complete response (CR)/stringent complete response (sCR). The median time to response was 1.0 months (range, 0.9-6.1 months). Median duration of response and median progression-free survival were not reached.

Conclusions: Sonrotoclax + K + dex combination therapy demonstrated a tolerable safety profile and encouraging antimyeloma activity, with an 84% ORR and a 32% CR/sCR rate in heavily pretreated patients with t(11;14)-positive R/R MM. Enrollment in BGB-11417-105 is ongoing, and additional treatment combinations with sonrotoclax are being investigated.