Frontline Treatment of Sonrotoclax (BGB-11417) + Zanubrutinib for CLL/SLL Demonstrates High uMRD Rates With Favorable Tolerability: Updated Data From BGB-11417-101, An Ongoing Phase 1/1b Study

Constantine S. Tam, MD, presents updated results from the ongoing phase 1/1b BGB-11417-101 study evaluating frontline sonrotoclax (BGB-11417), a next-generation BCL2 inhibitor, in combination with zanubrutinib in patients with treatment-naïve CLL/SLL. Sonrotoclax was administered following an 8–12-week zanubrutinib lead-in and continued until progression, intolerance, or protocol-defined elective discontinuation at 96 weeks. Across dose levels, the combination demonstrated a 100% overall response rate, with rapid and deep undetectable minimal residual disease (uMRD4) responses that occurred early and deepened over time. In the 320-mg sonrotoclax cohort, best uMRD rates reached 98%, with similar kinetics regardless of IGHV mutation status and no observed disease progression at a median follow-up of 30.7 months. Treatment was generally well tolerated, with mostly low-grade adverse events, no tumor lysis syndrome, and transient neutropenia as the most common grade ≥3 toxicity. These findings support ongoing phase 3 evaluation of sonrotoclax plus zanubrutinib in CELESTIAL-TNCLL.