Sonrotoclax (BCL2 inhibitor) + zanubrutinib (BTK inhibitor) drives 99% PB uMRD4 and 100% 30-mo PFS in 1L CLL/SLL

Sonrotoclax (BGB-11417) is a next-generation oral BCL2 inhibitor combined with the oral BTK inhibitor zanubrutinib in the Phase 1/1b BGB-11417-101 study (NCT04277637) in treatment-naive CLL/SLL (sonro 320 mg cohort; n=86; 84 efficacy-evaluable; median follow-up 30.9 months). ORR was 100% with 55% CR; estimated 30-month PFS was 100% with no progressions reported, and best peripheral-blood uMRD4 by flow was 99% (83/84), including 100% (10/10) in TP53-mut/del(17p); NGS best uMRD5 was 86% (66/77). Safety was consistent with BTKi+BCL2i therapy: common TEAEs were neutropenia (38%), contusion (38%), COVID-19 (33%), URTI (30%); grade ≥3 neutropenia occurred in 29%, with no TLS and no AE-related deaths—depth of MRD appears higher than fixed-duration ibrutinib+venetoclax (CAPTIVATE) where best PB uMRD is 75–77% with similar CR rates (55%).