Phase I/Ib BGB-11417-101 trial: Sonrotoclax + zanubrutinib in TN CLL/SLL

Results from the phase I/Ib BGB-11417-101 (NCT04277637) study evaluating sonrotoclax + zanubrutinib in 137 patients with treatment-naïve (TN) chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL/SLL) were presented by Chan Y. Cheah at the European Hematology Association (EHA) 2026 Congress, June 11–14, 2026, Stockholm, SE. Patients received zanubrutinib + either sonrotoclax 160 mg (n = 51) or 320 mg (n = 86). The primary objectives were to determine the recommended phase II dose (RP2D) and to evaluate safety and tolerability. 

Key data: Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 68.6% of patients in the sonrotoclax 160 mg group vs 60.5% of patients in the 320 mg group. Serious TEAEs occurred in 39.2% vs 31.4% of patients, with no tumor lysis syndrome (TLS) or TEAEs leading to death in either dose group. Neutropenia was the most common Grade ≥3 TEAE (160 mg, 24%; 320 mg, 31%). The overall response rates (ORRs) were 100% in both dose groups, with complete responses (CRs) in 51.0% vs 59.5% of patients. Sonrotoclax 320 mg was selected as the RP2D. The 24-month progression-free survival (PFS) rate in the 320 mg group was 100%. Undetectable measurable residual disease at 10⁻⁴(uMRD4) rates increased from 81.2% at Week 24 to 98.2% at Week 96. At Week 96, uMRD4 rates were 91.7% and 96.8% in patients with mutated immunoglobulin heavy chain variable (IGHV) and unmutated IGHV, respectively, and 92.9% and 97.7% in patients with mutated TP53/del(17p) and no TP53 mutation/del(17p), respectively.  

Key learning: Sonrotoclax 320 mg + zanubrutinib demonstrated high response rates in patients with TN CLL/SLL, with rates of uMRD4 negativity >90%, including in patients with high-risk disease, and the safety profile was manageable. This combination is being further investigated in phase III trials in TN CLL (NCT06073821 and NCT07277231) and relapsed/refractory (R/R) mantle cell lymphoma (MCL; NCT06742996).