New data show that the Bruton’s tyrosine kinase (BTK) degrader BGB-16673 produces robust and deepening responses and has a tolerable safety profile in patients with heavily pretreated relapsed or refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), including those with prior BTK inhibitor treatment and BTK mutations.
Although BTK inhibitors have been successful treatments for CLL/SLL, resistance and intolerance present significant challenges. BTK degraders are a new type of targeted therapy. They tag the entire BTK protein for destruction by the cell’s proteasome, rather than just inhibiting it, leading to tumor regression.
The phase 1/2 CaDAnCe-101 trial is assessing one such BTK degrader, BGB-16673, as monotherapy in patients with B-cell malignancies. At the American Society of Hematology Annual Meeting and Exposition, the researchers presented phase 1 safety and efficacy data among a sample of 67 patients with a median age of 67 and median four prior therapies. Eligibility requirements included relapsed or refractory CLL/SLL, at least two prior therapies, and adequate organ function.
Patients received BGB-16673 once daily by mouth. One received 50 mg, 22 received 100 mg, 17 received 200 mg, 15 received 350 mg, and 12 received 500 mg. Of those, 39 patients (58%) remained on treatment until at least data cutoff, with a median follow-up of 18 months.
The media time to first response was 2.8 months, and responses deepened over time.
Overall response rate was 86%, and 4.5% (n = 3) had a complete response (CR) or CR with incomplete marrow recovery rate. ORR was 94% at the 200 mg dose, including one patient with CR.
Almost all patients (96%) experienced treatment-emergent adverse events (TEAEs) of any grade, including fatigue (37%), contusion/bruising (31%), diarrhea (28%), and neutropenia (28%). Grade 3 or higher TEAEs occurred in 62.7% of patients, including neutropenia (24%), pneumonia (10%), and thrombocytopenia (6%). TEAEs led to dose reductions in eight patients (12%), treatment discontinuation in 12 patients (17.9%), and death in four patients (6%). The deaths were related to infection but not determined to be related to treatment.
The authors, led by Inhye Ahn of Dana-Farber Cancer Institute in Boston, Massachusetts, wrote that the 200 mg dose of BGB-16673 is being evaluated in phase 2 and 3 studies in patients with relapsed or refractory CLL/SLL.
Reference
Ahn I, Parrondo R, Thompson M, et al. Updated efficacy and safety results of the Bruton tyrosine kinase (BTK) degrader BGB-16673 in patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) from the ongoing phase 1 CaDAnCe-101 study. Abstract abs25-8349. Presented at: the 67th American Society of Hematology Annual Meeting and Exposition, Dec. 6-9, 2025, Orlando, FL.
