Authored by Ann Liu, PhD
Medically Reviewed by Brian Koffman, MDCM )retired), MSEd
The Bottom Line:
BTK degrader BGB-16673 produced high response rates and was well tolerated in a heavily treated, high-risk group of patients with CLL / SLL.
Who Performed the Research and Where Was it Presented:
Dr. Inhye Ahn from Dana-Farber Cancer Institute and colleagues presented the results at the American Society for Hematology (ASH) Annual Meeting in 2025.
Background:
Bruton tyrosine kinase (BTK) is a key enzyme for the proliferation and survival of chronic lymphocytic leukemia (CLL) / small lymphocytic lymphoma (SLL) cells, and therapies that block the action of BTK have been very successful in treating CLL / SLL. BTK degraders are a new class of drugs that work by completely destroying the BTK protein rather than inhibiting it like BTK inhibitors. BTK degraders bind to BTK and tag it for destruction by the proteosome, which is the cell’s natural garbage disposal. In this study, researchers evaluated a new BTK degrader, BGB-16673.
Methods and Participants:
This is a phase 1/2 clinical trial evaluating the safety and efficacy of BGB-16673 in patients with B-cell cancers. This analysis specifically looked at patients with relapsed / refractory CLL / SLL. BGB-16673 is an oral medication given once per day, and patients received doses between 50 and 500 mg.
Results:
- A total of 67 patients with CLL / SLL enrolled in the study.
- Patients had been treated with a median of four prior lines of therapy, including covalent BTK inhibitors (94%), BCL2 inhibitors (82%), and noncovalent BTK inhibitors (21%).
- Many patients had high-risk features, including deletion 17p and/or TP53 mutations (66%), unmutated IGHV (78%), BTK mutation (38%), and PLCG2 mutation (16%).
- The overall response rate for all dose levels was 86%, and at the 200 mg dose (which is the dose researchers are moving forward with), the overall response rate was 94%.
- At 12 months, 79% of patients were progression-free, and at 18 months, 66% of patients were progression-free.
- Common side effects included fatigue (37%), bruising (31%), diarrhea (28%), and low neutrophil counts (28%).
- Three patients experienced atrial fibrillation (abnormal heart rhythm).
- Four patients died from infections, but this was deemed unrelated to treatment.
Conclusions:
BTK degrader BGB-16673 produced high response rates and was well tolerated in a heavily treated, high-risk group of patients with CLL / SLL. This is very encouraging data, and the early data on progression-free survival is promising.
BGB-16673 is currently being tested in a phase 3 clinical trial for patients with relapsed / refractory CLL / SLL. If you are interested in participating, more information can be found here: A Study to Evaluate the Safety and Efficacy of BGB-16673 Compared to Pirtobrutinib in Adults With Relapsed/Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma.
Links and Resources:
Watch the interview on the abstract here:
You can read the actual ASH abstract here: 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
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