Recruiting Trial: Sonrotoclax Plus Zanubrutinib for CLL

Authored by Ann Liu, PhD

The Bottom Line:

An ongoing phase 3 study is comparing the efficacy of sonrotoclax plus zanubrutinib with acalabrutinib plus venetoclax in patients with previously untreated CLL.

Who Performed the Research and Where Was it Presented:

Dr. Mazyar Shadman from Fred Hutchinson Cancer Center and colleagues presented the study design at the American Society of Clinical Oncology (ASCO) Annual Meeting in 2026.

Background:

Treatments that combine a BTK inhibitor and a BCL2 inhibitor have emerged as effective fixed-duration therapies for chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). Sonrotoclax is an experimental, next-generation BCL2 inhibitor that is more selective and potent than venetoclax. Results from a phase 1/1b clinical trial testing the combination of sonrotoclax and zanubrutinib showed very promising results with high rates of undetectable measurable residual disease. Now sonrotoclax plus zanubrutinib is being tested in larger phase 3 clinical trials.

Methods and Participants:

• BGB-11417-304 is a global, phase 3 clinical trial comparing the efficacy of sonrotoclax plus zanubrutinib with the approved combination of acalabrutinib plus venetoclax.
• Patients are eligible if they have been diagnosed with CLL and have not received prior treatment.
• Patients will be randomly assigned to receive either sonrotoclax plus zanubrutinib or acalabrutinib plus venetoclax. The study is open-label, so patients will know what treatment they are receiving.
• For both treatments, there will be a 2-3 cycle lead-in period of BTK inhibitor alone, followed by 12 cycles of combination BTK inhibitor plus BCL2 inhibitor.
• The primary outcome is progression-free survival (how long before the disease gets worse).
• Undetectable measurable residual disease in the blood and bone marrow will be measured at end of therapy as an intermediate endpoint.

Conclusions:

This study will test whether the combination of sonrotoclax and zanubrutinib has similar or better efficacy and safety than the already approved combination of acalabrutinib plus venetoclax for first-line treatment of CLL. Sonrotoclax is already approved in mantle cell lymphoma. This phase 3 trial hopes to make CLL another FDA-approved indication.

Links and Resources:

You can read the actual ASCO abstract here: Sonrotoclax (BGB-11417) + zanubrutinib (SZ) vs venetoclax + acalabrutinib (AV) in treatment-naive chronic lymphocytic leukemia (TN CLL): A phase 3 randomized trial design (CELESTIAL-TNCLL-2)

Take care of yourself first.

Ann Liu, PhD