Phase 3 Trial Evaluates Sonrotoclax Plus Zanubrutinib vs SOC in CLL

Mazyar Shadman, MD, MPH, Innovators Network Endowed Chair, associate professor, Clinical Research Division, Fred Hutch Cancer Center; associate professor, Medical Oncology Division, University of Washington School of Medicine, discusses the mechanism of action of sonrotoclax (BGB-11417), a novel BCL2 inhibitor, and the phase 3 trial titled CELESTIAL-TNCLL (NCT06073821), which is evaluating the agent for the treatment of patients with chronic lymphocytic leukemia (CLL).

CELESTIAL-TNCLL is a randomized, open-label, phase 3 study (NCT06073821) where investigators are assessing sonrotoclax in combination with zanubrutinib (Brukinsa) compared with standard venetoclax (Venclexta) and obinutuzumab (Gazyva) for the treatment of patients with chronic lymphocytic leukemia (CLL). Shadman discussed the rationale and study design of CELESTIAL-TNCLL at the 2024 ASCO Annual Meeting.

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0:09 | Sonrotoclax is a novel BCL2 inhibitor. As we know, currently, we only have 1 drug in this family: Venetoclax. Venetoclax in combination with anti-CD20 antibodies or by itself has been standard-of-care for CLL in the frontline and relapse settings. Sonrotoclax is a next-generation BCL2 inhibitor. In preclinical studies, it shows higher efficacy compared [with] venetoclax, and also has a short half-life, which gives us the opportunity of being more flexible in terms of the ramp-up schedule.

0:40 | We have a lot of experience combining BTK inhibitors with BCL2 inhibitors. With ibrutinib [Imbruvica] and venetoclax, there are now a number of clinical trials that have shown the efficacy and also acceptable safety profile with the combination. So the idea here is to use a next-generation BTK inhibitor, zanubrutinib, which in head-to-head trials compared [with] ibrutinib, has shown superior efficacy and safety. In addition, as I mentioned, sonrotoclax is believed to be potentially a more effective BCL2 inhibitor. Given the differences of the modes of action, the 2 drugs can be combined. In this study, we are comparing the combination of sonrotoclax and zanubrutinib to the standard-of-care, venetoclax and obinotuzmab.