Dr Opat on Sonrotoclax With Zanubrutinib in Relapsed/Refractory CLL and SLL

Stephen Opat, MBBS, director, Clinical Hematology, head, Department of Hematology, School of Clinical Sciences, Monash Health, Monash University; founder, chair, the Australasian Lymphoma and Related Diseases Registry, lead investigator, the Melbourne Genomics Health Alliance Lymphoma Flagship, discusses the combination of sonrotoclax (BGB-11417) and zanubrutinib (Brukinsa) for patients with relapsed/refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).

Updated findings from the phase 1 BGB-11417-101 study (NCT04277637), which were presented at the 2024 EHA Congress, showcase the efficacy of this combination therapy.

With a median follow-up of 19.3 months (range, 0.4-35.7), the study reported no dose-limiting toxicities, indicating a tolerable safety profile for patients receiving the combination. The maximum tolerated dose (MTD) was not reached, and 320 mg was established as the recommended phase 2 dose (RP2D) for sonrotoclax, Opat states. These findings support the potential for higher doses of sonrotoclax to be safely administered in future studies.

The efficacy of the combination therapy was notable according to Opat, with an overall response rate (ORR) of 97% across all dose levels. This includes a complete response (CR) or CR with incomplete hematologic recovery rate (CRi) of 57%. Notably, in the 320 mg cohort, the ORR was 100%, and the CR/CRi rate was 73%, he explains. These high response rates suggest that the combination of sonrotoclax and zanubrutinib may be highly effective for patients with relapsed/refractory CLL/SLL, Opat reports.

A lack of dose-limiting toxicities and the achievement of deep and durable responses underscore the combination's utility in CLL/SLL. The establishment of 320 mg as the RP2D for sonrotoclax sets the stage for further clinical investigations, including phase 2 studies, to confirm these findings and to explore the long-term benefits and safety of this therapeutic regimen, he imparts.

Opat concludes that the combination of sonrotoclax and zanubrutinib has demonstrated a favorable safety profile and robust efficacy in patients with relapsed/refractory CLL/SLL. These results from the BGB-11417-101 study suggest that this combination could become an important addition to the treatment landscape, pending further validation in subsequent trials, such as the ongoing phase 3, CELESTIAL-TNCLL (NCT06073821), which seeks to assess the combination of sonrotoclax and zanubrutinib vs venetoclax and obinutuzumab for treatment-naïve (TN) CLL, Opat closes.