Dr Shadman on uMRD Rates With Sonrotoclax Plus Zanubrutinib in Frontline CLL/SLL

“The study is important in [terms of] generating the hypothesis that sonrotoclax plus zanubrutinib may be the most effective oral combination [in this patient population].”

Mazyar Shadman, MD, MPH, a professor in the Clinical Research Division, the deputy chief medical officer, the medical director of Cellular Immunotherapy, and the Innovators Network Endowed Chair at Fred Hutch Cancer Center, discussed undetectable minimal residual disease (MRD) rates with sonrotoclax (Beqalzi) and zanubrutinib (Brukinsa) in patients with treatment-naive chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), including those with high-risk cytogenetics, from the phase 1/1b BGB-11417-101 trial (NCT04277637). These data were presented at the 2026 ASCO Annual Meeting.

Early findings from BGB-11417-101 demonstrated highly encouraging activity in the frontline treatment setting, generating considerable interest in the potential of this all-oral regimen for patients with CLL/SLL, Shadman began. One of the most notable findings from the study was the exceptionally high rate of uMRD in the 320-mg cohort (n = 56), which reached 98.2% by week 96 at a 10^-4 sensitivity, he underscored.

These results are particularly significant when considered in the context of previously studied combinations involving venetoclax (Venclexta) and BTK inhibitors, Shadman explained. With those regimens, uMRD rates have generally been reported in the range of 30% to 40%, he continued. The markedly higher rate observed with sonrotoclax plus zanubrutinib raises the possibility that deeper remissions may translate into more durable clinical benefits, including prolonged progression-free survival and extended time to next treatment, he said.

The phase 1b study has primarily served as a hypothesis-generating trial, supporting the concept that sonrotoclax and zanubrutinib may represent one of the most effective oral doublet regimens currently under development, Shadman said. The promising efficacy signals observed thus far have laid the foundation for additional clinical studies designed to further evaluate the combination and determine its role in the treatment landscape, he concluded.