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Sonrotoclax + zanubrutinib for patients with R/R MCL: Results from the phase I BGB-11417-101 trial

By Dylan Barrett

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Jul 24, 2025

Learning objective: After reading this article, learners will be able to cite a new clinical development in mantle cell lymphoma



Combination therapy consisting of venetoclax (a B-cell lymphoma 2 inhibitor; BCL-2i) and ibrutinib (a Bruton’s tyrosine kinase inhibitor; BTKi) has shown efficacy in patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL).1 Sonrotoclax is a next-generation BCL-2i that has demonstrated more selectivity and pharmacologic potency compared with venetoclax.1 Sonrotoclax also has a shorter half-life compared with venetoclax and no drug accumulation.1 Zanubrutinib, a second-generation BTKi, has shown favorable safety and efficacy and is approved by the U.S. Food and Drug Administration (FDA) for the treatment of patients with R/R MCL.1

The ongoing phase I/Ib BGB-11417-101 trial (NCT04277637) is evaluating the safety and efficacy of sonrotoclax  ± zanubrutinib ± obintuzumab, in patients with B-cell malignancies.1 Updated results from the cohort of patients with R/R MCL who received sonrotoclax + zanubrutinib (N = 51) were presented at the 2025 European Hematology Association (EHA) Congress by Raul Cordoba.1

Key learnings

The safety profile was consistent across all sonrotoclax doses tested, with no DLTs, and the MTD was not reached up to sonrotoclax 640 mg; sonrotoclax 320 mg was chosen as the RP2D (any TEAEs, 96.3%; Grade ≥3 TEAEs, 51.9%).

With a median follow-up of 16.4 months, the ORR and CR rate were 78% and 70%, respectively, in the sonrotoclax 320 mg + zanubrutinib group (n = 23). 

The median DoR in the sonrotoclax 320 mg + zanubrutinib group was not reached, with a 24-month DoR rate of 80.1%. 

Sonrotoclax + zanubrutinib had a tolerable safety profile and encouraging antitumor activity, with early, deep, and durable responses in patients with R/R MCL. This combination is being evaluated in the phase III CELESTIAL-RRMCL trial (NCT06742996), with enrollment currently ongoing. 

BCL-2i, B-cell lymphoma 2 inhibitor; BTKi, Bruton’s tyrosine kinase inhibitor; CR, complete remission; DLT, dose-limiting toxicity; DoR, duration of response; EHA, European Hematology Association; MCL, mantle cell lymphoma; MTD, maximum tolerated dose; ORR, overall response rate; RP2D, recommended phase II dose; R/R, relapsed/refractory; TEAE, treatment-emergent adverse event. 

References

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