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FDA grants accelerated approval to sonrotoclax for relapsed/refractory MCL

On May 13, 2026, the U.S. Food and Drug Administration (FDA) granted accelerated approval to sonrotoclax for adults with relapsed/refractory (R/R) mantle cell lymphoma (MCL) after at least two prior lines of therapy, including a Bruton’s tyrosine kinase inhibitor (BTKi).1

MCL is a rare and aggressive subtype of B-cell non-Hodgkin lymphoma (NHL), characterized by a pattern of continued relapse in a large proportion of patients.2  Although treatment options continue to expand and patient outcomes are improving, the management of patients who relapse following frontline treatment and BTKi therapy remains a challenge, particularly those who are not eligible for CAR T-cell therapy.2 Therefore, additional therapeutic options are needed for this subset of patients.

Sonrotoclax is a potent and selective second-generation B-cell lymphoma 2 (BCL2) inhibitor that has demonstrated efficacy against venetoclax-resistant BCL2 mutants in both in vitro and in vivo settings.3 The approval of sonrotoclax is supported by early findings from the ongoing Phase I/II BGB-11417-201 trial (NCT05471843), which were presented at the 67th ASH Annual Meeting and Exposition by Michael Wang, MD, from The University of Texas MD Anderson Cancer Center, Houston, TX.2 In the 103 efficacy-evaluable patients, the overall response rate (ORR) as per the 2014 Lugano classification was 52% (95% CI: 42–62), and the study met its primary endpoint.1 The median time to response was 1.9 months (range: 1.6–6.5 months), and after an estimated median follow-up of 11.9 months, the median duration of response (DOR) was 15.8 months (95% CI: 7.4–not estimable), indicating clinically meaningful benefits with this agent.1,2 

Regarding safety, treatment-emergent adverse events (TEAEs) of any grade were reported in ≥20% of the 115 patients evaluable for safety, with 36.5% experiencing a serious TEAE.2 In general, the safety data indicated that sonrotoclax monotherapy at a dose of 320 mg once daily is well tolerated.2 To reduce the risk of tumor lysis syndrome (TLS), the recommended sonrotoclax dosing regimen begins with a four-week ramp-up phase followed by 320 mg once daily until disease progression or unacceptable toxicity.1   

We spoke with Prof. Wang to gain insight into the value of sonrotoclax and how it differs from the first-generation BCL2 inhibitor venetoclax. Prof. Wang states that “Sonrotoclax … has 14-fold higher enzymatic activity in the test tube compared with venetoclax. It is not only more potent but also more specific – it is six times more selective than venetoclax. And venetoclax has a half-life of 26 hours, so [often] the side effects can last [a long time]. For example, one of the new side effects…is tumor lysis syndrome, we call it TLS, and we have to monitor for TLS because the half-life is so long and there’s a lot of accumulation of the drug in the system. However, sonrotoclax has a half-life of only five hours, so there’s a lack of human system accumulation. Therefore, the need to monitor TLS is much less, and maybe the side effects could be improved.”

In conclusion, the approval of sonrotoclax represents an important advance for patients with R/R MCL, particularly those with prior BTKi exposure, for whom treatment options remain limited, and outcomes are often poor. As the first BCL2 inhibitor approved in this setting, sonrotoclax introduces a novel targeted mechanism with the potential to deliver rapid, durable responses and expand the therapeutic armamentarium for heavily pretreated patients.

References

  1. U.S. Food and Drug Administration. FDA grants accelerated approval to sonrotoclax for relapsed or refractory mantle cell lymphoma. Available here. (Last accessed 14/05/2026)
  2. Wang M, Song Y, Hermine O, et al. Sonrotoclax (BGB-11417) monotherapy in patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL) previously treated with a bruton tyrosine kinase (BTK) inhibitor: early results from a phase 1/2 study. Blood. 2025 Nov;146(suppl 1):663.
  3. Liu J, Li S, Wang Q, et al. Sonrotoclax overcomes BCL2 G101V mutation-induced venetoclax resistance in preclinical models of hematologic malignancy. Blood. 2024 May;143(18):1825-1836.

Written by Natalie Markova

Reviewed by Anya Dragojlovic Kerkache