FDA Approves Sonrotoclax for Relapsed/Refractory Mantle Cell Lymphoma

The FDA has granted accelerated approval to sonrotoclax (Beqalzi) for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least 2 lines of systemic therapy, including a Bruton tyrosine kinase (BTK) inhibitor.¹

The approval was supported by data from the phase 1/2 BGB-11417-201 trial (NCT05471843), which showed that patients with relapsed/refractory MCL who were previously treated with an anti-CD20–based therapy and a BTK inhibitor (n = 103) experienced an overall response rate (ORR) of 52% (95% CI, 42%-62%) and a median time to response of 1.9 months. At a median follow-up of 11.9 months, the median duration of response was 15.8 months (95% CI, 7.4-not estimable).

Regarding safety (n = 115), serious adverse effects were reported in 37% of patients, with pneumonia being the most common (10%). The prescribing information for sonrotoclax includes warnings and precautions for tumor lysis syndrome (TLS), serious infections, and neutropenia.

Sonrotoclax dosing is recommended to begin with a 4-week ramp-up phase to reduce the risk of TLS, followed by 320 mg once per day until disease progression or unacceptable toxicity.

What did previous data from BGB-11417-201 show about efficacy in this setting?

Findings presented at the 2025 American Society of Hematology (ASH) Annual Meeting and Exposition showed that at a median follow-up of 14.2 months (range, 0.3-24.9) for patients treated at the recommended phase 2 dose of 320 mg once per day (n = 103), the ORR was 52.4% (95% CI, 42.4%-62.4%), including a complete response (CR) rate of 15.5% (95% CI, 9.1%-24.0%).²

Notably, among patients who received fewer than 3 prior lines of therapy, the ORR was 61.0% (95% CI, 44.5%-75.8%).

What did the trial reveal about sonrotoclax’s safety and tolerability?

Data presented at ASH 2025 also showed that in the safety-evaluable population for the 320-mg dose (n = 115), any-grade treatment-emergent adverse effects (TEAEs) were reported in 96.5% of patients, with treatment-related TEAEs occurring in 80.0%. Grade 3 or higher TEAEs and treatment-related TEAEs occurred at rates of 52.2% and 36.5%, respectively.

TEAEs led to death in 13.0% of patients, treatment discontinuation in 13.9% of patients, dose interruption in 27.0% of patients, and dose reduction in 0.9% of patients.

The most common TEAEs comprised neutropenia (any grade, 35.7%; grade ≥ 3, 19.1%), thrombocytopenia (24.3%; 9.6%), anemia (24.3%; 7.8%), decreased white blood cell count (21.7%; 2.6%), hyperuricemia (19.1%; 0%), hypokalemia (17.4%; 0%), pneumonia (15.7%; 10.4%), diarrhea (13.9%; 4.3%), increased aspartate amintransferase levels (12.2%; 0.9%), increased alanin aminotransferase levels (10.4%; 0%), constipation (10.4%; 0%), and lymphopenia (10.4%; 0%).

Any-grade infections were reported in 39.1% of patients, including 16.5% who experienced grade 3 or higher infections. Any-grade and grade 3 or higher febrile neutropenia were each reported in 1.7% of patients. TLS of any grade and grade 3 or higher occurred in 7.0% of patients.

What was the design of the BGB-11417-201 trial?

The dose-escalation and -expansion study enrolled patients at least 18 years of age with histologically confirmed MCL who had received at least 1 prior line of anti-CD20–based therapy and at least 1 prior BTK inhibitor. Patients needed to have an ECOG performance status of 0 to 2, and no prior treatment with a BCL-2 inhibitor was allowed.

No dose-limiting toxicities were reported during dose escalation. The 320-mg dose was evaluated in the dose-expansion phase.

During dose expansion, ORR per independent review committee assessment served as the trial’s primary end point.

References

1. FDA grants accelerated approval to sonrotoclax for relapsed or refractory mantle cell lymphoma. FDA. May 13, 2026. Accessed May 13, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-sonrotoclax-relapsed-or-refractory-mantle-cell-lymphoma
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;146(suppl 1):663. doi:10.1182/blood-2025-663