FDA Approves Sonrotoclax in Relapsed/Refractory Mantle Cell Lymphoma

The News

The FDA has granted accelerated approval to sonrotoclax (Beqalzi) as a treatment for patients with relapsed/refractory mantle cell lymphoma (MCL) who experienced progression following treatment with at least 2 lines of prior systemic therapy, including a Bruton’s tyrosine kinase (BTK) inhibitor, according to a press release from the agency.¹

Supporting Data

The approval for sonrotoclax was supported by findings from the phase 1/2 BGB-11417-201 trial (NCT05471843) evaluating the agent among patients with MCL who received prior anti-CD20-based therapy and BTK inhibition.

According to data published in Blood and presented at the 2025 American Society of Hematology (ASH) Annual Meeting and Exposition, after a median follow-up of 14.2 months (range, 0.3-24.9), the objective response rate (ORR) per independent review committee (IRC) assessment was 52.4% (95% CI, 42.4%-62.4%; P <.0001) among patients treated in the part 2 portion of the study at the recommended phase 2 dose (RP2D) of 320 mg once each day.² Additionally, the complete response (CR) rate was 15.5% (95% CI, 9.1%-24.0%) per IRC evaluation, and the median time to response (TTR) was 1.9 months (range, 1.6-6.2).

Additionally, among patients treated at the RP2D in the second portion of the trial, the median duration of response (DOR) was 15.8 months (95% CI, 7.4-not evaluable [NE]) by IRC assessment, with 63% of patients remaining in remission after 9 months. Additionally, the median progression-free survival (PFS) and overall survival (OS) per IRC assessment was 6.5 months (95% CI, 4.0-10.4) and not reached (NR; 95% CI, 14.8-NE), respectively.

Phase 1/2 BGB-11417-201 Trial Design

The coprimary end points of the phase 1 portion of the trial included dose-limiting toxicities (DLTs), adverse effects (AEs), and tumor lysis syndrome (TLS). In the phase 2 portion of the trial, the primary end point was IRC-assessed ORR. Secondary end points across both parts of the trial included DOR, PFS, and TTR per IRC assessment, investigator-assessed ORR, OS, and health-related quality of life. Among patients treated with the investigational agent in the phase 2 portion of the trial.

Those with histologically confirmed MCL per World Health Organization 2016 classification who received at least 1 prior line of anti-CD20–based therapy and prior BTK inhibition, with no history of BCL2 inhibition and an ECOG performance status of 0 to 2, were included for enrollment on the trial. Patients must also have had relapsed/refractory disease, had availability of archival tissue confirming MCL diagnosis or a willingness to undergo fresh biopsy, and adequate organ function.

In the trial, patients were treated in 2 parts, the first of which assessed the safety and tolerability, maximum tolerated dose, and RP2D of sonrotoclax; the second assessed the BCL2 inhibitor at a ramp-up schedule of the RP2D. In part 1 of the study, patients received 160 mg or 320 mg of the agent, and 320 mg was identified as the RP2D. Patients in the efficacy expansion portion received the RP2D until disease progression, whereas the safety expansion cohort treated up to 2 cohorts at select dose levels for a maximum of 12 patients in each.

The median age at the February 4, 2025, cutoff among patients who received sonrotoclax at the RP2D (n = 115) was 68 years (range, 39-85). A total of 64.3% of patients were at least 65 years old, 75.7% were male, 53.0% were White, and 75.7% were not Hispanic or Latino. Most patients had an ECOG performance status of 1 (64.3%), stage IV disease at study entry (78.3%), and were refractory to their last line of treatment (87.0%).

Among patients assessed in the safety run-in for the phase 1 portion of the trial, no DLTs were observed, and a maximum tolerated dose was not found. Across the safety population (n = 115), treatment emergent AEs (TEAEs) of any-grade occurred in 96.5%, and treatment-related AEs (TRAEs) occurred in 80.0% of patients.

Moreover, grade 3 or higher TEAEs and TRAEs were reported in 52.2% vs 36.5% of patients, with serious TEAEs occurring in 37.4%. TEAEs leading to death, treatment discontinuation, or treatment modification were observed in 13.0%, 13.9%, and 27.0% of patients, respectively.

Common any-grade TEAEs included neutropenia (35.7%), thrombocytopenia (24.3%), and anemia (24.3%). Any-grade infections, TLS, and febrile neutropenia were reported in 39.1%, 7.0%, and 1.7% of patients, respectively. Among the patients who experienced TLS, 2 had clinical and 6 had laboratory TLS; all events were resolved without sequelae, and no deaths or discontinuations occurred due to an event.

Prescribing information contains warnings and precautions for tumor lysis syndrome, serious infections, and neutropenia.

In November 2025, the FDA granted priority review to a new drug application (NDA) for sonrotoclax in this relapsed/refractory MCL population.³

References

1. FDA grants accelerated approval to sonrotoclax for relapsed or refractory mantle cell lymphoma. News release. FDA. May 13, 2026. Accessed May 13, 2026. https://tinyurl.com/3jbzuu75
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
3. U.S. FDA grants priority review to sonrotoclax for the treatment of relapsed or refractory mantle cell lymphoma. News release. BeOne Medicines. November 26, 2025. Accessed March 9, 2026. https://tinyurl.com/hs9spxef