Sonrotoclax Earns FDA Priority Review in R/R Mantle Cell Lymphoma

The FDA has granted priority review to a new drug application (NDA) for sonrotoclax (BGB-11417), a BCL2 inhibitor, for the treatment of patients with relapsed/refractory mantle cell lymphoma (MCL) who experience progression following treatment with a Bruton’s tyrosine kinase (BTK) inhibitor, according to a news release from the developer, BeOne Medicines.¹

Supporting the NDA are data from the phase 1/2 BGB-11417-201 trial (NCT05471843), which showed that treatment with sonrotoclax reached the primary end point of overall response rate (ORR) per independent review committee (IRC) among 125 adult patients with relapsed/refractory MCL. Additionally, promising findings were reported among multiple secondary efficacy end points, including complete response rate, duration of response, and progression-free survival. Furthermore, the agent was found to be well tolerated, and adverse effects were deemed manageable.

The developers plan to present data from the phase 1/2 trial at the 2025 American Society of Hematology (ASH) Annual Meeting and Exposition in Orlando, Florida.

“Sonrotoclax is advancing with remarkable speed, from breakthrough therapy designation to priority review, all within a short window,” Lai Wang, PhD, global head of Research and Development at BeOne, explained in the news release.¹ “That pace reflects both the strength of the data and the urgency of the need for patients with [relapsed/refractory] MCL. With rapid, deep, and durable responses and a manageable safety profile, sonrotoclax is emerging as a potential best-in-class BCL2 inhibitor, alongside our 2 other transformative hematology assets—BTK inhibitor zanubrutinib [Brukinsa], and investigational BTK degrader BGB-16673.”

In the trial, patients were treated in 2 parts, the first of which assessed the safety and tolerability, maximum tolerated dose, and recommended phase 2 dose (RP2D) of sonrotoclax; the second assessed the BCL2 inhibitor at a ramp-up schedule of the RP2D.² In part 1 of the study, patients received 160 mg or 320 mg of the agent, and 320 mg was identified as the RP2D.

According to the developers, sonrotoclax has shown high potency and specificity as an inhibitor for BCL2 with a short half-life and no drug accumulation.³ This agent is among a class of drugs called BH3 mimetics, which emulate natural cell death signals. Additionally, the FDA had previously granted the agent fast track designation for the treatment of adult patients with MCL and Waldenström macroglobulinemia.

Patients eligible for enrollment on the trial had histological confirmation of MCL, had received at least 1 line of anti-CD20–based immune or chemoimmunotherapy, had relapsed/refractory disease, and had the presence of measurable disease. Inclusion criteria also encompassed having an availability of archival tissue confirming MCL diagnosis or a willingness to undergo fresh biopsy; an ECOG performance status of 0, 1, or 2; and adequate organ function.

Additionally, those ineligible for enrollment in the trial had central nervous system-involved lymphoma, any prior malignancy other than MCL in the past 3 years, previous BCL2 inhibitor exposure, or a prior autologous stem cell transplantation within 3 months of study start. Furthermore, those with clinically significant cardiovascular disease; a major surgery or injury within 4 weeks of study start; or any active fungal, bacterial, or viral infection requiring systemic treatment were deemed ineligible for enrollment.

“For [patients] with relapsed or refractory [MCL], the disease is aggressive, the treatment landscape fragmented, and the outcomes unacceptably poor. These topline results for sonrotoclax underscore its potential to deliver meaningful and durable responses and offer the first BCL2 inhibitor for patients with [relapsed/refractory] MCL, if approved,” Wang explained in a release on an announcement of topline data from the phase 1/2 trial.³

References

1. 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 November 26, 2025. https://tinyurl.com/hs9spxef
2. Study of BGB-11417 monotherapy in participants with relapsed or refractory mantle cell lymphoma. ClinicalTrials.gov. Updated September 9, 2025. Accessed November 26, 2025. https://tinyurl.com/7m6x8f5p
3. BeOne Medicines announces positive topline results for sonrotoclax in relapsed or refractory mantle cell lymphoma (MCL). News release. BeOne Medicines. August 29, 2025. Accessed November 26, 2025. https://tinyurl.com/bdd5mty2