Positive Topline Results Seen for Sonrotoclax in R/R Mantle Cell Lymphoma

BeOne Medicines has announced positive topline results in its phase 1/2 study of sonrotoclax, its next-generation BCL2 inhibitor,¹ in patients with mantle cell lymphoma (MCL), a rare B-cell lymphoma with high unmet need.

In a statement, BeOne said it would submit data to regulatory authorities regarding BGB-11417-201 (NCT05471843), a study of its BCL2 inhibitor in adult patients with relapsed or refractory (R/R) MCL, following treatment with a Bruton tyrosine kinase (BTK) inhibitor and anti-CD20 therapy. BeOne officials said in a statement that full results will be presented at an upcoming scientific meeting.¹

“For people with relapsed or refractory mantle cell lymphoma, 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 R/R MCL, if approved,” Lai Wang, PhD, global head of R&D, BeOne Medicines, said in the statement.¹ “These data add to the remarkable progress we’ve seen over the past 5 years in treating B-cell malignancies, and I’m proud that BeOne has played an impactful role in that transformation with our leading BTK inhibitor.”

MCL is an aggressive type of B-cell non-Hodgkin lymphoma (NHL) that develops in B cells located in the mantle zone of the lymph nodes; it affects about 5% of all patients with NHL and has a 5-year survival rate of about 50%.² BGB-11417-201 is a global, single-arm, multicenter, open-label study that enrolled 125 adult patients with R/R MCL.³ In part 1 of the study, 22 patients received treatment with daily doses of either 160 mg or 320 mg of sonrotoclax to assess the safety and tolerability of the study drug and to identify the recommended dose for part 2, which was 320 mg.

In the second part, 103 patients were enrolled to receive the 320 mg of sonrotoclax following a ramp-up period, to assess the efficacy and safety of sonrotoclax.

The study met its primary end point of overall response rate as assessed by an independent review committee. Investigators demonstrated that treatment with sonrotoclax yielded clinically meaningful responses in this heavily pretreated population. Sonrotoclax also showed promising results across several secondary efficacy end points, including complete response rate, duration of response and progression-free survival.

According to the statement, investigators reported, “The safety profile was generally well-tolerated, and the toxicities were manageable."

Advantages Over Venetoclax

Venetoclax (Venclexta) was the first approved BCL2 inhibitor and is a mainstay in treatment of several blood cancers, including MCL and chronic lymphocytic leukemia (CLL). Sonrotoclax has been found to overcome an important BCL2 mutation seen in patients who develop resistance to venetoclax. It is also more potent, has a stronger binding configuration with BCL2 but a shorter half-life, reducing adverse effects. The risks of tumor lysis syndrome at the start of treatment may be lower than with venetoclax, which could ease administration in community settings.⁴

BeOne officials noted in their statement that new drug applications for sonrotoclax have been accepted in China, and the phase 3 confirmatory CELESTIAL-RR MCL study (BGB-11417-302; NCT06742996) is underway. This trial is evaluating the efficacy and safety of sonrotoclax plus zanubrutinib (Brukinsa), BeOne’s second-generation BTK inhibitor, compared with placebo plus zanubrutinib in adults with R/R MCL.

FDA has previously granted sonrotoclax orphan drug designation in the treatment of patients with MCL, as well as fast track designation for treatment of adult patients with MCL and Waldenström macroglobulinemia (WM). Nearly 2000 patients have been enrolled in trials involving sonrotoclax, according to the statement.

Sonrotoclax has shown promising clinical activity across a range of B-cell malignancies, and nearly 2000 patients have been enrolled to date across the broad global development program. The FDA granted sonrotoclax Fast Track Designation for the treatment of adult patients with MCL.

References

1. BeOne Medicines announces positive topline results for sonrotoclax in relapsed or refractory mantle cell lymphoma (MCL). News release. August 29, 2025. Accessed August 30, 2025. BeOne Medicines. https://ir.beonemedicines.com/news/BeOne-Medicines-Announces-Positive-Topline-Results-for-Sonrotoclax-in-Relapsed-or-Refractory-Mantle-Cell-Lymphoma-(MCL)/9b063914-3787-4b59-95fa-1e0941571f45%20
2. Mantle cell lymphoma. Cleveland Clinic. Reviewed May 8, 2025. Accessed September 4, 2025. https://my.clevelandclinic.org/health/diseases/24030-mantle-cell-lymphoma
3. Study of BGB-11417 monotherapy in participants with relapsed or refractory mantle cell lymphoma. National Cancer Institute. Accessed August 30, 2025. https://www.cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-03138
4. Tam CS, Anderson MA, Lasica M, et al. Combination treatment with sonrotoclax (BGB-11417), a second-generation BCL2 Inhibitor, and zanubrutinib, a Bruton tyrosine kinase (BTK) Inhibitor, is well-tolerated and achieves deep responses in patients with treatment-naïve chronic lymphocytic leukemia/small lymphocytic lymphoma (TN-CLL/SLL): data from an ongoing phase 1/2 study. Blood. 2023;142(suppl 1):Abstr 327. doi:10.1182/blood-2023-179541