Sonrotoclax Meets Primary ORR End Point in Mantle Cell Lymphoma

Sonrotoclax additionally exhibited a promising complete response rate, duration of response, and progression-free survival, encompassing multiple secondary efficacy end points.

Sonrotoclax exhibited favorable efficacy and safety outcomes in adult patients with relapsed/refractory mantle cell lymphoma (MCL) following progression on a Bruton’s tyrosine kinase (BTK) inhibitor and anti-CD20 therapy, according to a news release from the drug’s developer, BeOne Medicines Ltd.¹

Specifically, in the phase 1/2 BGB-11417-201 trial (NCT05471843), the investigational agent met its overall response rate (ORR) primary end point, assessed per independent review committee (IRC). Furthermore, sonrotoclax additionally exhibited a promising complete response (CR) rate, duration of response (DOR), and progression-free survival (PFS), encompassing multiple secondary efficacy end points.

Regarding safety data, sonrotoclax was generally well-tolerated in this heavily pretreated patient population, and emergent toxicities were manageable.

The developers plan to present the full data from the phase 1/2 trial at an upcoming medical meeting. Additionally, they anticipate submitting these findings to global regulatory bodies, including the FDA, for approval in patients with relapsed/refractory MCL. Furthermore, the phase 3 confirmatory CELESTIAL-RR MCL/BGB-11417-302 trial (NCT06742996) enrolled its first patient earlier this year and is currently ongoing.

Sonrotoclax was previously granted orphan drug designation by the FDA for the treatment of patients with MCL, and fast track designation for the treatment of patients with MCL and Waldenström macroglobulinemia. New drug applications for sonrotoclax in the aforementioned MCL population and relapsed/refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) populations have been accepted and are under review by the Center for Drug Evaluation of the China National Medicine Products Administration (NMPA).

“For [patients] with relapsed/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 [B-cell lymphoma 2 (BCL2)] inhibitor for patients with [relapsed/refractory] MCL, if approved,” Lai Wang, PhD, global head of Research and Development at BeOne Medicines, explained in the news release.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.”

The global, multicenter, single-arm, phase 1/2 trial enrolled 125 adult patients and treated them across 2 study parts. In part 1, patients (n = 22) received 160 mg or 320 mg of sonrotoclax to assess its safety and tolerability and identify a recommended part 2 dose. Part 2 saw patients (n = 103) treated with the recommended daily dose of 320 mg of sonrotoclax after ramp-up dosing, to assess its efficacy as well as safety in patients with relapsed/refractory MCL following progression on a BTK inhibitor and anti-CD20 therapy.

The developers engineered sonrotoclax as a next-generation investigational BCL2 inhibitor. Part of a group of drugs called BH3 mimetics, which emulate natural cell death signals, laboratory and early drug development studies have shown high potency and specificity with the drug, as well as a short half-life and no drug accumulation.

Patients eligible for enrollment on the phase 1/2 trial included those with histological confirmation of MCL, presence of measurable disease, an ECOG performance status of 0 to 2, and adequate organ function.² Those with central nervous system involvement by lymphoma, those with prior malignancies other than MCL within the past 3 years, those with prior BCL-2 inhibitor exposure or autologous stem cell transplantation within the last 3 months, and those with clinically significant cardiovascular disease were among patients ineligible for enrollment on the trial.

Reference

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