Promising BCL2 Inhibitor Shows Efficacy in Relapsed Mantle Cell Lymphoma

The phase 1/2 BGB-11417-201 study (NCT05471843) has demonstrated that sonrotoclax, an investigational next-generation BCL2 inhibitor, achieved its primary end point of overall response rate (ORR) in a heavily pretreated population of adult patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL).¹ The positive topline results suggest sonrotoclax may represent a new therapeutic option for patients with this aggressive and challenging B-cell malignancy.

Mantle cell lymphoma, a rare and aggressive subtype of B-cell non-Hodgkin lymphoma, often presents at an advanced stage, with nearly all patients eventually experiencing refractory or relapsed disease. While treatment options for MCL have expanded, outcomes for patients with R/R disease remain poor, with a 5-year survival rate of approximately 50%. The current data for sonrotoclax indicate a potential for clinically meaningful and durable responses in a population that has progressed following prior treatment with an anti-CD20 therapy and a BTK inhibitor.

“For [patients] 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,” said Lai Wang, PhD, Global Head of Research and Development, BeOne Medicines, in a press release. “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 study was a global, multicenter, single-arm, open-label trial that enrolled 125 adult patients with R/R MCL.^1,2 The patient cohort was defined by previous treatment with an anti-CD20 therapy and a BTK inhibitor, underscoring the advanced nature of the disease in this population. The study was structured in 2 parts: an initial dose-finding phase (part 1) followed by an expansion cohort at the recommended dose (part 2). In part 1, 22 patients received either 160 mg or 320 mg of sonrotoclax daily to assess safety and tolerability. The recommended dose of 320 mg was then administered daily, following a ramp-up schedule, to 103 patients in part 2.

The primary end point of ORR, as assessed by an independent review committee, was successfully met. Furthermore, the study also demonstrated encouraging results across several key secondary end points, including complete response rate, duration of response, and progression-free survival. The safety profile of sonrotoclax was reported to be generally well-tolerated, with manageable toxicities. These data suggest the potential for sonrotoclax as a monotherapy in a patient population with significant unmet medical needs.

BeOne Medicines plans to submit these data to the US FDA and other global regulatory bodies for potential approval.

The FDA has previously granted sonrotoclax orphan drug designation for the treatment of MCL and fast track designation for both MCL and Waldenström macroglobulinemia, which may expedite the regulatory review process. In China, new drug applications for sonrotoclax in R/R MCL and R/R chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are already under review by the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) for potential accelerated approval.

The BGB-11417-201 study is part of a broader development program for sonrotoclax, which includes a phase 3 confirmatory CELESTIAL-RR MCL study (BGB-11417-302; NCT06742996) that is currently enrolling patients. The extensive clinical program for sonrotoclax, which includes studies in a range of B-cell malignancies, has enrolled nearly 2000 patients to date.

FAQs

What is sonrotoclax?

Sonrotoclax (BGB-11417) is an investigational small molecule B-cell lymphoma 2 (BCL2) inhibitor. It is currently being developed for the treatment of various hematologic cancers.

How does sonrotoclax work to combat cancer cells?

Sonrotoclax works by targeting the BCL2 protein, which is a key regulator of a cellular death program called apoptosis. Many cancer cells produce abnormally high amounts of BCL2, which prevents the natural apoptosis process from occurring, allowing these cancer cells to survive. Sonrotoclax is designed to bind to BCL2, preventing it from blocking the apoptosis signals. By removing this BCL2 blockade, the cellular self-destruction protocol is restored, leading to the destruction of cancer cells.

Can sonrotoclax be used with other cancer treatments?

Yes, sonrotoclax has the potential to work in conjunction with other cancer drugs. Many existing cancer treatments function by triggering apoptosis. By inhibiting BCL2, sonrotoclax can potentially enhance the effectiveness of these other cancer drugs, making them more potent in inducing cancer cell death.

Is sonrotoclax currently available for patient use?

No, sonrotoclax is an investigational drug. This means that its safety and efficacy have not yet been fully established, and it is not yet approved for clinical use. It is currently undergoing clinical development.

In what stage of development is sonrotoclax, and what types of cancers is it being evaluated for?

Sonrotoclax is currently in clinical development for various hematologic cancers. It is being evaluated both as a standalone monotherapy and in combination with other oncology medicines. For example, it is part of the global phase 3 CELESTIAL-TNCLL study (NCT06073821), which is a fixed-duration trial combining sonrotoclax (a BCL2 inhibitor) with zanubrutinib (Brukinsa; a BTK inhibitor) to assess its superiority against a contemporary comparator, venetoclax (Venclexta) plus obinutuzumab (Gazvya).

This article was generated with assistance from Google Gemini and NotebookLM. It was edited and reviewed by Targeted Oncology staff. If you have any questions about the use of AI, please contact us.

REFERENCES:

1. BeOne Medicines Announces Positive Topline Results for Sonrotoclax in Relapsed or Refractory Mantle Cell Lymphoma (MCL). News release. BeOne Medicines. August 29, 2025. Accessed August 29, 2025. https://tinyurl.com/44uxu6b4

2. Study of BGB-11417 Monotherapy in Participants With Relapsed or Refractory Mantle Cell Lymphoma. ClinicalTrials.gov. Updated April 2, 2025. Accessed August 28, 2025. https://clinicaltrials.gov/study/NCT05471843