Sonrotoclax Approval Delivers a Long-Awaited New Option for Relapsed or Refractory Mantle Cell Lymphoma

The FDA approved sonrotoclax (Beqalzi; BeOne Medicines) for the treatment of adult patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL), after at least 2 lines of systemic therapy, including a Bruton tyrosine kinase (BTK) inhibitor. The decision makes sonrotoclax the first B-cell lymphoma 2 (BCL2) inhibitor indicated for R/R MCL.¹

What is Sonrotoclax?

Sonrotoclax is a foundational, next-generation BCL2 inhibitor with a unique pharmacokinetic and pharmacodynamic profile. According to the news release announcing its approval, sonrotoclax was proven in preclinical and clinical studies to be a highly potent and specific BCL2 inhibitor with a short half-life and no drug accumulation. Additionally, it demonstrated promising clinical activity across a range of B-cell malignancies, including chronic lymphocytic leukemia (CLL), and is currently in development as a monotherapy and part of combination regimens, including one with zanubrutinib (Brukinsa; BeiGene).¹

“This indication is approved under accelerated approval based on response rate and duration of response, and continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials,” stated the news release.¹

“For people living with R/R MCL, each progression can bring uncertainty and questions regarding remaining treatment options. The FDA approval of sonrotoclax represents significant progress for the US MCL community, offering renewed hope for patients and families who have exhausted other available therapies. Advances like this underscore why continued research and innovation in this disease remain so critical,” Meghan Gutierrez, CEO of the Lymphoma Research Foundation, said in the news release.¹

What Clinical Data Supported Sonrotoclax’s Approval?

The accelerated approval of sonrotoclax is supported by efficacy and safety data from the BGB-11417-201 (NCT05471843)² study, a single-arm, open-label, multicenter, dose-escalation/expansion phase 1/2 clinical trial evaluating the efficacy, safety, and pharmacokinetics of sonrotoclax in patients with R/R MCL. Patients received either 160 mg (n = 10) or 230 mg (part 1: n = 12; part 2: n = 103) of sonrotoclax.²

In the part 1 dose-escalation and safety expansion, sonrotoclax was orally administered once daily with a ramp-up to the target doses of 160 mg and 320 mg. The part 2 efficacy expansion used sonrotoclax at the recommended phase 2 dose (RP2D) and implemented a simplified ramp-up schedule.^2,3

The trial’s primary end points were dose-limiting toxicities (DLTs), treatment-emergent adverse events (TEAEs), and tumor lysis syndrome (TLS) for part 1, and independent review committee (IRC)-assessed overall response rate (ORR)—partial response or better—for part 2. The findings were presented at the 2025 American Society of Hematology (ASH) Annual Meeting & Exposition and were published in Blood.^1-3

According to findings published in Blood, there were no observed DLTs in part 1 of the trial. Sonrotoclax 320 mg was chosen as the RP2D based on safety and efficacy evaluation.^2,3

The median study follow-up was about 10.1 months (range, 0.1–23.3 months). At the data cutoff date, approximately 31.3% of patients (n = 36) remained on treatment. In 103 efficacy-evaluable patients of part 2 in the 320-mg group, the ORR by IRC was approximately 53.4% (n = 55; ORR by INV, 48.5% [n = 50]) and the complete response (CR) rate by IRC was 14.6% (n = 15; CR rate by INV, 17.5% [n = 18]).

Additionally, median time to response by both IRC and INV was 1.9 months (range, 1.6-6.5 months), and median duration of response (DOR) was 15.8 months for both IRC (95% CI, 7.2 months–NE) and INV (95% CI, 7.4 months–NE) with median follow-ups of 7.4 and 9.3 months, respectively. The median progression-free survival was 6.5 months by IRC (95% CI, 4.0–9.1 months) and 6.3 months by INV (95% CI, 3.7–9.1 months). Median overall survival was not reached, according to the study authors.³

The most common grade 3 or higher TEAE was neutropenia (19.1%). Overall, approximately 36.5% of patients (n = 42) had a serious TEAE, of which the most common was pneumonia (7.0%). Only 16 patients (13.9%) discontinued treatment due to TEAEs and death occurred in 15 patients (13.0%). There were 42 deaths (36.5%), of which most were due to disease progression (n = 29) and not necessarily the treatment itself. Additionally, clinical TLS occurred in 2 patients (1.7%) and laboratory TLS in 6 (5.2%). All recovered without sequelae.³

“The data supporting the approval of sonrotoclax in the US confirm its role as a foundational therapy for mantle cell lymphoma in the post-BTK inhibitor setting and demonstrate that it can deliver robust disease control when treatment choices are limited and outcomes are poor,” said Michael Wang, MD, global principal investigator, the Puddin Clarke Endowed Professor, Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center. “From a clinical perspective, this provides physicians with an important new option grounded in both efficacy and tolerability, fundamentally changing how we think about sequencing therapy in this disease.”¹

REFERENCES

1. BeOne Medicines’ BEQALZI™ (sonrotoclax) Approved by U.S. FDA as First and Only BCL2 Inhibitor for R/R Mantle Cell Lymphoma. Businesswire. News release. May 13, 2026. Accessed May 13, 2026. https://www.businesswire.com/news/home/20260513542161/en/BeOne-Medicines-BEQALZI-sonrotoclax-Approved-by-U.S.-FDA-as-First-and-Only-BCL2-Inhibitor-for-RR-Mantle-Cell-Lymphoma

2. Study of BGB-11417 Monotherapy in Participants With Relapsed or Refractory Mantle Cell Lymphoma. ClinicalTrials.gov identifier: NCT05471843. Updated September 9, 2025. Accessed May 13, 2026. https://clinicaltrials.gov/study/NCT05471843

3. 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(Supplement 1):663. doi:10.1182/blood-2025-663