BeOne Medicines announced on November 3, 2026, that the U.S. Food and Drug Administration (FDA) has accepted and granted Priority Review to a supplemental new drug application (sNDA) for zanubrutinib (BRUKINSA) in combination with rituximab for the treatment of adult patients with previously untreated mantle cell lymphoma (MCL). If approved, the regimen would represent the first chemotherapy-free, BTK inhibitor-based option in the frontline MCL setting.
The application is supported by data from the pivotal Phase 3 MANGROVE trial, in which zanubrutinib plus rituximab reduced the risk of disease progression or death by 43% compared with bendamustine plus rituximab (HR=0.57; 95% CI, 0.43–0.76; p<0.0001). Full trial results have not yet been published and are scheduled to be presented during the Plenary Scientific Session at the 68th American Society of Hematology (ASH) Annual Meeting on December 13, 2026.
Key finding
In the Phase 3 MANGROVE trial, zanubrutinib plus rituximab reduced the risk of progression or death by 43% versus bendamustine plus rituximab in previously untreated MCL (HR=0.57; p<0.0001); however, full results — including response rates, duration of response, and overall survival data — have not yet been publicly reported and are pending presentation at ASH 2026.
Study Design
| Trial | MANGROVE (BGB-3111-306); global, randomized, open-label Phase 3 |
|---|---|
| Population | Adult patients with previously untreated mantle cell lymphoma; 510 patients enrolled across 157 sites worldwide |
| Treatment | Experimental arm: zanubrutinib 160 mg orally twice daily plus rituximab, followed by zanubrutinib monotherapy until progression or intolerance; Control arm: bendamustine plus rituximab for six cycles |
| Primary endpoint | Progression-free survival (PFS) as assessed by independent review committee (IRC) |
| Key secondary endpoints | Overall survival (OS), investigator-assessed PFS, overall response rate (ORR), duration of response (DOR), patient-reported outcomes, and safety |
MANGROVE is a global phase 3 trial comparing chemotherapy-free zanubrutinib plus rituximab with bendamustine plus rituximab in patients with previously untreated MCL who are ineligible for stem cell transplantation. The scale of the trial — 510 patients across 157 global sites — positions it as a potentially practice-defining dataset for newly diagnosed MCL, a disease in which chemoimmunotherapy has remained the standard of care despite its associated toxicity burden.
Results and Safety
Zanubrutinib plus rituximab met the trial’s primary endpoint of IRC-assessed PFS, reducing the risk of progression or death by 43% versus bendamustine plus rituximab (HR=0.57; 95% CI, 0.43–0.76; p<0.0001). These topline efficacy data formed the basis of the sNDA submission accepted by the FDA.
Numerical response rates, duration of response, patient-reported outcome results, and overall survival data were not disclosed in the announcement. Those findings, along with the complete dataset, are expected to be presented at the ASH Annual Meeting on December 13, 2026.
BeOne Medicines reported that the safety profile of zanubrutinib plus rituximab was consistent with the known profiles of each individual agent, and that no new safety signals were identified. No further safety detail was provided in the announcement.
Clinical Context
Mantle cell lymphoma is an aggressive B-cell malignancy for which frontline chemoimmunotherapy — typically bendamustine plus rituximab or intensive cytarabine-based regimens — has long been the standard of care. While BTK inhibitors, including zanubrutinib, are already approved in the relapsed or refractory MCL setting, no chemotherapy-free BTK inhibitor-based regimen has previously been approved for first-line use. A positive FDA decision would expand zanubrutinib’s existing U.S. label, which currently covers relapsed or refractory MCL alongside several other B-cell malignancies.
Regulatory submissions have also been submitted in Europe and accepted in China, suggesting a broad international development strategy. The FDA’s Priority Review designation indicates the agency has determined the application may offer a significant improvement over available therapy, though it does not guarantee approval. The PDUFA target action date was not disclosed in the announcement, and the clinical implications of the overall survival data — a key secondary endpoint — remain unknown pending full presentation of the trial results.
Sources
- BeOne Medicines Ltd. via Business Wire. “U.S. FDA Grants Priority Review to BeOne Medicines’ BRUKINSA Combination in First-Line Mantle Cell Lymphoma.” Press release. November 3, 2026. View source.
