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FDA Accepts sNDA for Zanubrutinib Plus Obinutuzumab for R/R Follicular Lymphoma


Following positive phase 2 results from the ROSEWOOD study, BeiGene is seeking FDA approval of zanubrutinib plus obinutuzumab for select patients with relapsed/refractory (R/R) follicular lymphoma.

A version of this article originally appeared on Targeted Oncology. This version has been lightly edited.

The FDA has accepted for review a supplemental new drug application (sNDA) for the combination of Zanubrutinib (Brukinsa) plus obinutuzumab (Gazyva) for the treatment of adult patients with relapsed or refractory (R/R) follicular lymphoma (FL) after at least 2 prior lines of therapy, according to BeiGene.1

Zanubrutinib is FDA approved to treat adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma, Waldenström macroglobulinemia, mantle cell lymphoma who have received at least 1 previous therapy, and R/R marginal zone lymphoma who have received 1 or more anti-CD20-based regimen. The combination was previously granted fast track and orphan drug designations for the treatment of R/R FL in adults.

Results from the phase 2 ROSEWOOD study (NCT03332017) support the sNDA. At a median follow-up of 12.5 months, the combination of zanubrutinib plus obinutuzumab generated superior efficacy compared with obinutuzumab alone with a 68.3% overall response rate (ORR) vs 45.8% respectively (P = .0017). The complete response (CR) rate was 37.2% vs 19.4% (P = .0083), respectively, and the 18-month landmark duration of response (DOR) was 69.3% for the combination.2 Overall, responses were durable.

Then, longer-term data showed that at a median follow-up of 20.2 months, the combination elicited an ORR of 69.0% vs 45.8% for obinutuzumab monotherapy (P = .0012), and the combination reduced the risk of disease progression or death by 50% vs obinutuzumab alone (HR, 0.50; 95% CI, 0.33-0.75).1

Further, safety results were consistent with previous studies of which evaluated both agents and the most common treatment-emergent adverse events (AEs) observed in the primary analysis for the combination arm compared with the obinutuzumab alone arm included diarrhea (18.2% v 16.9%), fatigue (15.4% v 14.1%), and pyrexia (13.3% v 19.7%).

“Follicular lymphoma is the most common slow-growing non-Hodgkin lymphoma, but there are limited treatment options for patients whose condition has progressed after two lines of therapy. We are therefore pleased that [zanubrutinib] is the first Bruton's tyrosine kinase inhibitor to demonstrate efficacy in follicular lymphoma and plan to continue worldwide regulatory submissions based on the ROSEWOOD results,” said Mehrdad Mobasher, MD, MPH, chief medical officer, Hematology, in the press release. “Importantly, we are grateful to the people living with relapsed or refractory follicular lymphoma who chose to participate in the ROSEWOOD study.”

Zanubrutinib is a small molecule inhibitor of Bruton’s tyrosine kinase (BTK) discovered being evaluated globally as a monotherapy and in combination with other therapies for the treatment of various B-cell malignancies. The agent is designed to deliver complete and sustained inhibition of the BTK protein throughout the optimization of bioavailability, half-life, and selectivity. Compared with other approved BTK inhibitors, zanubrutinib has shown to inhibit the proliferation of malignant B cells across multiple disease relevant tissues.

The target action date assigned by the FDA has been set for the first quarter of 2024, under the Prescription Drug User Fee Act.

The open-label, randomized, phase 2 ROSEWOOD study is evaluating the combination of zanubrutinib with obinutuzumab vs obinutuzumab monotherapy in patients with R/R FL who have received 2 or more lines of therapy.3 A total of 217 patients with pretreated R/R non-Hodgkin FL were enrolled in the study with 145 receiving the combination and 72 receiving obinutuzumab monotherapy.1

The primary end point is ORR assessed by independent central review (ICR) according to the Lugano classification, and secondary end points of the study include investigator-assessed ORR, DOR, progression-free survival, overall survival, and analysis of safety.


1. BeiGene Announces FDA acceptance of sNDA for fifth BRUKINSA indication. News release. BeiGene. July 12, 2023. Accessed July 12, 2023. https://tinyurl.com/4s2zr9fp

2. Zinzani PL, Mayer J, Auer R, et al. Zanubrutinib plus obinutuzumab (ZO) versus obinutuzumab (O) monotherapy in patients (pts) with relapsed or refractory (R/R) follicular lymphoma (FL): Primary analysis of the phase 2 randomized ROSEWOOD trial. J Clin Oncol. 2022;40(suppl 16): abstr 7510. doi: 10.1200/JCO.2022.40.16_suppl.7510

3. A study comparing obinutuzumab and BGB-3111 versus obinutuzumab alone in treating R/R follicular lymphoma (ROSEWOOD). ClinicalTrials.gov. Updated May 26, 2023. Accessed July 12, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT03332017

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