FDA Grants Accelerated Approval to Zanubrutinib for R/R Follicular Lymphoma

The FDA has granted accelerated approval to zanubrutinib (Brukinsa) with obinutuzumab for the treatment of relapsed or refractory follicular lymphoma following 2 or more lines of systemic therapy.¹

This is the fifth oncology indication for zanubrutinib in the United States; it is the first and only FDA approved BTK inhibitor approved for follicular lymphoma.

A supplemental New Drug Application was accepted by the FDA in July 2023; zanubrutunib previously received Fast Track and Orphan Drug designations for this indication.²

The decision came after evaluation of data from the phase 2 ROSEWOOD clinical trial (Study BGB-3111-212; NCT03332017). In an earlier phase 1b study, investigators found that zanubrutinib plus obinutuzumab combination therapy was well-tolerated with an early efficacy signal. Building on those results, researchers for the open-label, multicenter, randomized phase 2 study sought to evaluate the efficacy and safety of combination zanubrutinib 160 mg twice daily plus obinutuzumab compared with obinutuzumab alone in this patient population.

The study cohort included 217 patients with relapsed/refractory follicular lymphoma who had received at least 2 previous lines of therapy; participants were randomly assigned in a 2:1 ratio to receive either zanubrutinib plus obinutuzumab or obinutuzumab alone. The primary endpoint of the study was overall response rate; secondary endpoints included duration of response, progression-free survival, overall survival, and safety. Study results were published last year in the Journal of Clinical Oncology.³

Study results met the primary endpoint, with an overall response rate of 69% for the combination therapy, vs 49% with obinutuzumab alone. Complete response rate, 18-month duration of response, and median progression-free survival were all higher in the combination therapy group (39% vs 19%, 69% vs 42%, and 28 months vs 10.4 months, respectively).

The most common adverse events noted by investigators in the combination therapy group included thrombocytopenia, neutropenia, diarrhea, and fatigue, with incidence rates of atrial fibrillation and major hemorrhage of 3% and 1%, respectively.

Across zanubrutinib clinical trial, the most common adverse reactions were decreased neutrophil and platelet counts (51%, 41%), upper respiratory tract infection (38%), hemorrhage (32%), and musculoskeletal pain (31%).¹

Recommended zaunburutinb dosing is 160 mg twice daily or 320 mg once daily until disease progression or unacceptable toxicity.

In addition to this new indication, zanubrutinib is approved to treat adult patients with chronic lymphocytic leukemia or small lymphocytic leukemia, Waldenoström macroglobulinemia, mantle cell lymphoma in patients who have received at least 1 prior line of therapy, and relapsed or refractory marginal zone lymphoma in adults who have received at least 1 anti-CD20-based treatment regimen.⁴

References

1. FDA grants accelerated approval to zanubrutinib for relapsed or refractory follicular lymphoma. FDA. March 7, 2024. Accessed March 7, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-zanubrutinib-relapsed-or-refractory-follicular-lymphoma

2. BeiGene announces FDA acceptance of sNDA for fifth Brukinsa indication. News release. BeiGene. July 12, 2023. Accessed March 7, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-zanubrutinib-relapsed-or-refractory-follicular-lymphoma

3. Zinzani PL, Mayer J, Flowers CR, et al. Rosewood: A phase II randomized study of zanubrutinib plus obinutuzumab versus obinutuzumab monotherapy in patients with relapsed or refractory follicular lymphoma. J Clin Oncol. 2023;41(33):5107-5177. Doi:10.1200/JCO.23.00775

4. FDA approves label update for Brukinsa (zanubrutinib) in chronic lymphocytic leukemia (CLL). News release. BeiGene. December 22, 2023. Accessed March 7, 2024. https://ir.beigene.com/news/fda-approves-label-update-for-brukinsa-zanubrutinib-in-chronic-lymphocytic-leukemia-cll/49b1ba2a-1f61-4034-9371-292f81d2ca57/