Zanubrutinib Plus Obinutuzumab Gets EU Approval for R/R Follicular Lymphoma

The European Commission has granted marketing authorization to the combination of zanubrutinib (Brukinsa) and obinutuzumab (Gazyva) for the treatment of adult patients with relapsed/refractory follicular lymphoma (FL) following at least 2 prior lines of systemic therapy.¹

The regulatory decision was based on findings from the phase 2 ROSEWOOD trial (NCT03332017). Findings demonstrated that the study met its primary end point; the overall response rate (ORR) by independent central review (ICR) was 69% (95% CI, 61%-76%), with a 39% complete response (CR) rate, vs 46% (95% CI, 34%-58%) and a 19% CR rate in the investigational and obinutuzumab monotherapy arms, respectively (2-sided P = .001). Moreover, the median duration of response (DOR) by ICR was not estimable (NE; 95% CI, 25.3-NE) vs 26.5 months (95% CI, 2.7-NE), respectively, the median progression-free survival (PFS) by ICR was 28.0 months (95% CI, 16.1-NE) vs 10.4 months (95% CI, 6.5-13.8), respectively (HR, 0.50; 95% CI, 0.33-0.75; P < .001), and the median overall survival (OS) was NE (95% CI, NE-NE) vs 34.6 months (95% CI, 29.3-NE), respectively (HR, 0.62; 95% CI, 0.35-1.07; P = .085).²

“With this approval, we are excited to announce that zanubrutinib will become available as a treatment option for patients with FL in the European Union,” Mehrdad Mobasher, MD, MPH, chief medical officer of hematology at BeiGene, said in a news release.¹ “Zanubrutinib is now the first BTK inhibitor approved in this indication and has the broadest label of any medicine in its class globally. This milestone marks a significant advancement in our efforts to combat the disease by providing a new and effective treatment option to patients who have either failed to respond to initial therapies or have experienced a relapse.”

The regulatory decision represents the fourth indication for zanubrutinib in the European Union. The agent is now approved for the treatment of more patient populations than any other BTK inhibitor in the European Union. Zanubrutinib is also approved as amonotherapy for the treatment of adult patients with chronic lymphocytic leukemia, for adult patients with marginal zone lymphoma who have received at least 1 prior anti-CD20-based treatment, and for adult patients with Waldenström’s macroglobulinemia who have received at least 1 prior therapy, or for the frontline treatment of patients unsuitable for chemoimmunotherapy.

The global, open-label ROSEWOOD trial randomly assigned patients with relapsed/refractory FL who were treated with at least 2 prior lines of systemic therapy, includingan anti-CD20 antibody and an alkylating agent, in a 2:1 manner to receive zanubrutinib plus obinutuzumab (n = 145) or obinutuzumab alone (n = 72). The primary end point was ORR by ICR, and secondary end points included DOR, PFS, OS, and safety.²

In terms of safety, the combination was found to be generally well tolerated with no new safety signals arising during ROSEWOOD. Patients in the zanubrutinib plus obinutuzumab safety population (n = 143) experienced any-grade treatment-emergent adverse effects (TEAEs) at a rate of 94% compared with 90% in the obinutuzumab arm (n = 71). The most common any-grade TEAEs in the combination arm were thrombocytopenia (36%), neutropenia (29%), and diarrhea (18%). Twelve patients in the zanubrutinib plus obinutuzumab arm experienced a TEAE leading to death compared with 7 in the obinutuzumab monotherapy arm.²

“People living with FL often experience relapse and have poor responses to subsequent lines of therapy, making it imperative to improve outcomes,” Pier Luigi Zinzani, MD, PhD, full professor of hematology at the Institute of Haematology Seràgnoli at the University of Bologna in Italy, said in the release.¹ “The results from the ROSEWOOD trial demonstrated a significant clinical benefit of zanubrutinib plus obinutuzumab for patients with relapsed or refractory follicular lymphoma. Zanubrutinib is a chemotherapy-free, oral treatment option that can be a practice-changing option for eligible patients with relapsed or refractory FL.”

In the United States, zanubrutinib has a submission under regulatory review by the FDA for the treatment of patients with relapsed/refractory FL.³ Submissions for zanubrutinib in relapsed/refractory FL are also under review in China, Canada, Switzerland, and the United Kingdom. The global development program of zanubrutinib has enrolled over 5000 patients in 29 countries and regions.¹

“We have made great progress in making zanubrutinib available to eligible patients with hematological malignancies globally, and this approval is a testament to our continued commitment to bring this much needed treatment option to patients in Europe and around the world,” Gerwin Winter, senior vice president and Head of Europe at BeiGene, said in the release. “We hope that this approval will have a positive impact on the lives of many people living with FL in the European Union and their families.”

References

1. BeiGene receives European Commission approval for Brukinsa (zanubrutinib) for the treatment of relapsed or refractory follicular lymphoma. News release. BeiGene. November 17, 2023. Accessed November 17, 2023. https://ir.beigene.com/news/beigene-receives-european-commission-approval-for-brukinsa-zanubrutinib-for-the-treatment-of-relapsed-or-refractory/cccb4985-af95-4002-9f1a-1ddd39eb3ca1/
2. 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):5107-5117. doi:10.1200/JCO.23.00775
3. BeiGene announces FDA acceptance of sNDA for fifth Brukinsa indication. News release. BeiGene. July 12, 2023. Accessed November 17, 2023. https://ir.beigene.com/news/beigene-announces-fda-acceptance-of-snda-for-fifth-brukinsa-indication/5e78f817-3655-4679-ab15-45715fddf585/