Zanubrutinib/Obinutuzumab sNDA Is Accepted by FDA for R/R Follicular Lymphoma

The FDA has accepted a supplemental new drug application zanubrutinib (Brukinsa) plus obinutuzumab (Gazyva) for the treatment of adult patients with relapsed/refractory follicular lymphoma following 2 previous lines of treatment, according to a press release from developer BeiGene.¹

The regulatory decision follows news of the combination’s orphan drug designation in the same indication. A Prescription Drug User Fee Act date has been set by the FDA for the first quarter of 2024.

The application is supported by data from the phase 2 ROSEWOOD trial (NCT03332017) in which a total of 217 patients with previously treated, relapsed/refractory non-Hodgkin follicular lymphoma were treated with the aforementioned combination regimen or obinutuzumab alone.

The application is supported by data from the phase 2 ROSEWOOD trial (NCT03332017) in which a total of 217 patients with previously treated, relapsed/refractory non-Hodgkin follicular lymphoma were treated with the aforementioned combination regimen (n = 145) or obinutuzumab alone (n = 72).² Study findings indicated that with a median follow-up of 12.5 months, the overall response rate (ORR) with zanubrutinib/obinutuzumab was 68.3% compared with 45.8% in the obinutuzumab alone cohort (P = .0017).

According to the study readout from 2022, the 18-month duration of response (DOR) was 70.9% in the combination arm compared with 54.6% in the monotherapy arm.

Common any-grade adverse effects (AEs) in the combination arm included thrombocytopenia (34.3%), neutropenia (27.3%), diarrhea (16.1%), fatigue (14.0%), constipation (13.3%), cough (11.9%), pyrexia (11.2%), and dyspnea (10.5%). In terms of high-grade AEs, investigators reported neutropenia (22.4%) and thrombocytopenia (14.0%). A total of 5.6% of those in the combination arm and 9.9% in the single-agent arm experienced treatment-emergent adverse effects that led to death.

“Follicular lymphoma is the most common slow-growing non-Hodgkin lymphoma, but there are limited treatment options for patients whose condition has progressed after 2 lines of therapy,” Mehrdad Mobasher, MD, MPH, chief medical officer of Hematology, at BeiGene, said in the press release. “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.”

Patients who enrolled on the ROSEWOOD study received oral zanubrutinib as two 80 mg capsules twice daily followed by 1000 mg of intravenous obinutuzumab on days 1, 8, and 15 of cycle 1; day 1 of cycles 2 to 6; and every 8 weeks thereafter. Those in the control group received the same obinutuzumab backbone.

The study’s primary end point was ORR, with secondary end points including DOR, progression-free survival, overall survival, complete response rate, health-related quality of life, and safety and tolerability.

To enroll on the study, patients were required to have histologically confirmed B-cell follicular lymphoma that had been treated with at least 2 previous systemic therapies. Patients also needed to have experienced disease progression following the completion of their most recent treatment or refractory disease, as well as having measurable disease. Archival tissue for diagnosis confirmation, an ECOG performance status of 0 to 2, and adequate renal and hepatic function are also necessary for trial enrollment.

Single-agent zanubrutinib previously received accelerated approval for the treatment of relapsed/refractory marginal zone lymphoma (MZL) after at least 1 previous anti–CD20-based regimen in September 2021.³ This decision was based on data from the phase 2 MAGNOLIA study (NCT03846427), in which patients with relapsed/refractory MZL experienced a high rate of response following treatment with the agent.

References

1. BeiGene Announces FDA Acceptance of sNDA for Fifth BRUKINSA® Indication. News release. BeiGene. July 12, 2023. Accessed July 12, 2023. https://bit.ly/3XMhdQ6
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): 7510. doi:10.1200/JCO.2022.40.16_suppl.7510
3. U.S. FDA Grants BRUKINSA® (Zanubrutinib) Accelerated Approval in Relapsed or Refractory Marginal Zone Lymphoma. News release. BeiGene, Ltd. September 15, 2021. Accessed July 12, 2023. https://bit.ly/3EjrngK