The following is a message from the Director of the FDA Oncology Center of Excellence, Dr. Richard Pazdur:
On March 7, 2024, the Food and Drug Administration granted accelerated approval to zanubrutinib (Brukinsa, BeiGene USA, Inc.) with obinutuzumab for relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy.
Full prescribing information for Brukinsa will be posted here.
The regimen was evaluated in Study BGB-3111-212 (ROSEWOOD; NCT03332017), an open-label, multicenter, randomized trial that enrolled 217 adult patients with relapsed or refractory FL after at least 2 prior systemic treatments. Patients were randomized (2:1) to receive either zanubrutinib 160 mg orally twice daily until disease progression or unacceptable toxicity plus obinutuzumab (ZO), or obinutuzumab alone. The median number of prior lines of therapy was 3 (range 2-11).
Efficacy was based on overall response rate (ORR) and duration of response (DOR) determined by an independent review committee. ORR was 69% (95% CI: 61, 76) in the ZO arm and 46% (95% CI: 34, 58) in the obinutuzumab arm (two-sided p-value, 0.0012). With a median follow-up of 19.0 months, the median DOR was not reached in the ZO arm (95% CI: 25.3 months, NE) and was 14.0 months (95% CI: 9.2, 25.1) for those patients receiving obinutuzumab monotherapy. The estimated DOR rate at 18 months was 69% (95% CI: 58, 78) in the ZO arm.
Across clinical trials of zanubrutinib, the most common adverse reactions (≥30%), including laboratory abnormalities, were decreased neutrophil counts (51%) and platelet counts (41%), upper respiratory tract infection (38%), hemorrhage (32%), and musculoskeletal pain (31%). Serious adverse reactions occurred in 35% of patients with FL who received ZO.
The recommended zanubrutinib dosage is 160 mg taken orally twice daily or 320 mg taken orally once daily until disease progression or unacceptable toxicity.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
This application was granted fast track designation and orphan drug designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.
For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.
Follow the Oncology Center of Excellence on X (formerly Twitter) @FDAOncology.
