On March 7, the U.S. Food and Drug Administration (FDA) granted accelerated approval to the small-molecule BTK inhibitor zanubrutinib (Brukinsa) in combination with the anti-CD20 monoclonal antibody obinutuzumab for patients with relapsed or refractory follicular lymphoma after two or more lines of systemic therapy.
ROSEWOOD Study
The regimen was evaluated in Study BGB-3111-212 (ROSEWOOD; ClinicalTrials.gov identifier NCT03332017), an open-label, multicenter, randomized trial that enrolled 217 adult patients with relapsed or refractory follicular who had received at least two prior systemic treatments. Patients were randomly assigned 2:1 to receive either zanubrutinib at 160 mg orally twice daily until disease progression or unacceptable toxicity plus obinutuzumab or obinutuzumab alone. The median number of prior lines of therapy was three (range = 2–11).
Efficacy was based on overall response rate and duration of response as determined by an independent review committee. The overall response rate was 69% (95% confidence interval [CI] = 61%–76%) in the zanubrutinib plus obinutuzumab arm and 46% (95% CI = 34%–58%) in the obinutuzumab arm (two-sided P = .0012). With a median follow-up of 19.0 months, the median duration of response was not reached in the zanubrutinib plus obinutuzumab arm (95% CI = 25.3 months to not evaluable) and was 14.0 months (95% CI = 9.2–25.1 months) for patients receiving obinutuzumab monotherapy. The estimated duration of response rate at 18 months was 69% (95% CI = 58%–78%) in the zanubrutinib plus obinutuzumab arm.
Across clinical trials of zanubrutinib, the most commonly reported 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 follicular lymphoma who received zanubrutinib plus obinutuzumab.
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.
