On November 14, the U.S. Food and Drug Administration (FDA) granted accelerated approval to zanubrutinib (Brukinsa) for adult patients with mantle cell lymphoma who have received at least one prior therapy.
Richard Pazdur, MD
“Mantle cell lymphoma usually responds well to initial treatment, but eventually returns or stops responding, and the cancer cells continue to grow. This is a life-threatening condition,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence and Acting Director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research. “Clinical trials showed that 84% of patients saw tumor shrinkage with this therapy. For patients whose disease relapses or becomes refractory, secondary therapies may be successful in providing another remission, and today’s approval will provide patients with another treatment option.”
BGB-3111-206 and BGB-3111-AU-003
Efficacy was evaluated in BGB-3111-206, a phase II, open-label, multicenter, single-arm trial of 86 patients with mantle cell lymphoma who received at least one prior therapy. Oral zanubrutinib was given at 160 mg twice daily until disease progression or unacceptable toxicity. Efficacy was also assessed in BGB-3111-AU-003, a phase I/II, open-label, dose-escalation, global, multicenter, single-arm trial of B‑cell malignancies, including 32 patients with previously treated mantle cell lymphoma treated with zanubrutinib administered orally at 160 mg twice daily or 320 mg once daily.
The primary efficacy outcome measure in both trials was overall response rate (ORR) as assessed by an independent review committee. In trial BGB-3111-206, fluorodeoxyglucose (FDG)-positron emission tomography (PET) scans were required and the ORR was 84% (95% confidence interval = 74–91), with a complete response rate of 59% (95% CI = 48–70) and a median response duration of 19.5 months (95% CI = 16.6–not estimable). In trial BGB-3111-AU-003, FDG-PET scans were not required and the ORR was 84% (95% CI = 67–95), with a complete response rate of 22% (95% CI = 9–40) and a median response duration of 18.5 months (95% CI = 12.6–not estimable).
The most common adverse reactions (≥ 20%) included decreased neutrophil count, decreased platelet count, upper respiratory tract infection, decreased white blood cell count, decreased hemoglobin, rash, bruising, diarrhea, and cough. The most common serious adverse reactions were pneumonia in 11% and hemorrhage in 5% of patients.
The recommended zanubrutinib dose is 160 mg orally twice daily or 320 mg orally once daily.