The FDA has approved zanubrutinib (Brukinsa®, BeiGene) for patients with relapsed/refractory mantle cell lymphoma (MCL) who have received at least one previous therapy.
The approval was based on two clinical trials. BGB-3111-206, a single-arm phase 2 trial, enrolled 86 patients with MCL whose disease progressed following at least one prior therapy. Patients received 160 mg of zanubrutinib orally twice daily until unacceptable toxicity or disease progression. The study's primary end point was overall response rate as assessed by an independent review committee. At a median follow-up of 36 weeks, zanubrutinib achieved an overall response rate of 84% and a complete response rate of 59%, with a median duration of response of 19.5 months.
BGB-3111-AU-003, a single-arm phase 1/2 trial, enrolled 32 patients with MCL whose disease progressed following at least one previous therapy. Patients received 160 mg of zanubrutinib administered orally twice daily or 320 mg administered once daily. Zanubrutinib achieved an overall response rate of 84% and a complete response rate of 22%; the median duration of response was 18.5 months.
The most common adverse events in both trials included upper respiratory tract infection, decreased white blood cell count, rash, bruising, diarrhea, cough, decreased hemoglobin, and decreased neutrophil, platelet, and white blood cell counts.
"Zanubrutinib was shown to be highly active in patients with relapsed/refractory MCL, as demonstrated by a high rate of complete response," conclude the authors of the BGB-3111-206 study, led by Yuqin Song, the Deputy Director of the Lymphoma Department at Peking University in China. "Zanubrutinib was generally well-tolerated, consistent with previous reports of zanubrutinib treatment in patients with various B-cell malignancies."
The recommended dose of zanubrutinib is 160 mg orally twice daily or 320 mg orally once daily.
For More Information
Song Y, Zhou K, Zou D, et al (2018). Safety and activity of the investigational bruton tyrosine kinase inhibitor zanubrutinib (BGB-3111) in patients with mantle cell lymphoma from a phase 2 trial. Blood, 132(suppl_1):148. DOI:10.1182/blood-2018-99-117956
Tam CS, Trotman J, Opat S, et al (2019). Phase 1 study of the selective BTK inhibitor zanubrutinib in B-cell malignancies and safety and efficacy evaluation in CLL. Blood, 134(11):851-859. DOI:10.1182/blood.2019001160
Image credit: Gabriel Caponetti. Licensed under CC BY-SA 3.0