FDA Grants Accelerated Approval to Zanubrutinib for Mantle Cell Lymphoma

November 14, 2019

From the American Society of Clinical Oncology in cooperation with the Food and Drug Administration (FDA) and as a service to our members, ASCO will periodically distribute information about newly approved therapies for cancer patients. This helps FDA inform oncologists and professionals in oncology-related fields about recent approvals in a timely manner. Included in the email from the FDA will be a link to the product label, which will provide the relevant clinical information on the indication, contraindications, dosing, and safety. In sending this information, ASCO does not endorse any product or therapy and does not take any position on the safety or efficacy of the product or therapy described. The following is a message from the Director of the FDA Oncology Center of Excellence, Dr. Richard Pazdur:

On November 14, 2019, the Food and Drug Administration granted accelerated approval to zanubrutinib (BRUKINSA™, BeiGene, Ltd.) for adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.

Efficacy was evaluated in BGB-3111-206 (NCT03206970), a phase 2 open-label, multicenter, single-arm trial of 86 patients with MCL who received at least one prior therapy. Zanubrutinib was given orally at 160 mg twice daily until disease progression or unacceptable toxicity. Efficacy was also assessed in BGB-3111-AU-003 (NCT 02343120), a phase 1/2, open-label, dose-escalation, global, multicenter, single-arm trial of B‑cell malignancies, including 32 previously treated MCL patients 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, FDG-PET scans were required and the ORR was 84% (95% CI: 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.

View full prescribing information for BRUKINSA.

FDA granted this application priority review and zanubrutinib received orphan product and breakthrough therapy designations for treatment of MCL. 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 Twitter @FDAOncology.


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