FDA Grants Accelerated Approval to Zanubrutinib for Marginal Zone Lymphoma

September 15, 2021

The following is a message from the Director of the FDA Oncology Center of Excellence, Dr. Richard Pazdur:

On September 14, 2021, the Food and Drug Administration granted accelerated approval to zanubrutinib (Brukinsa, BeiGene) for adult patients with relapsed or refractory marginal zone lymphoma (MZL) who have received at least one anti-CD20-based regimen.

Approval is based on two open-label, multicenter, single-arm trials: BGB-3111-214 (NCT03846427), which evaluated 66 patients with MZL who received at least one prior anti-CD20-based therapy, and BGB-3111-AU-003 (NCT02343120), which included 20 patients with previously treated MZL. Zanubrutinib was administered orally at 160 mg twice daily or 320 mg once daily.

The efficacy measures were overall response rate (ORR) and duration of response (DoR), as assessed by an independent review committee using the 2014 Lugano criteria. In the first trial, the CT-based ORR was 56% (95% CI: 43%, 68%), with 20% achieving complete responses (CR). In the second trial, the ORR was 80% (95% CI: 56%, 94%), with a CR rate of 20%. The median DoR was not estimable; the estimated 1-year rate of DoR was 85% (95% CI: 67, 93) and 72% (95% CI: 40, 88), respectively.

The most common adverse reactions (≥30%) to zanubrutinib include decreased neutrophil count, upper respiratory tract infection, decreased platelet count, hemorrhage, decreased lymphocyte count, rash, and musculoskeletal pain. Serious adverse reactions occurred in 40% of patients with MZL, most often from pyrexia and pneumonia. The prescribing information includes warnings and precautions for hemorrhage, infections, cytopenias, second primary malignancies, and cardiac arrythmias.

The recommended zanubrutinib dosage is 160 mg orally twice daily or 320 mg orally once daily until disease progression or unacceptable toxicity.

View full prescribing information for Brukinsa.

This indication is approved under accelerated approval based on ORR. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

This application was granted priority review, Fast Track Designation and Orphan 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.

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Please visit the FDA Hematology/Oncology (Cancer) Approvals & Safety Notifications webpage for a list of current and past approvals.