On May 22, 2020, the U.S. Food and Drug Administration (FDA) approved brigatinib (Alunbrig®) for adult patients with anaplastic lymphoma kinase (ALK)-positive, metastatic non-small cell lung cancer (NSCLC). FDA also approved the Vysis ALK Break Apart FISH Probe Kit as a companion diagnostic for brigatinib. 

FDA Approves Brigatinib for ALK-Positive, Metastatic NSCLC

Efficacy was investigated in a randomized, open-label, multicenter trial (ALTA 1L; NCT02737501) of adult patients with advanced ALK-positive NSCLC who had not previously received an ALK-targeted therapy. The trial required patients to have an ALK rearrangement based on a local standard of care testing. The trial randomized 275 patients 1:1 to receive brigatinib 180 mg orally once daily with a seven-day lead-in at 90 mg once daily (n = 137) or crizotinib 250 mg orally twice daily (n = 138). A subset of the clinical samples was retrospectively tested with the Vysis ALK Break Apart FISH Probe Kit. Of the enrolled patients, 239 had positive results using the Vysis diagnostic test. Central results were negative for 20 patients and unavailable for 16 patients. 

The major efficacy outcome measure was progression-free survival (PFS) evaluated by a blinded independent review committee (BIRC) according to response evaluation criteria in solid tumors 1.1. An additional efficacy outcome measure, as evaluated by the BIRC, was confirmed overall response rate (ORR). 

Estimated median PFS for patients treated with brigatinib was 24 months (95% CI = 18.5, not evaluated) compared to 11 months (95% CI = 9.2, 12.9) for those treated with crizotinib (HR = 0.49; 95% CI = 0.35, 0.68; p < 0.0001). Confirmed ORR was 74% (95% CI = 66, 81) and 62% (95% CI = 53, 70), respectively.  

The most common adverse reactions (≥ 25%) were diarrhea, fatigue, nausea, rash, cough, myalgia, headache, hypertension, vomiting, and dyspnea. 

The recommended brigatinib dose is 90 mg orally once daily for the first seven days, then increased to 180 mg orally once daily. Brigatinib may be taken with or without food. 

View full prescribing information for brigatinib

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

FDA granted the application priority review. Brigatinib also received orphan drug 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 800-FDA-1088.   

For assistance with single-patient oncology investigational new drug applications, contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.