The FDA ( Food and Drug Administration ) has approved Alunbrig ( Brigatinib ) for adult patients with anaplastic lymphoma kinase ( ALK )-positive metastatic non-small cell lung cancer ( NSCLC ) as detected by an FDA-approved test.
The FDA has also approved the Vysis ALK Break Apart FISH Probe Kit as a companion diagnostic for Brigatinib.
Efficacy was investigated in ALTA 1L, a randomized ( 1:1 ), open-label, multicenter trial in 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 to receive Brigatinib 180 mg orally once daily with a 7-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 according to RECIST 1.1.
Additional efficacy outcome measures as evaluated by the BIRC was confirmed overall response rate ( ORR ).
Estimated median progression-free survival for patients treated with Brigatinib was 24 months ( 95% CI: 18.5, NE ) compared with 11 months ( 95% CI: 9.2, 12.9 ) for those treated with Crizotinib ( hazard ratio, HR 0.49; 95% CI: 0.35, 0.68; p less than 0.0001 ).
Confirmed ORR was 74% ( 95% CI: 66, 81 ) and 62% ( 95% CI: 53, 70 ), respectively.
The most common adverse reactions ( greater than or equal to 25% ) with Brigatinib 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 7 days; then increase to 180 mg orally once daily. Brigatinib may be taken with or without food. ( Xagena )
Source: FDA, 2020