FDA Grants Accelerated Approval to Brigatinib for Metastatic NSCLC
The most common serious adverse events were pneumonia and interstitial lung disease (ILD)/pneumonitis.
The Food and Drug Administration (FDA) has granted accelerated approval to Alunbrig (brigatinib; ARIAD) tablets for the treatment of metastatic anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) in patients who have progressed or are intolerant to crizotinib.
The accelerated approval was based on data from the ALTA trial, a non-comparative, 2-arm, open-label, multicenter clinical trial showing a clinically meaningful and durable overall response rate (ORR) in patients with locally advanced or metastatic ALK-positive NSCLC who progressed on crizotinib. Study patients were randomized to oral brigatinib 90mg daily (n=112) or brigatinib 180mg daily (n=110) after a 7-day lead-in of 90mg daily.
ORR in the 90mg arm was 48% (95% CI: 39%, 58%) and was 53% (95% CI: 43%, 62%) in the 180mg arm. The median duration of responses (DOR) was 13.8 months in both treatment arms.
Among patients with measurable brain metastases data, intracranial ORR was 42% (95% IC: 23%, 63%) in the 90mg arm and 67% (95% CI: 41%, 87%) in the 180mg arm. The median intracranial DOR was 5.6 months in the 180mg arm; it was not calculable in the 90mg arm. Moreover, 78% and 68% of patients in the 90mg and 180mg arms who had an intracranial response, respectively, maintained this response for ≥4 months.
The most common adverse events (occurring ≥25%) were nausea, diarrhea, fatigue, cough, and headache. The most common serious adverse events were pneumonia and interstitial lung disease (ILD)/pneumonitis.
Brigatinib is an investigational oral anaplastic lymphoma kinase (ALK) inhibitor that has activity at clinically achievable concentrations against multiple kinases including ALK, ROS1, insulin-like growth factor-1 receptor (IGF-1R), and FLT-3 as well as EGFR deletion and point mutations. Brigatinib exhibited in vivo anti-tumor activity against four mutant forms of EML4-ALK, including G1202R and L1196M mutants identified in NSCLC tumors in patients who have progressed on crizotinib.
Alunbrig will be available as 30mg strength tablets in 21- and 180-count bottles and as 90mg strength tablets in 7- and 30-count bottles.
Takeda announces FDA accelerated approval of ALUNBRIG™ (brigatinib) [press release]. Cambridge, MA: Ariad. Published April 28, 2017. Accessed on May 4, 2017.