Lung Cancer Drug Alunbrig Wins FDA Nod as Second-Line Treatment

Accelerated approval based on mid-stage response rate

Brigatinib (Alunbrig, Takeda Pharmaceutical Company) has received accelerated approval from the FDA for the treatment of patients with anaplastic lymphoma kinase-positive (ALK+) metastatic non–small-cell lung cancer (NSCLC) who have progressed on or are intolerant of crizotinib. The accelerated approval was based on the overall response rate (ORR) and the duration of response (DOR) in a phase 2 study. Continued approval for this indication may be contingent on the verification of clinical benefit in a confirmatory trial.

Brigatinib, which previously received a breakthrough therapy designation from the FDA, is a once-daily oral therapy that may be taken with or without food. It was discovered by Ariad Pharmaceuticals, which was acquired by Takeda in February 2017.

The recommended dosing regimen is 90 mg once daily for the first seven days. If 90 mg is tolerated during this period, the dosage is increased to 180 mg once daily.

The ongoing phase 2, open-label ALK in Lung Cancer Trial of AP26113 (ALTA) enrolled 222 adults with locally advanced or metastatic ALK+ NSCLC who had progressed during treatment with crizotinib. The patients received either 90 mg of brigatinib once daily (n =112) or 180 mg once daily (n = 110) after a seven-day lead-in of 90 mg once daily. The primary efficacy endpoint was the confirmed ORR, according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1). Additional efficacy outcome measures included investigator-assessed ORR, intracranial ORR, DOR, and intracranial DOR.

With a median follow-up period of 8.0 months (range, 0.1 months to 20.2 months), the results demonstrated a confirmed ORR of 53% (as assessed by an independent review committee [IRC]) or 54% (as assessed by the investigator) among the patients who received the recommended brigatinib dosing regimen of 90 mg once daily, increased to 180 mg once daily. In this group, the median duration of response was 13.8 months by IRC assessment or 11.1 months by investigator assessment.

Among the 23 patients who exhibited an intracranial response, 78% of the 90-mg arm and 68% of the 180-mg arm maintained that response for at least four months.

The warnings and precautions for brigatinib include interstitial lung disease/pneumonitis, hypertension, bradycardia, visual disturbance, creatine phosphokinase (CPK) elevation, pancreatic enzyme elevation, hyperglycemia, and embryo-fetal toxicity.

At the recommended dosing regimen, the most common adverse events associated with brigatinib included nausea, diarrhea, fatigue, cough, and headache.

Source: Takeda; April 28, 2017.