The Food and Drug Administration has granted accelerated approval to lorlatinib for patients with anaplastic lymphoma kinase (ALK)–positive metastatic non–small cell lung cancer (NSCLC) whose disease has progressed on crizotinib and at least one other ALK inhibitor for metastatic disease or whose disease has progressed on alectinib or ceritinib as the first ALK inhibitor therapy for metastatic disease.
Approval of the next-generation ALK inhibitor was based on an overall response rate of 48% – with 4% complete and 44% partial – in a subgroup of 215 patients with ALK-positive metastatic NSCLC enrolled in a nonrandomized, phase 2 trial, the FDA said in a press announcement. All patients had been previously treated with one or more ALK kinase inhibitors.
The median response duration was 12.5 months (95% confidence interval, 8.4-23.7) and the intracranial overall response rate in 89 patients with measurable lesions in the CNS was 60% (95% CI, 49-70) with 21% complete and 38% partial responses.
Common adverse reactions in patients receiving lorlatinib were edema, peripheral neuropathy, cognitive effects, dyspnea, fatigue, weight gain, arthralgia, mood effects, and diarrhea. The most common laboratory abnormalities were hypercholesterolemia and hypertriglyceridemia, the FDA said.
The recommended dose of lorlatinib, to be marketed as Lorbrena by Pfizer, is 100 mg orally once daily.