FDA gives accelerated approval to Lorbrena for ALK-positive metastatic non-small cell lung cancer.- Pfizer.

Pfizer announced that the FDA has approved Lorbrena (lorlatinib), a third-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) for patients with 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. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

The approval was based on a non-randomized, dose-ranging and activity-estimating, multi-cohort, multicenter Phase I/II study, B7461001, evaluating Lorbrena for the treatment of patients with ALK-positive metastatic NSCLC, who were previously treated with one or more ALK TKIs. A total of 215 patients with ALK-positive metastatic NSCLC were enrolled across various subgroups based on prior treatment. Among these patients, overall response rate (ORR) was 48 percent (95% CI: 42%, 55%) and importantly, 57 percent had previous treatment with more than one ALK TKI. In the trial, 69 percent of patients had a history of brain metastases and intracranial response rate was 60 percent (95% CI: 49%, 70%). Among 295 ALK-positive or ROS1-positive metastatic NSCLC patients who received Lorbrena 100 mg once daily in study B7461001, the most common (at least 20%) adverse reactions were edema, peripheral neuropathy, cognitive effects, dyspnea, fatigue, weight gain, arthralgia, mood effects, and diarrhea.