Lorlatinib in patients with -positive metastatic NSCLC previously treated with an ALK inhibitor: results from a phase IV study.

[AIMS] This post-approval study was conducted to confirm efficacy of lorlatinib in anaplastic lymphoma kinase ()-positive metastatic non-small cell lung cancer (NSCLC) that progressed on one prior second-generation ALK tyrosine kinase inhibitor.

[PATIENTS & METHODS] In this phase IV open-label study, patients with -positive metastatic NSCLC that progressed on first-line alectinib or ceritinib received lorlatinib 100 mg once daily. Primary endpoint was objective response rate (ORR) per RECIST 1.1 by independent central review (ICR).

[RESULTS] Among 71 patients treated with lorlatinib, 85% had received prior alectinib and 15% received prior ceritinib. Median duration of lorlatinib treatment was 9.7 months. ORR was 42% (95% CI, 31%-55%); median duration of response was not reached. Median progression-free survival was 12.2 months (95% CI, 6.9-22.1). In patients with central nervous system metastases ( = 30), intracranial ORR was 47%. Any-grade treatment-emergent adverse events (TEAEs) occurred in 97% of patients; grade ≥3 occurred in 39%. TEAEs led to dose interruption in 31% and dose reduction in 15% of patients; none discontinued due to treatment-related adverse events.

[CONCLUSIONS] These phase IV efficacy and safety results remained consistent with the pivotal phase I/II study. Lorlatinib continued to show clinically meaningful benefit in patients with previously treated -positive metastatic NSCLC.

[CLINICAL TRIAL REGISTRATION] clinicaltrials.gov identifier is NCT04362072.