Lorlatinib in patients with ALK-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 (ALK)-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 ALK-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 (n = 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 ALK-positive metastatic NSCLC.

CLINICAL TRIAL REGISTRATION: clinicaltrials.gov identifier is NCT04362072.