Updated Efficacy and Safety of Lorlatinib in a Phase 2 Study in Chinese Patients With Previously Treated Advanced ALK-Positive Nonsmall Cell Lung Cancer

Abstract

ObjectivesLorlatinib, a brain-penetrant, third-generation anaplastic lymphoma kinase (ALK) inhibitor, demonstrated robust overall and intracranial antitumor activity in patients with advanced ALK-positive nonsmall cell lung cancer (NSCLC) previously treated with an ALK inhibitor in a global phase 1/2 study (NCT01970865) and a multicenter phase 2 study conducted in China (NCT03909971). Here, we report updated 3-year follow-up data from the phase 2 study in China. Materials and MethodsChinese patients with locally advanced or metastatic ALK-positive NSCLC who had disease progression after crizotinib as the only prior ALK inhibitor (cohort 1) or after 1 ALK inhibitor other than crizotinib, with or without prior crizotinib (cohort 2), were enrolled in the study. All patients received lorlatinib 100 mg once daily. ResultsOverall, 109 patients were enrolled (67 in cohort 1 and 42 in cohort 2). At data cutoff (September 30, 2022), the median duration of follow-up for progression-free survival (PFS) was 35.8 months in cohort 1 and 33.1 months in cohort 2. Median PFS (95% CI) per independent central review was 26.3 months (16.6-35.9) in cohort 1 and 5.6 months (2.9-12.4) in cohort 2. The median duration of follow-up for overall survival (OS) was 36.4 months in cohort 1 and 37.5 months in cohort 2. Median OS (95% CI) was not reached (NR; NR-NR) in cohort 1 and 21.9 months (11.9-NR) in cohort 2. Median intracranial time to tumor progression (95% CI) was NR (NR-NR) in cohort 1 and NR (9.7 months-NR) in cohort 2. No new safety signals emerged with long-term treatment. ConclusionWith approximately 2 years of additional follow-up since the prior analysis, the long-term data confirm robust overall and intracranial clinical activity of lorlatinib, with no new safety signals emerging. These results support the use of lorlatinib in Chinese patients with previously treated ALK-positive NSCLC with or without brain metastases.ClinicalTrials.gov NCT03909971.