Lorviqua® (lorlatinib) is reimbursed for the treatment of patients with ALK-positive advanced non-small cell carcinoma who progressed during or after prior therapy with a second-generation ALK tyrosine kinase inhibitor (TKI). The use of lorlatinib in the treatment of ALK-positive advanced NSCLC after treatment with at least one second-generation ALK TKI was investigated in a single-arm, multicentre phase I/II study enrolling 139 patients. Patients received lorlatinib orally at the recommended dose of 100 mg once daily, continuously. The primary efficacy endpoint in the phase II portion of the study was objective response rate (ORR), including intracranial (IC)-ORR, as per Independent Central Review (ICR) according to modified response evaluation criteria in solid tumours (modified RECIST version 1.1). In the overall efficacy population of 139 patients, 56 patients (40.3%) had a confirmed objective response by ICR. The ORR was 42.9% (95% confidence interval [CI] 24.5-62.8) in the 28 patients who received one prior ALK TKI and 39.6% (95% CI 30.5- 49.4) in the 111 patients who received ≥2 prior ALK TKI. Median progression-free survival (PFS) was 5.5 months (95% CI 2.9-8.2) and 6.9 months (95% CI 5.4-9.5), respectively. The IC-ORR was 66.7% (95% CI 29.9-92.5) in patients who received one prior ALK TKI and 52.1% (95% CI 37.2-66.7) in patients who received ≥2 prior ALK TKI.