Management Strategy of 1L Lorlatinib With Hyperlipidemia in Stage IIIB-IV ALK Positive NSCLC

Lorlatinib, a third-generation ALK-TKI, has demonstrated remarkable efficacy as first-line treatment for ALK-positive advanced NSCLC, with a 5-year PFS rate of 60% in the CROWN study. However, hyperlipidemia is the most common adverse event - hypercholesterolemia occurs in 72% and hypertriglyceridemia in 66% of patients. Despite this, no standardized lipid management guidelines exist specifically for the lorlatinib treatment context. This study addresses this gap through a dual-part design conducted across 8 sites in China. Part A documents real-world hyperlipidemia management patterns in routine clinical practice. Part B is a randomized controlled trial comparing intensive versus standard lipid-lowering strategies in patients with high-risk factors who develop hyperlipidemia on first-line lorlatinib. To address ethical review feedback, the protocol was revised from V1.1 (Dec 15, 2025) to V1.2 (Apr 7, 2026), with revisions including correcting the reversal of primary endpoints between Part A and Part B, expanding inclusion/exclusion criteria in the synopsis, removing "tissue donation" language from the ICF, and refining FMD testing requirements. Patient follow-up extends up to 60 months post-enrollment for survival data.