Lorlatinib Plus Sacituzumab Tirumotecan With Peripheral ctDNA Guidance as First-Line Therapy for ALK Fusion-Positive NSCLC

All enrolled subjects are patients with locally advanced or metastatic ALK fusion NSCLC who are not candidates for curative therapy. This study plans to enroll approximately 153 eligible subjects, who will be stratified into a ctDNA-positive group and a ctDNA-negative group based on baseline peripheral blood ctDNA status. Subjects in the ctDNA-negative group will receive lorlatinib monotherapy. Subjects in the ctDNA-positive group will be randomized in a 1:1 ratio to receive either lorlatinib combined with sacituzumab tirumotecan or lorlatinib monotherapy. Each treatment cycle consists of 4 weeks (28 days). Subjects receiving lorlatinib monotherapy will receive lorlatinib 100 mg orally once daily (QD). Subjects receiving the combination therapy will receive lorlatinib 100 mg orally once daily (QD) plus sacituzumab tirumotecan 4 mg/kg administered as an intravenous infusion on Day 1 and Day 15 of each 4-week cycle (Q4W) for 4 cycles.