Multicenter phase 3 trial of sacituzumab tirumotecan for EGFR-TKI-resistant, EGFR-mutated advanced NSCLC

Sacituzumab tirumotecan (sac-TMT) is and antibody-drug conjugate targeting TROP2. The multicenter phase 3 OptiTROP-Lung04 trial in China evaluated sac-TMT in patients with EGFR-mutated locally advanced or metastatic nonsquamous NSCLC that had progressed after EGFR-TKI therapy. Patients were randomized 1:1 to sac-TMT or pemetrexed plus platinum-based chemotherapy. Progression-free survival was significantly longer with sac-TMT than with chemotherapy (median, 8.3 months versus 4.3 months; HR 0.49; 95% CI 0.39-0.62). Overall survival was significantly longer with sac-TMT than with chemotherapy (after 18 months 65.8% versus 48.0%; HR 0.60; 95% CI 0.44-0.82). Treatment-related adverse events of grade 3 or higher occurred in 58.0% of patients in the sac-TMT group and 53.8% of patients in the chemotherapy group. The authors conclude that in patients with EGFR-mutated advanced or metastatic NSCLC that had progressed after previous EGFR-TKI therapy, survival outcomes were significantly better with sac-TMT than with platinum-based chemotherapy.