Sac-TMT Shows Significant Survival Benefit in Pretreated EGFR-Mutated NSCLC
Sacituzumab tirumotecan demonstrated a median overall survival of 20.0 months versus 13.5 months with docetaxel in pretreated EGFR-mutated NSCLC patients. The phase 2 OptiTROP-Lung03 study showed a hazard ratio of 0.63 for overall survival benefit with the TROP2-directed antibody-drug conjugate.
The TROP2-directed antibody-drug conjugate sacituzumab tirumotecan (sac-TMT) displayed a significant overall survival benefit compared with docetaxel in patients with pretreated EGFR-mutated non–small cell lung cancer according to data from the final OS analysis of the phase 2 OptiTROP-Lung03 study presented during the 2026 European Lung Cancer Congress. At a median follow-up of 23.8 months, patients who received sac-TMT achieved a median OS of 20.0 months compared with 13.5 months among patients who received docetaxel, representing a hazard ratio of 0.63.
The 18-month OS rates were 54.7% and 34.0%, respectively. After adjusting for crossover, the median OS in the sac-TMT arm was 20.0 months compared with 11.2 months in the docetaxel arm. The investigator-assessed median progression-free survival in the investigational arm was 7.9 months versus 2.8 months in the control arm, with a hazard ratio of 0.23.
In December 2024, the FDA granted breakthrough designation to sac-TMT for the treatment of patients with advanced or metastatic nonsquamous NSCLC harboring EGFR mutations whose disease has progressed on or following a TKI and platinum-based chemotherapy. OptiTROP-Lung03 enrolled patients with nonsquamous NSCLC who had either stage IIIB/IIIC disease and were ineligible for surgery or radical radiotherapy, or stage IV disease.
Patients were randomly assigned 1:1 to receive intravenous sac-TMT at 5 mg/kg every 2 weeks or IV docetaxel at 75 mg/m2 every 3 weeks. Treatment in both arms continued until disease progression, intolerable toxicity, or any other reason for discontinuation. The primary end point was overall response rate per blinded independent central review.
In terms of safety, any-grade treatment-related adverse effects occurred in 97.8% of patients in both the investigational and control arms. Patients in both arms experienced grade 3 or higher TRAEs (60.4% vs 73.9%), serious TRAEs (20.9% vs 41.3%), TRAEs leading to dose reduction (42.9% vs 43.5%), and TRAEs leading to dose interruption (46.2% vs 30.4%).
The most common any-grade TRAEs in the investigational arm included anemia (81.3%), decreased white blood cell count (74.7%), decreased neutrophil count (68.1%), and stomatitis (65.9%). The most common any-grade TRAEs in the control arm included anemia (67.4%), decreased white blood cell count (63.0%), decreased neutrophil count (58.7%), and alopecia (50.0%).