OptiTROP-Lung03 Evaluates Sacituzumab Tirumotecan in EGFR-Mutated NSCLC

Sacituzumab tirumotecan (sac-TMT) showed greater survival benefits and fewer treatment-related adverse events (TRAEs) compared with docetaxel among patients with previously treated advanced EGFR-mutated non–small cell lung cancer (NSCLC), according to findings from the OptiTROP-Lung03 trial.

Li Zhang, MD, of Sun Yat-sen University Cancer Center, Guangzhou, China, and colleagues investigated the novel trophoblast cell-surface antigen 2 (TROP2)–directed antibody drug conjugate (ADC) in comparison with platinum-based chemotherapy. Zhang presented the findings from the multicenter, randomized, controlled study at the 2025 American Society of Clinical Oncology Annual Meeting.

The primary end point was objective response rate (ORR) assessed by blinded independent review committee (BIRC), with secondary end points of progression-free survival (PFS) and overall survival (OS).

Patients enrolled in the study (n=137) were a median age of 56 years, and 43.8% were men. All patients had advanced EGFR-mutated NSCLC disease that had progressed after EGFR tyrosine kinase and platinum-based chemotherapy treatment. Most of the patients (82.5%) had an Eastern Cooperative Oncology Group (ECOG) performance status of 1.

The researchers randomized patients 2:1 to receive sac-TMT (n=91) 5 mg/kg once every 2 weeks or docetaxel (n=46) 75 mg/m². Crossover from the docetaxel arm to the sac-TMT arm was allowed if patients were eligible.

In this patient population, sac-TMT demonstrated improved ORR and PFS compared with docetaxel. At a median follow-up of 12.2 months, 25.3% of patients treated with sac-TMT versus 4.3% treated with docetaxel continued therapy.

Compared with docetaxel (ORR, 15.6%), sac-TMT achieved statistically significant clinical outcomes with an ORR of 45.1% (BIRC). Moreover, PFS improved in the sac-TMT arm versus the docetaxel arm (BIRC: median 6.9 months vs 2.8 months, respectively). Median OS was not reached in either arm.

In the docetaxel arm, 36.4% of patients crossed over to receive sac-TMT. The rank-preserving structural failure time model adjusted median OS was 9.3 months for docetaxel but was not reached for sac-TMT.

In addition, sac-TMT had a better safety profile than docetaxel. Just over half (56%) of patients in the sac-TMT arm experienced grade 3 or higher TRAEs compared with 71.7% in the docetaxel arm. The most common TRAEs in the sac-TMT and docetaxel arms were decreased neutrophil count (42.9% vs 58.7%), decreased white blood cell count (25.3% vs 52.2%), stomatitis (16.5% vs 2.2%), anemia (12.1% vs 4.3%), and febrile neutropenia (0% vs 19.6%), respectively.

Serious AEs related to treatment occurred in 16.5% of patients in the sac-TMT arm compared with 41.3% in the docetaxel arm. There were no cases of interstitial lung disease in the sac-TMT arm.

“These results highlight significant survival benefits and suggest that sac-TMT could emerge as a new standard of care for this population,” the researchers said.