Final OptiTROP-Lung04 OS: Sacituzumab Tirumotecan Reaches Median OS of 25.9 Months

EGFR mutation is the most common driver alteration in advanced nonsquamous NSCLC in China; the prospective PIONEER epidemiology study detected an EGFR mutation rate of 51.4% among 1482 Asian patients with advanced lung adenocarcinoma ［peer-reviewed·J］, while nearly all patients eventually acquire resistance after first-line third-generation EGFR-TKI, and platinum-based chemotherapy offers limited efficacy, leaving a long-standing unmet need. Sacituzumab tirumotecan (SKB264/MK-2870) is a TROP2 ADC developed by Kelun-Biotech on its proprietary OptiDC™ platform. OptiTROP-Lung04 (NCT05870319) is a multicenter randomized open-label phase 3 registration study in China; the registry records its start on 2023-06-26, a planned enrollment of 376 patients, and BICR-assessed PFS as the primary endpoint .

The final OS analysis (LBA67) presented at the 2026 ESMO Congress showed that at a median follow-up of 32.3 months, the sacituzumab tirumotecan group achieved a median OS of 25.9 months versus 17.4 months with platinum-based chemotherapy, an 8.5-month gain with a 31% reduction in risk of death (HR=0.69, 95%CI 0.54-0.89, P=0.0021); 24-month OS rates were 54.1% vs 37.2%, and 30-month OS rates were 40.5% vs 28.4%. After RPSFT model adjustment for crossover, median OS was 25.9 vs 16.6 months, a 9.3-month gain with a 43% risk reduction (adjusted HR=0.57, 95%CI 0.42-0.75). The primary endpoint previously showed median PFS of 8.3 vs 4.3 months (HR=0.49, P<0.0001) and ORR of 60.6% vs 43.1%; these data were peer-reviewed and published in the New England Journal of Medicine, which reported median PFS of 8.3 vs 4.3 months at a median follow-up of 18.9 months ［peer-reviewed·C］, with significantly longer OS ［peer-reviewed·E］ (needs verification).

This final OS analysis extends follow-up from the 18.9 months at first report ［peer-reviewed·C］ to 32.3 months, confirming the durability of survival benefit. Despite dilution from post-progression crossover therapies including other ADCs in the control arm, the OS improvement remained statistically significant and was further amplified after crossover adjustment. In the enrolled population, 94.7% had prior third-generation TKIs and nearly 70% had high tumor burden; benefit was consistent across prespecified subgroups (brain metastases, liver metastases, ≥3 metastatic sites). On safety, median exposure in the sac-TMT arm was 9.4 months, twice the 4.9 months of chemotherapy; grade ≥3 TRAE rates were similar (58.5% vs 53.8%), serious TRAEs were notably lower (10.1% vs 18.1%), and there were no TRAE-related permanent discontinuations. Professor Zhang Li noted this is the world's first phase 3 study in which a single agent achieved both significant PFS and OS improvement in EGFR-TKI-resistant advanced NSCLC, and that its path of precise population identification, mechanistic validation, and successful registration study offers a reference for ADC development in other tumor types. The indication has been approved by NMPA; the prior success of OptiTROP-Lung03 supported approval in advanced NSCLC after EGFR-TKI and platinum chemotherapy failure and inclusion in the national reimbursement drug list (needs verification).

Looking forward, the registration phase 3 OptiTROP-Lung07 study led by Professor Zhang's team in China is evaluating sacituzumab tirumotecan plus osimertinib versus osimertinib monotherapy as first-line treatment for EGFR-mutated locally advanced/metastatic nonsquamous NSCLC; preclinical data suggest TROP2 upregulation on drug-tolerant persister cells after TKI treatment, providing mechanistic support. Detailed subgroup OS data, enrollment status, and timelines for OptiTROP-Lung07 are not yet disclosed and await future congress presentations and registry updates (needs verification).