Life sciences · Journal article
Expert Opinion on Biological Therapy · October 16, 2026
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INTRODUCTION: Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality, and resistance to targeted therapy and immunotherapy represents a substantial unmet clinical need. Trophoblast cell-surface antigen 2 (TROP2)-directed antibody-drug conjugates (ADCs) have emerged as a promising therapeutic class. AREAS COVERED: This drug evaluation summarizes the pharmacological rationale, molecular design, preclinical activity, clinical efficacy, safety profile, and regulatory development of sacituzumab tirumotecan (sac-TMT; MK-2870/SKB264) in NSCLC. Relevant evidence was identified through searches of PubMed, ClinicalTrials.gov, major oncology congress proceedings, and regulatory announcements through 20 September 2026. EXPERT OPINION: Randomized trials have demonstrated improved progression-free survival (PFS) with sac-TMT versus docetaxel and platinum-pemetrexed chemotherapy in epidermal growth factor receptor (EGFR)-mutated advanced NSCLC after EGFR tyrosine kinase inhibitor (EGFR-TKI) progression. In advanced NSCLC without actionable driver alterations, sac-TMT plus pembrolizumab improved PFS versus pembrolizumab alone in programmed death-ligand 1 (PD-L1)-positive disease; however, overall survival (OS) remains immature, and superiority over contemporary chemoimmunotherapy has not been established. The principal clinically relevant toxicities are hematologic toxicity and stomatitis. Future studies should clarify predictive biomarkers, optimal treatment sequencing, intracranial activity, and generalizability, while generating mature survival and quality-of-life data.