Emerging Role of TROP2-Targeted Antibody–Drug Conjugates: A Comprehensive Review of Datroway and Its Regulatory Landscape

Abstract

Trophoblast cell-surface antigen 2 (TROP2) has emerged as a promising therapeutic target in the management of multiple solid malignancies due to its overexpression in various tumor types and association with poor clinical outcomes. Datroway (datopotamab deruxtecan) is a next-generation TROP2-targeted antibody–drug conjugate (ADC) designed to deliver a potent topoisomerase I inhibitor selectively to cancer cells while minimizing systemic toxicity. This review provides a comprehensive overview of Datroway, including its molecular design, mechanism of action, pharmacokinetic and pharmacodynamic characteristics, and current clinical development. Upon binding to TROP2-expressing tumor cells, Datroway undergoes receptor-mediated internalization, followed by intracellular release of its cytotoxic payload, leading to DNA damage, cell-cycle arrest, and apoptosis. Preclinical investigations have demonstrated significant antitumor activity across a range of solid tumors, while clinical studies have reported encouraging efficacy and an acceptable safety profile in patients with advanced or metastatic cancers. Frequently observed adverse events include nausea, stomatitis, fatigue, and hematological toxicities, whereas interstitial lung disease remains an important safety concern requiring vigilant monitoring. Recent regulatory approvals and ongoing clinical trials underscore the growing importance of Datroway in targeted cancer therapy. The integration of biomarker-guided patient selection and combination treatment strategies may further enhance its therapeutic value, establishing Datroway as a significant advancement in precision oncology.