Evolution and recent advances in antibody-drug conjugate therapy for lung cancer: a comprehensive systematic review based on the Trialtrove database (inception to July 1, 2025)
Abstract
Background: Antibody-drug conjugates (ADCs) are emerging targeted therapies in cancer treatment. They selectively deliver cytotoxic payloads to tumor cells, improving efficacy and reducing toxicity. However, the clinical trial landscape in lung cancer remains unclear. This systematic review analyzes registered ADC trials in lung cancer comprehensively.
Methods: Trials were retrieved from the Trialtrove database from inception to July 1, 2025, focusing on ADC interventions in lung cancer. The inclusion criteria required complete ADC data, excluding observational studies or incomplete records. The analyses covered trial numbers, geography, funding, phases, design, targets, linkers, payloads, and biomarkers. This review follows Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
Results: A total of 546 global trials were identified, of which 466 were included. The trial registrations grew exponentially from one in 2001 to 106 in 2024. Most trials were single-continent and industry-funded. Early phases predominated. A total of 76 targets were involved, with the top 15 (e.g., trophoblast cell surface antigen 2 (TROP2), 18.07%; human epidermal growth factor receptor 2 (HER2), 17.65%) accounting for 78.15%. The linkers were mainly cleavable protease-dependent. Payloads were dominated by DNA topoisomerase I inhibitors. Biomarkers were featured in 85.84% of trials.
Conclusion: This review highlights the rapid expansion and regional focus of ADC trials in…
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