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)
Ye Chen1, Yue Zhang1, Chunyan Tian2
1First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, China.
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 lung cancer, driven by early phases and industry support. Diverse targets emphasize TROP2 and HER2, while biomarkers advance precision medicine from standard testing to personalized regimens. Novel targets and combinations enhance selectivity. Optimized linkers mitigate off-target risks, such as the risk of interstitial lung disease (ILD). This analysis offers researchers comprehensive insights and advocates for strengthened intercontinental collaboration and late-phase trials to improve patient outcomes.
Insights
Antibody-drug conjugates (ADCs) show rapid growth in lung cancer clinical trials, focusing on targets like TROP2 and HER2. Biomarkers are key for personalized medicine, with ongoing research into novel targets and combinations.
Area of Science:
- Oncology
- Clinical Pharmacology
- Biotechnology
Background:
- Antibody-drug conjugates (ADCs) represent a promising class of targeted cancer therapies.
- ADCs deliver cytotoxic agents directly to tumor cells, enhancing efficacy and minimizing systemic toxicity.
- The clinical trial landscape for ADCs in lung cancer requires comprehensive analysis.
Purpose of the Study:
- To systematically review and analyze registered clinical trials involving antibody-drug conjugates (ADCs) in lung cancer.
- To provide a comprehensive overview of the current ADC trial landscape, including trends, targets, and methodologies.
Main Methods:
- Systematic review of ADC trials in lung cancer registered in the Trialtrove database up to July 1, 2025.
- Analysis included trial numbers, geography, funding, phases, design, targets, linkers, payloads, and biomarkers.
- Followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
Main Results:
- 466 trials were included, showing exponential growth from 2001 to 2024.
- Trials were predominantly single-continent, industry-funded, and in early phases.
- Trophoblast cell surface antigen 2 (TROP2) and human epidermal growth factor receptor 2 (HER2) were top targets; 85.84% of trials featured biomarkers.
Conclusions:
- ADC trials in lung cancer are expanding rapidly, with a regional focus and significant industry investment.
- Biomarker utilization is increasing, supporting precision medicine approaches.
- Further intercontinental collaboration and late-phase trials are recommended to optimize patient outcomes.
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