Antibody-drug conjugates in colorectal cancer: current landscape and future perspectives from clinical trials.

Advanced colorectal cancer (CRC) has limited therapeutic options. Antibody-drug conjugates (ADCs) deliver cytotoxic agents selectively, minimizing systemic toxicity.

This study outlines the current clinical trial landscape of ADCs in CRC to identify research gaps and future directions. We queried the Trialtrove database (up to August 2025) for non-observational trials of ADCs in CRC. Analytical indicators included temporal trends, geographic distribution, sponsor type, target antigens, and payloads. Overall, 194 eligible trials were identified.

Trial numbers have steadily increased since 2020, peaking in 2024. Most are open trials, predominantly conducted in China and the United States, and heavily industry-sponsored. HER2, Trop-2, and c-Met are the most frequently studied targets. Topoisomerase I inhibitors are the most common payloads, frequently paired with cleavable linkers.

Crucially, the vast majority of these trials remain in early phases (Phase I/II), with Safety and tolerability remaining the primary endpoints. ADCs show preliminary therapeutic potential in CRC; however, assertions regarding broad efficacy must remain highly cautious given the early-stage, safety-oriented nature of the current pipeline.

Furthermore, the current landscape faces challenges such as publication bias and industry dominance, which prioritize commercially viable hotspots over niche targets. Future progress relies on discovering novel targets, optimizing linker-payload designs, and exploring rational combination therapies.