Biliary Tract Cancer

P1, N=24, Active, not recruiting, University of Nebraska | Trial primary completion date: Oct 2025 --> May 2026

P2, N=57, Active, not recruiting, University Health Network, Toronto | Trial completion date: Dec 2025 --> Sep 2026 | Trial primary completion date: Dec 2024 --> May 2026

P2, N=10, Terminated, Genome & Company | Recruiting --> Terminated | N=148 --> 10; Sponsor decision

This study demonstrates a role of platinum-based chemotherapy on HSC activation in liver cancer. Selective targeting of PI3K p110α may provide a novel strategy to inhibit chemotherapy-induced HSC activation and improve treatment response.

Combining targeted therapies with immune checkpoint inhibitors showed promising results in two patients with advanced BTC driven by specific genetic mutations. Significant tumor reduction and successful surgeries suggest this approach may improve resectability and outcomes. These cases highlight the potential of personalized treatment guided by genetic profiling. Further research is needed to confirm these findings and explore broader applications for this strategy.

Patients with advanced AC formed the "Descriptive cohort," while those treated with cisplatin-gemcitabine (CisGem) comprised the "CisGem-treated cohort." Among 534 trial participants, 28 (5.24%) had AC, and 17 received CisGem. Molecular profiling has revealed potentially actionable alterations, including HER2 amplification and KRAS mutations, supporting precision oncology approaches. This study provides the most comprehensive reference dataset to date for advanced AC treated with CisGem and emphasizes the importance of international collaboration and molecularly guided research to improve outcomes in this rare malignancy.

P=N/A, N=250, Recruiting, Institute of Liver and Biliary Sciences, India | Not yet recruiting --> Recruiting

CA125 and hepcidin as quantitative markers, along with PIVKA-II as a qualitative marker, demonstrate significant potential as biliary markers for distinguishing choledocholithiasis from biliary tract or pancreatic cancers. Biliary iron, TIBC, and CA19-9 require further investigation to confirm their diagnostic yield.

Finally, we identify current limitations in the field, including inconsistent CLDN18.2 testing criteria, and outline prioritized future directions to optimize integration of CLDN18.2-directed therapies across gastrointestinal cancers. By looking beyond zolbetuximab and incorporating cross-platform comparison, immuno-oncology considerations, and multi-tumor context, this review provides a broad and forward-looking framework to guide clinical application and next-generation research in CLDN18.2-targeted therapy.

P1/2, N=160, Not yet recruiting, Yonsei University

P1, N=48, Not yet recruiting, Washington University School of Medicine | Trial completion date: Dec 2031 --> Apr 2032 | Initiation date: Oct 2025 --> Feb 2026 | Trial primary completion date: Jan 2030 --> May 2030