Biliary Tract Cancer

P1/2, N=290, Recruiting, Crescent Biopharma, Inc. | Not yet recruiting --> Recruiting

P2, N=30, Active, not recruiting, First Affiliated Hospital of Zhejiang University | Recruiting --> Active, not recruiting | Trial completion date: Sep 2025 --> Dec 2026

Selective FGFR tyrosine kinase inhibitors, including the reversible inhibitor pemigatinib and the irreversible inhibitor futibatinib, have demonstrated clinically meaningful response rates and durable disease control in patients with previously treated FGFR2-altered iCCA, leading to regulatory approvals and the incorporation of FGFR inhibition into contemporary treatment paradigms. In addition, we highlight the growing role of circulating tumor DNA as a noninvasive tool for longitudinal molecular monitoring and treatment guidance. Together, these insights underscore the central role of FGFR2-directed therapy in precision oncology for biliary tract cancer and provide a framework for optimizing and extending targeted treatment in this molecularly defined disease subset.

P2, N=224, Recruiting, AstraZeneca | Trial completion date: Dec 2026 --> Sep 2027 | Trial primary completion date: Dec 2025 --> Aug 2026

P2, N=160, Not yet recruiting, OHSU Knight Cancer Institute

Adding ivosidenib to gemcitabine and cisplatin in this study demonstrated a challenging safety profile in advanced CCA. Further research and dose optimization are warranted to confirm these findings and optimize the integration of targeted therapies into first-line regimens.

Standardized molecular testing strategies will be key to enable the integration of more consistent and comparable genomic datasets across studies. Further, by elucidating the prognostic relevance of individual genomic alterations, our insights carry significant implications for interpreting single-arm clinical trials within genomically stratified patient cohorts and underscore the importance of randomized studies to delineate the benefit of targeted therapies.

P1, N=91, Recruiting, Adlai Nortye Biopharma Co., Ltd. | Not yet recruiting --> Recruiting

Our study revealed that DNA damage response altered the tumor structure and modulated the expression of multiple genes, including extracellular matrix- and immune-related genes. Studies using in vitro organoid models can be useful for investigating three-dimensional cellular responses after DNA-damaging cancer therapies, such as chemoradiotherapy.

Pembrolizumab plus lenvatinib with reduced-dose GEMOX demonstrated promising efficacy and a favorable safety profile in advanced BTC, suggesting that chemotherapy de-escalation may optimize the efficacy-toxicity balance. Further randomized studies are warranted to confirm these findings and refine biomarker-based treatment selections.

P1/2, N=29, Recruiting, Tongji Hospital

As the burden of early-onset PBTCs grows, refining screening strategies and integrating microbiome-based risk assessment into biobanking strategies will be critical. Future research should focus on age-stratified genetic risk profiling, microbiota-driven interventions, and personalized therapeutic approaches to improve early detection and patient outcomes.