Gemcitabine + Cisplatin + Durvalumab + Pemigatinib for Bile Duct Cancer

This trial tests a new treatment combination for bile duct cancer that cannot be surgically removed or has spread. The study examines the effectiveness of combining chemotherapy drugs (gemcitabine and cisplatin), an immunotherapy drug (durvalumab), and a targeted cancer drug (pemigatinib). These drugs aim to halt cancer growth and enhance the immune system's ability to fight cancer. Suitable candidates have bile duct cancer with specific FGFR2 gene changes and have not received certain prior treatments. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

The trial protocol does not specify if you need to stop taking your current medications. However, you should avoid certain drugs that affect liver enzymes (CYP3A4 inhibitors or inducers) and immunosuppressive medications before and during the trial. It's best to discuss your current medications with the trial team.

A previous study showed that combining gemcitabine, cisplatin, and durvalumab improved survival rates compared to chemotherapy alone. Adding durvalumab, an immunotherapy drug, may enhance cancer treatment effectiveness. Importantly, research found that durvalumab did not cause many additional side effects, suggesting the treatment is manageable.

Pemigatinib, another drug under testing, blocks signals that promote cancer cell growth. Although specific safety data for pemigatinib in this trial is unavailable, its approval for other uses indicates its safety in those contexts.

Researchers are excited about this combination treatment for bile duct cancer because it brings together chemotherapy, immunotherapy, and targeted therapy in a novel way. Cisplatin and gemcitabine are standard chemotherapy drugs that kill cancer cells, but adding durvalumab, an immunotherapy, helps the immune system better recognize and attack the cancer. Additionally, pemigatinib is a targeted therapy that specifically inhibits FGFR (fibroblast growth factor receptor), which can be overactive in some bile duct cancers. This multi-pronged approach could potentially improve outcomes by attacking the cancer on multiple fronts, offering hope where traditional treatments alone might fall short.

This trial will evaluate the combination of gemcitabine, cisplatin, and durvalumab with pemigatinib for treating advanced biliary tract cancer. Research has shown that adding durvalumab to gemcitabine and cisplatin increased survival time to 12.9 months, compared to 11.3 months with just chemotherapy. For patients using these drugs, the average survival was about 14 months, and 65.5% of patients experienced either tumor shrinkage or stability. Pemigatinib targets a protein that aids cancer growth, and studies have shown it can help control the disease in some patients. Together, these treatments aim to slow cancer growth and improve survival for individuals with difficult-to-treat bile duct cancers.¹²⁶⁷⁸