Oncology · Clinical trials
Cholangiocarcinoma Clinical Trials
Approved therapies, the pivotal-trial endpoints they were judged on, the magnitude of benefit — and the drugs that failed their endpoints, and why.
Indication overview
About cholangiocarcinoma — and why its trials are hard
Cholangiocarcinoma is a rare, aggressive malignancy of the intrahepatic, perihilar, or distal bile ducts, often diagnosed late when surgery is no longer curative. For decades the only systemic standard was gemcitabine plus cisplatin (ABC-02), leaving a stark unmet need. The landscape shifted sharply after 2020: adding the PD-L1 inhibitor durvalumab to gemcitabine/cisplatin (TOPAZ-1) became the first immunotherapy standard for advanced biliary tract cancer, and pembrolizumab plus the same backbone (KEYNOTE-966) followed. Molecular profiling now guides second-line therapy, with FGFR2 fusions (present in 10-15% of intrahepatic tumors) targeted by pemigatinib and futibatinib, and IDH1 mutations addressed by ivosidenib. Despite these advances, response rates and survival gains remain modest, resistance emerges quickly, and no targeted option exists for the majority of patients lacking actionable alterations. Biomarker testing at diagnosis is now essential, and combination and next-generation FGFR strategies are active research priorities in a still high-mortality disease.
Approved therapies & pivotal evidence
What's been approved — and by how much it moved the endpoint
| Drug (brand) | Approved | Setting | Pivotal trial | Primary endpoint | Magnitude of benefit |
|---|---|---|---|---|---|
| Durvalumab (Imfinzi) | 2022 | First-line, advanced/metastatic biliary tract cancer, with gemcitabine + cisplatin | TOPAZ-1 (phase 3) | Overall survival | Median OS 12.8 vs 11.5 mo, HR ~0.80; durable tail with ~25% alive at 2 years |
| Pembrolizumab (Keytruda) | 2023 | First-line, advanced/metastatic biliary tract cancer, with gemcitabine + cisplatin | KEYNOTE-966 (phase 3) | Overall survival | Median OS 12.7 vs 10.9 mo, HR 0.83 |
| Pemigatinib (Pemazyre) | 2020 | Previously treated, unresectable/metastatic cholangiocarcinoma with FGFR2 fusion/rearrangement | FIGHT-202 (phase 2) | Overall response rate (accelerated approval) | ORR ~36%, median DOR ~9 mo |
| Ivosidenib (Tibsovo) | 2021 | Previously treated, advanced/metastatic cholangiocarcinoma with IDH1 mutation | ClarIDHy (phase 3) | Progression-free survival | Median PFS 2.7 vs 1.4 mo, HR 0.37; OS benefit confounded by crossover |
| Futibatinib (Lytgobi) | 2022 | Previously treated, unresectable/metastatic intrahepatic cholangiocarcinoma with FGFR2 rearrangement | FOENIX-CCA2 (phase 2) | Overall response rate (accelerated approval) | ORR ~42%, median DOR ~9.7 mo |
Where trials have failed
Drugs that missed their endpoint — and what contributed
The most instructive lessons in cholangiocarcinoma development come from programmes that failed the endpoint that mattered.
| Drug / trial | Endpoint outcome | What contributed |
|---|---|---|
| Varlitinib — TreeTopp (phase 2/3) | Failed to significantly improve ORR or PFS with capecitabine in second line | Pan-HER inhibition without biomarker selection; limited single-agent activity |
| Infigratinib — CBGJ398X2204 | Approved 2021 for FGFR2 fusions but voluntarily withdrawn from the market in 2022 | Commercial/business decision amid competition from other FGFR inhibitors, not efficacy failure |
Choosing the right endpoint
Primary endpoints that matter in cholangiocarcinoma trials
- Overall survival (OS) — Gold-standard endpoint anchoring first-line chemo-immunotherapy approvals (TOPAZ-1, KEYNOTE-966)
- Progression-free survival (PFS) — Primary endpoint for targeted second-line agents such as ivosidenib in ClarIDHy
- Overall response rate (ORR) — Basis for accelerated approvals of FGFR2 inhibitors pemigatinib and futibatinib
- Duration of response (DOR) — Key supportive measure of clinical benefit durability for single-arm targeted trials
- FGFR2/IDH1 biomarker status — Molecular selection determines eligibility for targeted therapy in the second-line setting
How iNGENū runs cholangiocarcinoma trials
Physician-led design, built for FDA submission
Endpoint & biomarker strategy
Board-certified specialists design endpoints and patient selection aligned to current FDA guidance for this indication.
FDA-ready data
Built to ICH-GCP and 21 CFR 312.120, with direct FDA submission — data accepted by the FDA, EMA and MHRA.
Faster, lower-cost delivery
~4-week ethics via the TGA CTN scheme, up to 43.5% R&D rebate, and 80–90% below US CRO cost.
Request a fixed-milestone proposal and a tailored endpoint & feasibility summary for this indication.
Frequently asked questions
Cholangiocarcinoma clinical trials — FAQs
Which cholangiocarcinoma patients should receive molecular testing?
What is the current first-line standard of care?
Why is survival still poor despite new drugs?
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