The cholangiocarcinoma trial landscape in 2026
Cholangiocarcinoma has transformed from a therapeutically neglected malignancy to one of the most molecularly complex and commercially active rare oncology settings. The approvals of pemigatinib and infigratinib for FGFR2-fused intrahepatic CCA (iCCA), followed by ivosidenib for IDH1-mutated CCA, opened the era of molecularly targeted therapy in bile duct cancer. NTRK, BRAF, RET, and HER2 alterations have added additional actionable targets, making CCA one of the highest-density precision oncology settings in solid tumors.
The current competitive frontier is second-generation FGFR2 inhibitors overcoming resistance to first-generation agents, combinations of IO with targeted therapy, and, most recently, KRAS G12C-targeting agents entering CCA after the KRAS alteration was found in a meaningful fraction of extrahepatic CCA. For any BD, medical affairs, or investment professional following this space, the trial landscape requires daily attention.
Key CCA program categories to monitor:
- FGFR2 (iCCA-specific): Second-generation FGFR inhibitors (RLY-4008/lirafugratinib, NVL-520), combinations, and post-pemigatinib resistance settings
- IDH1 (iCCA/eCCA): Programs following ivosidenib, including combinations with venetoclax and IO agents
- KRAS G12C (eCCA/gCCA): Sotorasib and adagrasib combination studies, plus next-generation KRAS inhibitors
- Immunotherapy combinations: First-line durvalumab plus TOPAZ-1 standard of care vs. novel IO combinations
- ERBB2/HER2: Zanidatamab and other HER2-directed agents in HER2-amplified CCA (5–10% of cases)
- Pan-biomarker agnostic: NTRK (larotrectinib/entrectinib), BRAF V600E (dabrafenib/trametinib), RET inhibitors
Get daily cholangiocarcinoma trial digest
Filtered by molecular target, phase, and sponsor. Clean daily digest. Free plan, no credit card required.
Get the Free DigestA primary completion date pushed out, enrollment cut, or a primary endpoint changed in the last 90 days. Active trials only.
| Trial | Warning signs | Status |
|---|---|---|
| Polymeric Micellar Paclitaxel-Based Combination Therapy for Advanced Biliary… NCT07159204 | Primary completion moved at least 7 months later Primary endpoint removed Enrollment reduced 39% | Active, Not Recruiting |
22 more on the Trials at Risk page. See which trials →
Phase 2 and Phase 3 trials with a primary completion date in the next 180 days, as ClinicalTrials.gov estimates it today. Active trials only.
| Trial | Scheduled | Phase |
|---|---|---|
| Study of Novel Immunomodulators as Monotherapy and in Combination With… NCT05775159 | Oct 27, 2026 · Estimated | Phase 2 |
50 more on the Completions page. See the calendar →
What DataLookout monitors for cholangiocarcinoma
Configure your profile with keywords as specific or broad as your intelligence needs require. Examples:
- By histology/anatomy: "intrahepatic cholangiocarcinoma", "extrahepatic CCA", "perihilar bile duct cancer", "gallbladder cancer"
- By molecular target: "FGFR2 biliary", "IDH1 cholangiocarcinoma", "KRAS CCA", "HER2 bile duct"
- By mechanism: "FGFR inhibitor CCA", "IDH1 inhibitor biliary", "PD-L1 cholangiocarcinoma"
- By line of therapy: "first-line CCA", "second-line cholangiocarcinoma", "refractory bile duct cancer"
Who uses CCA trial monitoring
Oncology BD professionals
The cholangiocarcinoma space has attracted significant licensing activity. Relay Therapeutics' lirafugratinib (RLY-4008), a highly selective FGFR2 inhibitor, was a notable BD transaction. Janssen acquired a strong position through the FGFR inhibitor erdafitinib. Monitoring new Phase 2 trial initiations in FGFR2, IDH1, or KRAS CCA subsets allows BD teams to identify early-stage assets before clinical data becomes widely publicized.
Healthcare investors
CCA assets have driven significant valuation events. A Phase 3 trial initiation for a next-generation FGFR2 inhibitor in the post-pemigatinib setting, or a Phase 2 readout in KRAS G12C-mutated extrahepatic CCA, can drive material stock moves. Daily trial monitoring keeps analysts ahead of the news cycle.
Clinical development and medical affairs
Companies developing IO combinations in CCA following TOPAZ-1 and KEYNOTE-966 approvals monitor competitive Phase 3 activity continuously. The question of which IO combination will replace or complement gemcitabine/cisplatin/durvalumab as first-line standard of care is playing out in multiple ongoing Phase 3 trials.
Frequently asked questions
524 active trials, 303 recruiting.
Industry sponsors run 106 of these trials. The rest are run by universities, hospitals, government bodies and other non-commercial sponsors. The table below lists the 5 largest of 75.
| Top industry sponsor | Active trials |
|---|---|
| AstraZeneca | 11 |
| Eli Lilly and Company | 4 |
| Suzhou Suncadia Biopharmaceuticals Co., Ltd. | 4 |
| Merck (MSD) | 3 |
| Pfizer | 3 |
| Trial | Status | Latest tracked change | Seen |
|---|---|---|---|
| Perioperative Retlirafusp Alfa(Anti-PD-L1/TGF-β Bifunctional Fusion Protein)… NCT07847710 | Recruiting | Start date pushed from Aug 1, 2026 to Sep 30, 2026 | 2026-10-10 |
| Evaluating Novel Therapies in ctDNA Positive GI Cancers NCT05482516 | Active, Not Recruiting | Completion moved earlier from Dec 2028 to Dec 2027 | 2026-10-07 |
| A Study of PHST001 in Advanced Solid Tumors NCT06840886 | Recruiting | Interventions modified | 2026-10-06 |
| Modified Immune Cells (Autologous Dendritic Cells) and a Vaccine (Prevnar)… NCT03942328 | Recruiting | Completion moved earlier from Feb 28, 2031 to Aug 31, 2030 | 2026-10-06 |
| A Prospective Study of Sacituzumab Tirumotecan Plus Pembrolizumab for Advanced… NCT07850791 | Recruiting | Interventions modified | 2026-10-06 |
Each trial page shows every change DataLookout has recorded for that trial.
DataLookout checks ClinicalTrials.gov every day and records what changed on each trial: status, enrollment, phase, primary endpoint, completion dates, sites, sponsor, and the stated reason a trial stopped. Add a sponsor or a disease to your watchlist, or save any search, and the changes arrive in a daily or weekly email digest.
Free, $0 forever: 1 sponsor + 1 disease watchlist, 1 saved search in your email digest, track up to 5 individual trials, daily change detection, Trials at Risk (top 2 trials), the weekly report (top 3 trials). No credit card.
Pro, $49/month or $490/year: 10 sponsor + 10 disease watchlists, 10 saved searches in your email digest, track up to 25 individual trials, full Trials at Risk list, Completions calendar, the full weekly report, landscape reports, CSV export.