Table 2.
Target agents in clinical development.
| Target | Drug | Study Design | Significance | Ref. or Clinical Trial.gov |
|---|---|---|---|---|
| IDH 1 and 2 | ||||
| IDH1 mutation | Ivosidenib | Phase III | Phase III trial evaluating the efficacy of AG120 in previously treated advanced CCA patients with IDH1 mutations (ClarIDHy) | Abou-Alfa ESMO 2019 [38] |
| FGFR Selective and Non-selective Inhibitors | ||||
| FGFR2 | BGJ398 | Phase II | Evaluate the activity of BGJ398 in patients with FGFR genetic alterations positive advanced CCA | NCT02150967 |
| FGFR2 | BGJ398 | Phase III | Phase III trial evaluating the efficacy of BGJ298 + Cisplatin + Gemcitanine vs. Cisplatin + Gemcitabine alone in FGFR2 positive CCA | NCT03773302 |
| FGFR pathway alterations | Erdafitinib | Phase I | Solid tumors/CCA | NCT02699606 |
| FGFR mutation/Fusion | Derazantinib | Phase II | Evaluate the activity and the efficacy of derazantinib in patients with FGFR genetic alterations positive advanced iCCA | NCT03230318 |
| FGFR mutation/Fusion | Derazantinib | expanded access | Investigational drugs outside of the clinical trial setting | NCT04087876 |
| FGFR rearrangements/mutations | TAS-120 | Phase I-II | Evaluate the efficacy in patients with FGFR gene rearrangements positive advanced iCAA | NCT02052778 |
| FGFR rearrangements | TAS-120 | Phase III/TAS-120 vs. Cisplatin Gemcitabine | Evaluate the efficacy in patients with FGFR gene rearrangements positive advanced iCCA | NCT04093362 |
| FGFR1-2-3 Gene Alteration |
Pemigatinib | Phase I | Evaluate the safety and MTD of Pemigatinib + Cisplatin + Gemcitabine in patients with advanced CCA | NCT04088188 |
| FGFR2 rearrangement. | Pemigatinib | Phase III | Phase III trial evaluating the efficacy of Pemigatinib vs. Cisplatin + Gemcitanine in FGFR2 positive CCA | NCT03656536 |
| HER Family (ERBB2) Receptors | ||||
| HER2 | Trastuzumab | Phase II | Phase II trial evaluating the activity of trastuzumab in patients with HER2/neu-positive advanced gallbladder or CCA | NCT00478140 |
| HER2 | Trastuzumab Emanstine | Phase II | Phase II trial evaluating the activity of trastuzumab emanstine in patients with HER2/neu-positive advanced gallbladder or CCA | NCT02999672 |
| MAPK Pathway | ||||
| BRAF | Dabrafenib and trametinib | Phase I | Evaluate the Activity and Safety of the combination regimen in subjects with BRAF V600E- Mutated Rare Cancers including CCA | NCT02699606 |
| Angiogenesis and Non-selective Kinase Inhibitors | ||||
| VEGFR2 | Ramucirumab | Phase II | Phase II trial evaluating the efficacy of Ramucirumab or Merestinib or Placebo Plus Cisplatin and Gemcitabine | NCT02711553 |
| VEGFR2 | Ramucirumab-Pembrolizumab | Phase I | Phase I trial evaluating the safety and the activity of Pembrolizumab and Ramucirumab in solid tumors | NCT02443324 |
| ROS1 and Neurotrophic Tyrosine Kinase Receptor (TRKA) | ||||
| NTRK 1/2/3 (Trk A/B/C), ROS1, or ALK | Entrectinib | Phase II | Evaluate the Activity entrectinib in subjects with gene rearrangement of NTRK 1/2/3/ROS1/ALK in solid tumors including CCA | NCT02568267 |
| Multiple Targets | Gemcitabine-Pazopanib | Phase II | Evaluate the Activity of Gemcitabine-Pazopanib in patients with advanced CCA | NCT01855724 |
1 CCA = cholangiocarcinoma. 2 iCCA = intrahepatic cholangiocarcinoma.