Table 2.
Ongoing targeted therapy trials in CCA.
| Target | Agents | Clinical Trial | Notes |
|---|---|---|---|
| IDH1 | Ivosidenib + Gemcitabine + cisplatin | NCT04088188, phase I | |
| Ivosidenib | NCT02073994 | ||
| LY3410738 ± (Gemcitabine + cisplatin) or durvalumab | NCT04521686, phase I | LY3410738 is a potent, selective, and covalent inhibitor of IDH1-R132 | |
| AG-120 (oral Ivosidenib) | NCT02073994, phase I | ||
| IDH305 | NCT02381886, phase I | For IDH1R132-mutant tumors only | |
| FGFR2 | oral infigratinib or gemcitabine + cisplatin | NCT03773302, phase III | |
| futibatinib or gemcitabine + cisplatin | NCT04093362 phase III | ||
| derazantinib | NCT03230318, phase II | Derazantinib is a potent FGFR1‒3 kinase inhibitor | |
| atezolizumab + derazantinib | NCT03230318 *, phase II | ||
| E7090 | NCT04238715 *, phase II | E7090 is a selective tyrosine kinase inhibitor against FGFR1-3 | |
| Pemigatinib or Gemcitabine + Cisplatin | NCT03656536 (FIGHT-302), phase III | ||
| RLY-4008 |
NCT04526106 (REFOCUS), phase I and II |
RLY-4008 is a potent and highly selective FGFR2 inhibitor | |
| KIN-3248 | NCT05242822, phase I | KIN-3248 is an oral small molecule FGFR inhibitor | |
| Futibatinib | NCT02052778, phase I and II | ||
| Bemarituzumab | NCT05325866, phase I | Bemarituzumab (FPA144) is a humanized, afucosylated immunoglobulin G1 monoclonal antibody (mAb) against FGFR2b | |
| BRAF | ABM-1310 | NCT05501912 *, phase I | |
| ABM-1310 ± cobimetinib | NCT04190628, phase I | Cobimetinib is a MEK inhibitor approved for the treatment of advanced melanoma | |
| NTRK | Entrectinib | NCT02568267, phase I | Entrectinib is a pan-TrkA/B/C, ROS1, and ALK inhibitor |
| HER2 | tucatinib + trastuzumab ± (pembrolizumab or FOLFOX or CAPOX) | NCT04430738, phase I and II | tucatinib is a selective tyrosine kinase inhibitor of HER2 |
| A166 | NCT03602079, phase I and II | A166 is an antibody-drug conjugate composed of a novel cytotoxic drug (Duo-5, anti-microtubule agent) | |
| CT-0508 | NCT04660929, phase I | CT-0508 is a biologic composed of adenovirally-transduced autologous macrophages containin Anti-HER2 Chimeric Antigen Receptor (CAR macrophages) | |
| tebotelimab ± margetuximab | NCT03219268, phase I | Tebotelimab is a DART molecule designed to bind PD-1 and LAG-3. Margetuximab is an anti-HER2 antibody. | |
| Zanidatamab |
NCT04466891 (HERIZON-BTC-01), phase II |
||
| Zanidatamab + XELOX or (FOLFOX ± bevacizumab) or (cisplatin + Gemcitabine or 5-FU) | NCT03929666 | ||
| DB-1303 | NCT05150691, phase I and II | DB-1303 is an antibody-drug conjugate |
* Non-US-based study.