Table 2.

List of Completed and Ongoing Clinical Trial Evaluating Selected Targeted Agents in CCA

Target	Agents	Available Data from Completed Trials	Ongoing
FGFR (FGFR-2 fusion/re-arrangement)	Pemigatinib*	Phase 2 FIGHT 202 trial: ORR - 35.5% mOS - 21.1 mos	FIGHT-302 – [NCT03656536] Phase 3 – front line vs gemcitabine + cisplatin
	Futibatinib (TAS-120)	Phase 2 trial FOENIX-CCA2: ORR - 37.7% DCR – 82% mPFS – 7.2 mos	FOENIX-CCA3 – [NCT04093362] Phase 3 – front line vs gemcitabine + cisplatin
	Infigratinib* (BGJ398)	Phase 2 trial: ORR - 23.1%% mPFS – 7.3 mos mOS – 12.2m	PROOF trial – [NCT03773302] Phase 3 - front line vs gemcitabine + cisplatin
	Derazantinib (ARQ087)108	Phase 1/2: ORR - 20.7% DCR – 82.8% mPFS - 5.7m	FIDES-01- [NCT03230318] Phase 2 – 2nd line therapy
	ICP-192	N/A	Phase 1 evaluating single agent activity in advanced CCA and other solid tumors [NCT04565275]
IDH	Ivosidenib* (AG-120)	ClarIDHy phase 3 study vs placebo: mPFS - 6.9m vs 1.4m mOS − 10.8m vs 9.7m	Phase 1 front line in combination with gemcitabine and cisplatin [NCT04088188]
	Enasidenib (AG-221)	N/A	Phase 1 results evaluating single agent activity in advanced CCA and other solid tumors with IDH2 mutations [NCT02273739]
	Olaparib	N/A	Phase 2 evaluating single agent activity in IDH1 and IDH2 mutated CCA [NCT03212274]
	Olaparib + ceralasertib AZD 6738 (ATR inhibitor)	N/A	Phase 2 evaluating the combination in IDH1 and IDH2 mutated CCA [NCT03878095]
	Olaparib +Durvalumab	N/A	Phase 2 evaluating the combination in IDH1 and IDH2 mutated CCA [NCT03991832]
	LY3410738	N/A	Phase 1 evaluating single agent in IDH mutated CCA and other solid tumors [NCT04521686]
	Olutasidenib (FT-2102)	N/A	Phase 1/2 evaluating single agent activity in advanced CCA and other solid tumors with IDH1 mutations [NCT03684811]
DNA Repair Gene mutations	Olaparib	N/A	Phase 2 evaluating single agent activity in advanced CCA with aberrant DNA repair gene mutations (i.e: BRCA, PALB2, ATM, ATR, etc.) [NCT04042831]
	Niraparib	N/A	Phase 2 evaluating single agent activity in advanced CCA and other solid tumors with aberrant DNA repair gene mutations in BAP1 and other genes (i.e: PALB2, ATM, ATR, etc.) [NCT03207347]
HER2	Varlitinib109	Randomized Phase 2 TREETOPP study [NCT03093870] - Capecitabine ± Varlitinib: ORR 9.4% vs 4.8% No difference in mPFS or mOS	N/A
	Trastuzumab + Pertuzumab	Phase 2 study of multiple HER2 overexpressing or amplified tumors. Data from small cohort of advanced CCA patients – ORR- 37.5% for HER2 over expression. [NCT02091141]	N/A
	Trastuzumab + Tucatinib	N/A	Basket study evaluating the combination in advanced CCA and other solid tumors harboring HER2 alterations [NCT04579380]
	Trastuzumab + Tucatinib + FOLFOX	N/A	Phase 1/2 evaluating the combination in HER2 positive advanced CCA and other GI cancers [NCT04430738]
	Lapatanib110	Open label phase 2 closed early due to futility. No responses seen.	N/A
	Zanidatamab (ZW25)	N/A	Phase 2 study evaluating single agent activity in HER2 positive advanced CCA [NCT04466891]
	Trastuzumab deruxtecan	N/A	Phase 2 study evaluating single agent activity in HER2 positive advanced CCA and other solid tumors. [NCT04482309]
BRAF V600E mutation	Dabrafenib + Trametinib	Phase 2 (ROAR) basket trial showing 51% ORR in advanced CCA patients. [NCT02034110]	N/A
PI3K	Copanlisib111	Phase 2 study in combination with gemcitabine and cisplatin in 1st line did not meet the primary end point of improved 6m PFS [NCT02631590]	N/A

Note: *FDA-approved targeted therapy.

Abbreviations: ORR, objective response rate; mPFS, median progression free survival; mOS, median overall survival; ATR, ataxia telangiectasia and RAD3 related (ATR) kinase.