. 2023 Oct 27;63(6):137. doi: 10.3892/ijo.2023.5585

Table I.

Clinical trials of immunotherapy regimens for CCA.

	Trial number	Phase	Line of treatment	Type of BTC	Estimated enrollment	Allocation	Study arms		Pathways targeted	Primary outcomes	Status
	Trial number	Phase	Line of treatment	Type of BTC	Estimated enrollment	Allocation	Arm A	Arm B	Pathways targeted	Primary outcomes	Status
Monotherapy	NCT04157985	3	First-line	CCA	578	Randomized	Pembrolizumab or nivolumab or atezolizumab or ipilimumab or cemiplimab	N/A	PD-1/PD-L1	Time to next treatment, PFS	Recruiting
	NCT03110328	2	Second-line	CCA	33	N/A	Pembrolizumab	N/A	PD-1	Best overall response, PFS, OS	Completed
	NCT02054806	1b	Second- or later-line	CCA, GBC	477	N/A	Pembrolizumab	N/A	PD-1	Best overall response	Completed
	NCT02829918	2	Second- or later-line	CCA, GBC	54	N/A	Nivolumab	N/A	PD-1	ORR After 4 Cycles of Treatment	Active, not recruiting
	NCT03999658	2	Second- or later-line	CAA, GBC	220	Non-randomized	STI-3031	N/A	PD-L1	ORR	Not yet recruiting
	NCT02628067	2	Second- or later-line	CCA, GBC	1,609	Non-randomized	Pembrolizumab	N/A	PD-1	ORR	Recruiting
	NCT03201458	2	Second- or later-line	CCA, GBC	76	Randomized	Atezolizumab	Atezolizumab plus cobimetinib	PD-L1, MEK1	PFS	Active, not recruiting
	NCT04238637	2	Second- or later-line	ICC	50	Randomized	Durvalumab	Durvalumab plus tremelimumab	PD-L1, CTLA-4	ORR	Recruiting
	NCT04440943	1	Second- or later-line	CCA	40	N/A	CDX-527	N/A	PD-L1xCD27	Safety, tolerability	Recruiting
	NCT05101109	1	Second- or later line	N/A	36	N/A	ABL501	N/A	LAG-3xPD-L1	Safety, tolerability	Recruiting
	NCT03849469	1	Second- or later-line	ICC	242	Non-Randomized	XmAb^® 22841	XmAb^® 22841 plus pembrolizumab	CTLA-4xLAG-3, PD-1	Safety, tolerability	Active, not recruiting
	NCT03517488	1	Second- or later-line	CCA	154	N/A	XmAb^® 22842	N/A	CTLA-4xLAG-3	Safety, tolerability	Active, not recruiting
	NCT03219268	1	Second- or later-line	CCA	353 N/A	Tebotelimab	Tebotelimab plus margetuximab	PD-1xLAG-3, HER2	Safety, tolerability	Active, not recruiting
	NCT04802876	2	N/A	CCA	141N/A	Spartalizumab	N/A	PD-1	ORR	Recruiting
ICIs + chemotherapy	NCT04066491	2/3	First line	CCA, GBC	309 Randomized		M7824 plus GC GC	Placebo plus L1xTGF-β	PD-	Safety, OS recruiting	Active, not
	NCT03046862	2	First-line	CCA, GBC	31 N/A	Durvalumab or tremelimumab plus GC	N/A	PD-L1, CTAL-4	ORR	Active, not recruiting
	NCT03875235	3	First-line	CCA, GBC	810 Randomized	plus GC	Durvalumab GC	Placebo plus	PD-L1	OS recruiting	Active, not
	NCT04003636	3	First-line	CCA, GBC	1,048 Randomized	plus GC	Pembrolizumab GC	Placebo plus	PD-1	OS recruiting	Active, not
	NCT03260712	2	First-line	CCA, GBC	50 N/A	Pembrolizumab plus GC	N/A	PD-1	PFS at 6 months	Active, not recruiting
	NCT03796429	2	First-line	CCA, GBC	40 N/A	Toripalimab plus GS	N/A	PD-1	PFS, OS	Recruiting
	NCT04172402	2	First-line	CCA, GBC	48 N/A	Nivolumab plus GS	N/A	PD-1	ORR	Active, not recruiting
	NCT04027764	2	First-line	CCA, GBC	30 N/A	Toripalimab plus S1 plus albumin paclitaxel	N/A	PD-1	ORR	Recruiting
	NCT03478488	3	First-line	CCA, GBC	480 Randomized	GEMOX	KN035 plus	GEMOX	PD-L1	OS	Recruiting
	NCT03785873	1b/2	Second-line	CCA, GBC	34 N/A	Nivolumab plus 5-FU plus Nal-Irinotecan	N/A	PD-1	Safety, tolerability, PFS	Active, not recruiting
	NCT03704480	2	Second-line	CCA, GBC	102 Randomized	plus tremelimumab	Durvalumab plus tremelimumab plus Paclitaxel	Durvalumab CTLA-4	PD-L1,	PFS	Recruiting
	NCT03111732	2	Second- or later-line	CCA, GBC	11	N/A	Pembrolizumab plus oxaliplatin plus capecitabine	N/A	PD-1	PFS	Completed
	NCT03101566	2	N/A	CCA, GBC	75	Randomized	Nivolumab plus GC	Nivolumab plus ipilimumab	PD-1, CTLA-4	PFS at 6 months	Active, not recruiting
	NCT04295317	2	N/A	ICC	65	N/A	SHR-1210 plus capecitabine	N/A	PD-1	RFS	Recruiting
	NCT03311789	1/2	N/A	CCA,	30	N/A GBC	Nivolumab or SHR-1210 plus GC	N/A	PD-1	PFS at 6 months	Recruiting
ICIs + targeted therapy	NCT04361331	2	First-line	ICC	60	Randomized	Toripalimab plus lenvatinib	Lenvatinib plus GEMOX	PD-1, TKI	ORR	Active, not recruiting
	NCT03895970	2b	Second-line	CCA, GBC	50	N/A	Pembrolizumab plus lenvatinib	N/A	PD-1, TKI	ORR, DCR, PFS	Recruiting
	NCT02443324	1	Second- or later-line	CCA, GBC	298	N/A	Pembrolizumab plus ramucirumab	N/A	PD-1, VEGFR-2 PD-1,	Safety, Tolerability	Completed
	NCT05174650	2	Second- or later-line	ICC	37	N/A	Atezolizumab plus derazantinib	N/A	FGFR1/2/3	ORR	Recruiting
	NCT04298021	2	Second- or later-line	CCA, GBC	74	Non-Randomized	Durvalumab plus AZD6738	AZD6738 + Olaparib	PD-L1, ATR/ATM, PARP	DCR	Recruiting
	NCT03475953	1/2	Second- or later-line	CCA, GBC	482	Non-Randomized	Avelumab plus regorafenib	N/A	PD-L1, TKI	RP2D, ORR	Recruiting
	NCT04550624	2	Second- or later-line	CCA, GBC	40	N/A	Pembrolizumab plus lenvatinib	N/A	PD-2, TKI	ORR	Recruiting
	NCT04298008	2	Third-line	CCA, GBC	26	N/A	Durvalumab + AZD6738	N/A	PD-L1, ATR/ATM	DCR	Recruiting
	NCT05010681	2	N/A	ICC	25	N/A	Sintilimab plus lenvatinib	N/A	PD-1, TKI	ORR	Recruiting
	NCT03639935	2	Maintenance after first line platinum-based systemic chemo-therapy	CCA, GBC	35	N/A	Nivolumab plus rucaparib	N/A	PD-1, PARP	Proportion of patients alive and without radiological or clinical progression at 4 months	Recruiting
ICIs + Chemotherapy+ Target therapy	NCT04300959	2	First-line	CCA, GBC	80	Randomized	Sintilimab plus anlotinib plus GC	N/A	PD-1, PDGFR, FGFR, VEGFR and c-KIT kinase	12 months OS rate	Recruiting
	NCT05342194	3	First-line	ICC	480	Randomized	Toripalimab plus lenvatinib plus GEMOX/GC	Placebo plus GEMOX/GC	PD-1, TKI	OS	Not yet recruiting
	NCT03951597	2	First-line	ICC	30	N/A	JS001 plus Lenvatinib plus GEMOX	N/A	PD-1, TKI	ORR	Active, not recruiting
	NCT05211323	2	First-line	ICC	88	Randomized	Atezolizumab plus bevacizumab plus GC	GC	PD-1, VEGFR	PFS	Recruiting
	NCT04506281	2	NAT	ICC	128	Randomized	Toripalimab plus lenvatinib plus GEMOX	Capecitabine	PD-1, TKI	Event-free survival	Recruiting
ICIs + other therapy	NCT03937895	1/2a	First-line	CCA, GBC	40	N/A	Pembrolizumab plus allogeneic natural killer cell	N/A	PD-1	Safety, Tolerability, ORR	Completed
	NCT04866836	2	Second	CCA, GBC	20	N/A	Tislelizumab plus radiotherapy	N/A	PD-1	ORR	Recruiting
	NCT04068194	1/2	Second- or later-line	CCA, GBC	39	Randomized	Avelumab plus peposertib plus hypofractionated RT	Avelumab plus hypofractionated RT	PD-L1, DNA-PK	Safety, Tolerability, ORR	Recruiting
	NCT05010668	2	Second- or later-line	ICC	25	N/A	Sintilimab plus lenvatinib plus cryoablation	N/A	PD-1,TKI	ORR	Recruiting
	NCT04299581	2	Second- or later-line	ICC	25	N/A	Camrelizumab plus cryoablation	N/A	PD-1	ORR	Recruiting
CAR-T	NCT03633773	1/2	N/A	ICC	9	N/A	MUC-1 CART plus fludarabine plus cyclophosphamide	N/A	MUC-1	DCR	Recruiting
	NCT04951141	1	Second- or later-line	CCA	10	N/A	anti-GPC3 CAR-T	N/A	GPC3	Safety	Recruiting
	NCT05194735	1/2	Second- or later-line	CCA	180	Non-randomized	TCR-T-cell drug product	TCR-T-cell drug product plus IL-2	Neoantigens	Safety-ORR	Recruiting
Cancer vaccines	NCT04853017	1	AT	CCA, GBC	18	N/A	ELI-002 2P Amph-CpG-7909 admixed with Amph modified KRAS peptides	N/A	KRAS	MTD, Safety	Recruiting
Cancer vaccines	NCT03942328	1	N/A	CCA	26	N/A	EBRT, autologous DCs, pneumococcal 13-valent conjugate vaccine	N/A	Dendritic cells	Safety	Recruiting

CCA, cholangiocarcinoma; BTC, biliary tract cancer; GBC, gallbladder cancer; PD-1, programmed cell death protein 1; PD-L1, programmed cell death ligand 1; CTLA-4, cytotoxic T-lymphocyte-associated antigen-4; LAG-3, lymphocyte-activation gene 3; DCR, disease control rate; 5-FU, 5-fluorouracil; GC, gemcitabine and cisplatin; GEMOX, gemcitabine and oxaliplatin; GS, gemcitabine and S-1; MTD, highest dose level for which >33% of subjects had a dose-limiting toxicity; N/A, not available; AT, adjuvant therapy; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; RFS, recurrence-free survival; RP2D, recommended phase 2 dose; RT, radiotherapy.