Table 2:

Ongoing Phase 2 and 3 combination clinical trials with immune checkpoint inhibitors in advanced gastrointestinal cancers

Trial number	Phase	ICI	ICI pathway	Combination therapy	Combination strategy	Cancer type	Patient selection	Status
Enhancing tumor immunogenicity, antigen presentation, and T-cell priming
NCT03190265	2	Nivolumab, ipilimumab	PD1, CTLA-4	GVAX/CRS-207, cyclophosphamide	Cancer vaccine, chemotherapy	Pancreatic cancer	None	Active, recruiting
NCT03836352	2	Pembrolizumab	PD1	DPX-survivac, cyclophosphamide	Cancer vaccine, chemotherapy	Hepatocellular carcinoma, MSI high GI cancers	Survivin expression (not applicable to colorectal and gastric cancers)	Active, recruiting
NCT01896869	2	Ipilimumab	CTLA-4	Allogenic GM-CSF transfected pancreatic tumor vaccine	Cancer vaccine	Pancreatic cancer	Patients must achieve stable disease after 8–12 doses of folfirinox	Active, not recruiting
NCT03806309	2	Nivolumab	PD1	OSE2101	Cancer vaccine	Pancreatic cancer	Patients must achieve stable disease or partial response after 8–12 doses of folfirinox	Active, recruiting
NCT03006302	2	Pembrolizumab	PD1	GVAX/CRS-207, epacadostat, cyclophosphamide	Cancer vaccine, IDO inhibitor, chemotherapy	Pancreatic cancer	None	Active, recruiting
NCT03161379	2	Nivolumab	PD1	GVAX, SBRT, cyclophosphamide	Cancer vaccine, radiotherapy, chemotherapy	Pancreatic cancer	Patients with borderline resectable disease only	Active, recruiting
NCT02648282	2	Pembrolizumab	PD1	GVAX, SBRT, cyclophosphamide	Cancer vaccine, radiotherapy, chemotherapy	Pancreatic cancer	Patients with locally advanced disease only	Active, recruiting
NCT03723915	2	Pembrolizumab	PD1	Reolysin	Oncolytic virus	Pancreatic cancer	None	Active, recruiting
Targeting oncogenic signaling
NCT03201458	2	Atezolizumab	PD1	Cobimetinib	MEK inhibition	Biliary tract cancer	None	Active, not recruiting
NCT02060188	2	Nivolumab, ipilimumab	PD1, CTLA-4	Cobimetinib	MEK inhibition	Colorectal cancer	None	Active, not recruiting
NCT03608046	2	Avelumab	PD1	Cetuximab, irinotecan	Anti-EGFR antibody, chemotherapy	Colorectal Cancer	BRAF wild type, MSS	Active, recruiting
NCT03409848	2	Nivolumab, Ipilimumab	PD1, CTLA-4	Trastuzumab	Anti HER-2 antibody	Gastric cancer and gastroesophageal junction cancer	HER2 positive disease	Active, recruiting
NCT03818997	2	Atezolizumab	PD1	DKN-01, paclitaxel	Wnt pathway inhibition, chemotherapy	Esophageal cancer, gastric cancer, gastroesophageal junction cancer, and biliary tract cancer	None	Not yet recruiting
Targeting tumor microenvironment
NCT03895970	2	Pembrolizumab	PD1	Lenvatinib	Anti-angiogenesis	Hepatocellular carcinoma and biliary tract cancer	None	Active, recruiting
NCT02519348	2	Durvalumab, tremelimumab	PD-L1, CTLA-4	Bevacizumab	Anti-angiogenesis	Hepatocellular carcinoma	None	Active, recruiting
NCT03841201	2	Nivolumab	PD1	Lenvatinib	Anti-angiogenesis	Hepatocellular carcinoma	None	Active, recruiting
NCT03713593	3	Pembrolizumab	PD1	Lenvatinib	Anti-angiogenesis	Hepatocellular carcinoma	None	Active, recruiting
NCT03439891	2	Nivolumab	PD1	Sorafenib	Anti-angiogenesis	Hepatocellular Carcinoma	None	Active, Recruiting
NCT03603756	2	SHR-1210	PD1	Apatinib, irinotecan/paclitaxel/nedaplatin	Anti-angiogenesis, chemotherapy	Esophageal cancer	SCC	Active, recruiting
NCT03951597	2	JS001	PD1	Lenvatinib, gemcitabine, and oxaliplatin	Anti-angiogenesis, chemotherapy	Biliary tract cancer	None	Active, recruiting
NCT03414983	2, 3	Nivolumab	PD1	Bevacizumab, FOLFOX (fluorouracil, leucovorin, and oxaliplatin)	Anti-angiogenesis, chemotherapy	Colorectal Cancer	None	Active, not recruiting
NCT02997228	3	Atezolizumab	PD1	Bevacizumab, FOLFOX (fluorouracil, leucovorin, and oxaliplatin)	Anti-angiogenesis, chemotherapy	Colorectal Cancer	MSI High	Active, Recruiting
NCT03698461	2	Atezolizumab	PD1	Bevacizumab, FOLFOX (fluorouracil, leucovorin, and oxaliplatin)	Anti-angiogenesis, chemotherapy	Colorectal cancer	Patients with potentially resectable liver metastases only	Active, recruiting
NCT02873195	2	Atezolizumab	PD1	Bevacizumab and capecitabine	Anti-angiogenesis, chemotherapy	Colorectal cancer	None	Active, not recruiting
NCT03336216	2	Nivolumab	PD1	Cabiralizumab	CSF1R inhibition	Pancreatic Cancer	None	Active, recruiting
NCT03694977	2	PDR001	PD1	MCS110	CSF1R inhibition	Gastric cancer	None	Active, recruiting
NCT03331562	2	Pembrolizumab	PD1	Paricalcitol	Vitamin D analog	Pancreatic cancer	Patients who achieved stable disease or partial response for a period of 2 months with no further shrinkage of ≥30% on scan on their first-line chemotherapy	Active, recruiting
Overcoming T-cell exhaustion
NCT03642067	2	Nivolumab	PD1	Relatlimab	LAG-3 inhibition	Colorectal Cancer	MSS	Active, Recruiting
NCT02060188	2	Nivolumab, ipilimumab	PD1, CTLA-4	Daratumumab, anti-LAG-3 antibody	CD38 inhibition, LAG3 inhibition	Colorectal cancer	None	Active, not recruiting
NCT03662659	2	Nivolumab	PD1	Relatlimab, XELOX (oxaliplatin, capecitabine)/FOLFOX (fluorouracil, leucovorin, oxaliplatin)/XOS (oxaliplatin, S-1)	LAG3 inhibition, chemotherapy	Gastric cancer and gastroesophageal junction cancer	None	Active, recruiting
NCT03680508	2	TSR-042	PD1	TSR-022	Anti-TIM3 antibody	Hepatocellular carcinoma	None	Not yet recruiting
Epigenetic reprogramming
NCT03250273	2	Nivolumab	PD1	Entinostat	Histone deacetylase inhibitor	Biliary tract cancer, pancreatic cancer	None	Active, recruiting

Trials that combine ICIs with chemotherapy alone were not included in this table. ICI: Immune checkpoint inhibitors, MSI: Microsatellite instability, MSS: Microsatellite stable, GI: Gastrointestinal, CTLA: Cytotoxic T-lymphocyte antigen, IDO: Indoleamine 2, 3-dioxygenase