Copyright ©The Author(s) 2018.
World J Gastroenterol. Aug 28, 2018; 24(32): 3583-3616
Published online Aug 28, 2018. doi: 10.3748/wjg.v24.i32.3583
Table 1 Clinical trials using CTLA-4 and PD/PD-L1 checkpoint inhibitors
Checkpoint inhibitorsStudy numberPhaseStatusStudy designStudy populationPrimary outcome measuresSecondary outcome measuresNo. of patients (estimated enrollment)Final results
Nivolumab, IpilimumabNCT03342417IIRecruitingNIVO + IPI-Neoadjuvant breast cancer -Platinum-resistant advanced ovarian/GC- % AE- DOR, OS, QOL, recurrence rate60Pending
Nivolumab, IpilimumabNCT02872116 (CHECKMATE-649)IIIRecruiting- NIVO + IPI/ -NIVO + chemo vs chemotherapy (XELOX/FOLFOX)-Naive advanced/metastatic GC/GEJ-OS NIVO + IPI vs chemo (PD-L1 + tumors) -OS NIVO + chemo vs chemo -ORR, PFS nivo + chemo vs chemo-OS NIVO + IPI vs chemo -PFS NIVO + IPI/ NIVO + chemo vs chemo (PD-L1+) -ORR NIVO + chemo vs chemo1349Pending
Nivolumab, IpilimumabNCT02935634 (FRACTION-GC)IIRecruiting- NIVO + IPI -NIVO + RELATLIMAB -NIVO + BMS-986205-Advanced GC-ORR, DOR, PFS-% AE, SAE, discontinuation/death due to treatment300Pending
Nivolumab, IpilimumabNCT03044613IbRecruiting- NIVO/NIVO + IPI prior to chemoradiation + NIVO-Neoadjuvant treatment, resectable stage II/III EC/GEJ-% AE-Feasibility of induction treatment -Path CR -Quantity of NIVO bound to PD1 receptor -Changes in expression of immune markers -OS, RFS32Pending
Nivolumab, IpilimumabNCT03443856 (VESTIGE)IINot yet recruiting- NIVO + IPI-Adjuvant treatment GC/GEJ adenocarcinoma stage Ib-IVa, ↑risk of recurrence (ypN1-3 + /R1) after neoadjuvant treatment + resection-DFS-OS -Relapse rate -Loco-regional/distant failure rates -% AE, QOL, global health status240N/A
Nivolumab, IpilimumabNCT03409848 (INTEGA)IIRecruiting-IPI/FOLFOX + NIVO and TRAS-Advanced/metastatic GC adenocarcinoma, previously untreated-OS-% AE -PFS, RR, QOL -Translational research -Central imaging review97Pending
Nivolumab, IpilimumabNCT02834013IIRecruiting-NIVO + IPI-Rare tumors, including gastric NET, SqCC, GIST-ORR-RECIST-Toxicities -OS, PFS -Clinical benefit rate -ir-ORR/PFS707Pending
Nivolumab, IpilimumabNCT03126110I/IIRecruiting-NIVO + INCAGN01876 -IPI + INCAGN01876 -NIVO + IPI + INCAGN01876-Advanced/metastatic malignancies, including GC-Toxicities (%AE) -ORR-RECIST-DR, DDC, PFS, OS- RECIST450Pending
Nivolumab, IpilimumabNCT03241173I/IIrecruiting-NIVO + INCAGN0949 -IPI + INCAGN0949 -NIVO + IPI + INCAGN0949-Advanced/ metastatic malignancies, including GC-Toxicities (%AE) -ORR-RECIST-DR, DDC, PFS, OS- RECIST651Pending
IpilimumabNCT01585987IICompleted-IPI vs BSC (5-FU)-Unresectable/ metastatic GC/GEJ adenocarcinoma (following Ist line treatment)-ir-PFS (ir RECIST) -% BOR-PFS (mWHO) -OS143-ir-PFS ↓ (2.92 vs 4.89 mo); -mWHO-PFS↓ (2.72 vs 4.89) (P = 0.03); -OS at study completion 12.68 vs 12.06 mo
Tremelimumab, DurvalumabNCT02658214IRecruiting-TREME + DURVA + chemo (platinum-based SOC)-Ist line locally advanced/ metastatic solid tumor, including GC/GEJ-Laboratory findings -%AE, safety, tolerability -Tumor assessment (RECIST)-42Pending
NivolumabNCT03453164 (CIRCUIT)I/IIRecruitingNIVO + radiotherapy-Unresectable recurrent GC (3 rd line)-DCR: -PD: on CT/ MRI/ PET-CT -CR/PR/SD-Mean survival -% AE -Local control rate -% PL-L1+, MHCI- tumor cells -Cytokines serum concentration -% regT cells -% Ag-specific CTL40Pending
NivolumabNCT02267343IIIActive, not recruitingNIVO vs placebo-Refractory, unresectable, advanced/ recurrent GC/GEJ-OS, PFS-ORR, DOR, %AE, %SAE, safety480Pending
NivolumabNCT02746796II/IIIRecruitingNIVO + chemo-Ist line therapy, unresectable advanced/ recurrent GC/GEJ-PFS -OS-ORR, DOR, DCR -TTR, BOR -% AE, SAE, laboratory abnormalities680Pending
NivolumabNCT03006705IIIRecruitingNIVO + chemo vs placebo + chemo-Adjuvant treatment p stage III GC/GEJ (after D2 resection)-RFS-OS -Safety- % AE, SAE, laboratory abnormalities700Pending
NivolumabNCT02999295I/IIRecruiting-NIVO + RAMUCIRUMAB-Advanced/ recurrent unresectable GC/GEJ-No. of pts with DLT -6 mo PFS-%AE -ORR -DCR -OS, PFS44Pending
NivolumabNCT02946671IRecruiting-NIVO + MOGAMULIMUMAB (KW-0761 = anti-CCR4)-Preoperator treatment against solid cancers, including GC-% AE - FOXp3 + tumors by immunohistochemistry-ORR-RECIST -% ↓Treg18Pending
NivolumabNCT02951091 (Biomarker – integrated Umbrella)ObservationalRecruiting-NIVO/ AFATINIB/ GSK2636771 + PACLITAXEL-Advanced GC -Different molecular cohorts: PD-L1+, MSI-H, EBV+ → NIVO-PFS-400Pending
NivolumabNCT02465060 (The MATCH screening trial)IIRecruiting-NIVO/ other agents (according to genetic testing)-Advanced/ metastatic solid tumors (including GC), lymphomas, multiple myelomas → mismatch repair deficiency (loss of MLH1/ MLH2)-ORR-OS, PFS -TTP6452Pending
NivolumabNCT02862535IbActive, non-recruiting-ANDECALIXIMAB (GS-5745) ± NIVO/chemo-Previously treated, advanced GC/GEJ adenocarcinoma (Japan)-Safety (% AE)- Serum concentration of Andecaliximab -% Ab-anti Andecaliximab36N/A
PembrolizumabNCT03382600 (MK-3475-659/ KEYNOTE 659)IIRecruiting-PEMBRO + OXALIPLATIN + TS-1 vs -PEMBRO + CISPLATIN + TS-1-Advanced CG/GEJ adenocarcinoma, HER2(-), PD-L1+-ORR-RECIST-ORR (i-RECIST) -DCR, DOR, TTR, PFS (RECIST, iRECIST) -OS, % AE90Pending
PembrolizumabNCT02901301I/IIRecruiting-PEMBRO + TRASTUZUMAB + chemo-Ist line advanced, GC HER2+-Recommended dose -ORR-RECIST-DOR -TTR49Pending
PembrolizumabNCT03342937IIRecruitingPEMBRO + XELOX-Ist line metastatic GC adenocarcinoma-PFS-OS - % AE50Pending
PembrolizumabNCT02918161IIRecruitingPEMBRO + chemo (SOC)-Perioperative setting GC/GEJ-2 years DFS- Pathol CR -OS, ORR (RECIST) -DFS40Pending
PembrolizumabNCT02689284I/IIRecruitingPEMBRO + MARGETUXIMAB-HER2 + advanced, metastatic GC/GEJ- Expansion phase dose of Margetuximab -Antitumor activity: RD, ORR (RECIST, ir-RECIST)-OS -PFS72Pending
PembrolizumabNCT03257163IIRecruiting-PEMBRO + CAPECITABINE + radiotherapy (perioperative)-Mismatch repair deficient, EBV+, operable GC-RFS-40Pending
PembrolizumabNCT03064490 (PROCEED)IIRecruiting-PEMBRO + chemoradiotherapy-Neoadjuvant treatment, locally advanced EG cancers-Pathol CR-Toxicity (% AE)38Pending
PembrolizumabNCT02563548IbRecruiting-PEMBRO + PEGPH2O (Pegylated Recombinant Human Hyaluronidase)-Hyaluronan-high (HA-H) patients with relapsed/ refractory cancers (adenocarcinoma)-ORR-DCR, DOR, PFS (RECIST, ir-RECIST)81Pending
PembrolizumabNCT02954536IIRecruiting-PEMBRO+TRASTUZUMAB+chemo-Advanced, metastatic HER2+, EG (Ist line)-PFS (RECIST)-37Pending
PembrolizumabNCT03221426 (MK-3475-585) (KEYNOTE-585)IIIRecruiting-PEMBRO + cemo vs placebo + chemo-Neoadjuvant/adjuvant previously untreated GC/GEJ adenocarcinoma-OS - EFS event-free survival) -Pathol CR -% AE + discontinuation of treatment-DFS860Pending
PembrolizumabNCT03196232IIRecruiting-PEMBRO + EPACADOSTAT-Metastatic/ unresectable GEJ-6-mo PFS-ORR (RECIST) -OS -RR30Pending
PembrolizumabNCT03019588 (MK-3475-063/ KEYNOTE-063)IIIRecruiting-PEMBRO vs chemo (PACLITAXEL)-Progression after Ist line platinum-fluoropyridine chemo, advanced GC/GEJ adenocarcinoma, PD-L1+ (Asia)-OS, PFS (RECIST)-ORR-RECIST -% AE, % discontinuation due to AE360Pending
PembrolizumabNCT03488667IINot yet recruitingPEMBRO + mFOLFOX-Neoadjuvant treatment GEJ adenocarcinoma -adjuvant treatment GC-yp RR (pathologic response) -toxicity (% AE)-ORR, DFS, OS -PET scan response rate - % PD-L1 + in tumor cells40N/A
PembrolizumabNCT03413397IIRecruitingPEMBRO + LENVATINIB MESYLATE-Metastatic/ recurrent GC/GEJ-ORR-RECIST-PFS, OS -Characteristic immunologic changes29Pending
PembrolizumabNCT02730546I/IIRecruitingPEMBRO + chemoradiotherapy-Locally advanced, operable, GEJ/gastric cardia adenocarcinoma (neoadjuvant setting)-Path CR -PFS-R0 resection, DSF -Dose-limiting AE, % surgical complications, OS, PFS, time to relapse68Pending
PembrolizumabNCT02318901Ib/IIActive, not recruitingPEMBRO-TRASTUZUMAB/ADO-TRASTUZUMAB-ETAMSINE/CETUXIMAB-Unresectable HER2+, advanced GC/GEJ-Dose of mAb combined with PEMBRO-% grade 3-4 AE -RR (RECIST, ir-RECIST) -OS, PFS -Circulating tumor DNA -Imaging changes90N/A
PembrolizumabNCT03095781IRecruitingPEMBRO + XL888 (= Hsp90 inhibitor)-Advanced gastrointestinal cancer (including GC)-Recommended dose for combined treatment-ORR, PFS, RS (RECIST) -OS50Pending
PembrolizumabNCT02346955ITerminated-CM-24[MK-6018 = mAb against CEACAM1] ± PEMBRO-Advanced/recurrent malignancies (including GC)-% AE, discontinuation due to AE, DLT-Maximum drug concentration, half-life elimination, ORR, DOR27Pending
PembrolizumabNCT02178722 (KEYNOTE-037/ECHO-202)I/IIRecruiting-PEMBRO + EPACADOSTAT-Selected carcinomas (including GC)-% DTL -ORR-PFS -% AE -OS508Pending
PembrolizumabNCT02903914I/IIRecruiting-PEMBRO + ARGINASE INHIBITOR INCB001158- Advanced/metastatic solid tumors (including GC)-% AE- Rrecommended dose of arginase Inhibitor ± PEMBRO -Pharmacokinetic profile -Antitumor activity of drugs (RECIST, ir RECIST)346Pending
PembrolizumabNCT03122548IIActive, not recruitingPEMBRO + CRS-207-Recurrent/metastatic GC/EG (1-2 prior lines of systemic treatment)-% AE-Tumor response (RECIST) -OS -Characterization of immune response -Analysis of biomarker expression79N/A
PembrolizumabNCT02393248I/IIRecruiting-INCB054828 + PEMBRO/ chemo/ TRASTUZUMAB-Advanced malignancies (including GC), progression after prior treatment-Maximum tolerated dose, pharmacodynamic of INCB054828-ORR -Maximum/minimum plasma Concentration of NCB054828280Pending
PembrolizumabNCT02494583IIIActive, not recruiting-PEMBRO vs -PEMBRO + chemo vs -Placebo + chemo-Ist line treatment, advanced GC/GEJ-PFS (RECIST) -OS-ORR, DOR (RECIST) -QOL764N/A
PembrolizumabNCT02370498 (KEYNOTE-061)IIIActive, not recruiting-PEMBRO vs chemo (PACLITAXEL)-Advanced GC/GEJ adenocarcinoma, Progressed after Ist line (platinum + fluoropyrimidine), PD-L1+-PFS, OS- in PD-L1+-PFS, OS -TTP, ORR592Pending
PembrolizumabNCT02335411 (KEYNOTE-059)IIActive, not recruiting-PEMBRO or PEMBRO + chemo (CISPLATIN + 5-FU/CAPECITABINE)-Recurrent/metastatic GC/GEJ adenocarcinoma-% AE, discontinuation of treatment due to AE -ORR-316Pending
PembrolizumabNCT03277352I/IIRecruiting-INCAGN01876 + PEMBRO + EPACADOSTAT-Advanced/ metastatic malignancies-% AE -ORR, CRR (RECIST)-ORR, DCR, DOR, PFS, OS (rECIST, mRECIST)166Pending
PembrolizumabNCT02443324IActive, not recruiting-PEMBRO + RAMUCIRUMAB-GC/GEJ (NSCLC, transitional urothelial cancer, biliary tract cancer)-DTL-% BOR of CR/PR, ORR -% SD -DOR, time to response -PFS, OS -Pharmacokinetics155Pending
AvelumabNCT02625623 (JAVELIN GASTRIC 300)IIIActive, not recruiting-AVE + BSC vs -chemo+BSC/BSC-Unresectable, recurrent, locally advanced/ metastatic GC/GEJ adenocarcinoma (3rd line)-OS-PFS, BOR -QOL37Pending
AvelumabNCT03399071 (ICONIC)IIRecruiting-AVE + chemo (FLOT)-Perioperative setting, operable EC/GC-Pathol CR-% grade 3-4 AE -Radiologic response (RECIST) -median PFS, OS40Pending
AvelumabNCT02625610 (JAVELIN GASTRIC 100)IIIActive, not recruiting-AVE maintenance vs Ist line continuation of chemo (OXALIPLATIN + FLUOROPYRIMIDINE)-Unresectable, locally advanced/ metastatic GC/GEJ adenocarcinoma-OS, PFS-BOR (RECIST) -QOL -% AE499Pending
AvelumabNCT01943461 (JAVELIN SOLID TUMOR JPN)IActive, not recruiting-AVE-Locally advanced/ metastatic solid tumors (Japan) → expansion part GC patients (Asia)-DLT-Concentration assessment, elimination half-life -% PD-L1 -BOR+ irBOR, PFS +irPFS -OS % Ab-anti AVE -% AE57Pending
AvelumabNCT03475953 (REGOMUNE)I/IINot yet recruiting-AVE + REGORAFENIB-Advanced/metastatic digestive solid tumors (including GC)-Recommended doses -Assessment of Regorafenib antitumor activity -Pharmacokinetics-Maximum tolerated dose -DLT -% AE -BOR, ORR, PFS, OS -Blood/tumor growth biomarkers212Pending
AvelumabNCT02554812 (JAVELINE Medley)Ib/IIRecruiting-AVE + other immunotherapies → AVE + PD 0360324 (M-CSF mAb) (gastric cancer)-Locally advanced/ metastatic solid tumors (including GC)-% DLT -ORR-Serum concentration of drugs -Ab-anti drugs -TTR, DOR, PFS, OS -Tumor biomarkers (PD-L1, CD8+T cells)560Pending
DurvalumabNCT02734004 (MEDIOLA)I/IIActive, not recruiting-DURVA + OLAPARIB (PARP inhibitor)-Advanced solid tumors (including GC)-DCR (at CT/MRI) -% AE -Safety- vital signs, blood samples-% PD-L1 -DCR (mRECIST) -Time to treatment discontinuation) -OS -% change in tumor size (CT/MRI) -Serum concentration of Ab-anti drug -Pharmacokinetics -ORR, DOR, PFS (mRECIST)148Pending
DurvalumabNCT02572687IActive, not recruitingDURVA + RAMUCIRUMAB-Locally advanced unresectable/ metastatic gastrointestinal (including GC/GEJ adenocarcinoma) and thoracic malignancies-% DLT-ORR, DCR -DOR, TTR -PFS -OS -Pharmacokinetics -% Ab-anti drug114Pending
DurvalumabNCT02678182 (PLATFORM)IIRecruiting-DURVA vs. CAPECITABINE vs. TRASTUZUMAB vs. RUCAPARIB vs. surveillance-Maintenance treatment, locally advanced/ metastatic HER2+/-EG, adenocarcinoma (after Ist line chemo)-PFS (RECIST)-PFR -OS, ORR (RECIST) -% AE -PFS, PFR, OS, ORR according to PD-L1 immunohistochemical status770Pending
DurvalumabNCT02264678I/IIRecruiting-AZD6738 ± Chemo/OLAPARIB/DURVA-Advanced malignancies (including GC)-Safety, tolerability (AE, SAE)-Pharmacodynamics, biomarker changes -Serum concentration of drug, half-life, etc. -BOR, ORR, % change in tumor size250Pending