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Table 2 Key trials of combination immunotherapy in esophagogastric cancers

From: Combination regimens with PD-1/PD-L1 immune checkpoint inhibitors for gastrointestinal malignancies

Study/trial identifier Tumor type Phase Participants Combination intervention Combination regimen type Clinical endpoints TRAEs Reference
CheckMate-032; NCT01928394 Metastatic esophagogastric cancer Ph-1/2 160 Nivolumab 3 mg/kg; nivolumab 1 mg/kg + ipilimumab 3 mg/kg; nivolumab 3 mg/kg + ipilimumab 1 mg/kg PD-1 + CTLA-4 ORR: 12%, 24%, 8%; PFS rate at 12 months: 8%, 17%, 10%; OS rate at 12 months: 39%, 35%, 24% Grade 3/4: 17%, 47%, 27% 2018 JCO; [98]
KEYNOTE-059 cohort 2; NCT02335411 Advanced gastric cancer Ph-2 25 Pembrolizumab + 5-fluorouracil + cisplatin PD-1 + Chemo ORR: 60%; mPFS: 6.6 months; mOS: 13.8 months Grade 3/4: 76% 2017 ASCO; [99]
NCT02999295 Advanced gastric adenocarcinoma Ph-1/2 46 Ramucirumab + nivolumab PD-1 + Target PR: 22%; DCR: 59% Any grade: 87%; Grade 3/4: 13% 2018 ASCO; [100]
NCT02013154 Advanced gastroesophageal cancer Ph-1 13 Dickkopf-1 + pembrolizumab PD-1 + Molecules PR: 1 pt/9 pts; SD: 5 pts/9 pts; DCR at 6 weeks: 75% Grade ≥ 3: 4 pts./9 pts 2018 ESMO; [101]
Attraction-04; NCT02746796 Unresectable advanced or recurrent G/GEJ cancer Ph-2/3 40 Nivolumab + oxaliplatin + S-1,or capecitabine; placebo + oxaliplatin + S-1, or capecitabine PD-1 + Chemo ORR: 68.4%; DCR: 86.8%; Grade 3/4: 57.5% 2018 ESMO; [102]
NCT02689284 Advanced HER2+ gastric adenocarcinoma Ph-1/2 60 Margetuximab + Pembrolizumab PD-1 + Target ORR: 21.6%; DCR: 55%; mOS: 15.6 months Grade ≥ 3: 16.7% 2018 ESMO; [103]
NCT02864381 Unresectable or recurrent gastric or gastroesophageal junction adenocarcinoma Ph-2 144 Andecaliximab 800 mg + nivolumab 3 mg/kg, or nivolumab 3 mg/kg alone PD-1 + Molecules ORR: ADX + nivo, 11.1%; nivo alone, 6.9%; mPFS: ADX + nivo, 1.8 months; nivo alone, 1.9 months; mOS: ADX + nivo, 7.2 months; nivo alone, 5.9 months AEs leading to treatment discontinuation: ADX + NIVO, 1 pt.; nivo, 1 pt 2019 ASCO; [104]
NCT02954536 HER2-positive metastatic esophagogastric adenocarcinoma Ph-2 24 Pembrolizumab + chemotherapy/trastuzumab PD-1 + Chemo/Target ORR: 83%; mPFS: 11.4 months Gr 2 fatigue (35%), Gr 2/3 nausea (35%), Gr 2 diarrhea (26%), Gr2 AST/ALT elevation (16%), Gr2 neutropenia (16%) 2019 ASCO; [105]
NCT02689284 Advanced HER2+ (IHC3+) gastric carcinoma Ph-1/2 66 Margetuximab 15 mg/kg + pembrolizumab 200 mg PD-1 + Target ORR: 41.4%; DCR: 72.4%; mPFS: 5.5 months Grade ≥ 3: 18.2% 2019 ASCO; [106]
NivoRam study; NCT02999295 Advanced gastric adenocarcinoma Ph-1/2 46 Nivolumab 3 mg/kg, Q2W + ramucirumab 8 mg/kg, Q2W PD-1 + Target ORR: 26.7%; PFS rate at 6 months: 37.4%; mPFS: 2.9 months; mOS: 9.0 months Grade 3/4: hypertension, diarrhea, perforation at jejunum, hemorrhage, colitis, pancreatitis, liver dysfunction, cholangitis, hematoma, neutropenia and proteinuria 2019 ASCO; [107]