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 3Â mg/kg; nivolumab 1Â mg/kg + ipilimumab 3Â mg/kg; nivolumab 3Â mg/kg + ipilimumab 1Â mg/kg | PD-1 + CTLA-4 | ORR: 12%, 24%, 8%; PFS rate at 12Â months: 8%, 17%, 10%; OS rate at 12Â 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: 6.6Â months; mOS: 13.8Â 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: 11.4Â 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] |