Table 3.
Clinical trials of immune checkpoint inhibitors combined with targeted therapy for advanced gastric cancer.
| Target | Trial (reference) | Therapy line | Phase | Study design | Patient | Main finding | |||
|---|---|---|---|---|---|---|---|---|---|
| mOS (month) | mPFS (month) | ORR (%) | ≥3TRAEs (%) | ||||||
| PD-1 HER2 |
NCT02954536 (47) | 1 | II | Pembrolizumab+trastuzumab+FP/CAPOX | HER2-positive esophagogastric cancer | 27.3 | 13 | 91 | 57 |
| PANTHERA (48, 49) | 1 | I;b/II | Pembrolizumab+trastuzumab+XP | HER2-positive GC | 19.3 | 8.6 | 76.7 | 74.7 | |
| KEYNOTE-811 (50) | 1 | III | Pembrolizumab+trastuzumab+FP/CAPOX vs. placebo+trastuzumab+FP/CAPOX | HER2-positive G/GEJA | NA | NA | 74.4 vs. 51.9 | 57.1 vs. 57.4 | |
| CP-MGAH22–05 (51) | ≥2 | I;b/II | Pembrolizumab+margetuximab | HER2-positive, gastroesophageal adenocarcinoma | 12.5 | 2.7 | 18.48 | 20 | |
| PD-1 LAG-3 HER2 |
MAHOGANY (52) | 1 | II/III | Retifanlimab+margetuximab; trastuzumab+CAPOX/FOLFOX-6 vs. margetuximab ± tebotelimab/retifanlimab+CAPOX/FOLFOX-6 | HER2-positive G/GEJA or esophageal adenocarcinoma | NA | NA | NA | NA |
| CTLA-4 PD-L1 HER2 |
NCT04040699 (53) | 1 | I;b | KN026+KN046 | HER2-positive G/GEJC | NA | NA | 86 | NA |
| PD-1 VEGFR2 |
NCT02443324 (55) | 1 | I;a/b | Ramucirumab+pembrolizumab | GC/GEJC | 14.6 | 5.6 | 25 | 64 |
| PD-1 VEGF |
EPOC1706 (56) | 1/2 | II | Pembrolizumab+lenvatinib | G/GEJA | NR | 7.1 | 69 | 48 |
| PD-1 VEGFR2 |
REGONIVO (57) | ≥3 | I;b | Nivolumab+regorafenib | GC | 12.3 | 5.6 | 44 | 40 (all) |
| UMIN000025947 (58) | 2 | I;/II | Nivolumab+paclitaxel+ramucirumab | GC/GA | 13.1 | 5.1 | 37.2 | 90.7 | |
| NCT03463876 (59) | ≥2 | I;a/b | SHR-1210+apatinib | GC/GEJC | 11.4 | 2.9 | 16 | 60 (all) | |
| NCT04345783 (60) | 2 | II | Camrelizumab (SHR1210)+apatinib+S-1 | G/GEJA | NR | 6.5 | 29.2 | 25 | |
| NCT03472365 (61) | 1 | II | Camrelizumab+CAPOX; camrelizumab+apatinib | VEGFR2-negative G/GEJA | 14.9 | 6.8 | 58.3 | 68.8 | |
| PD-L1 VEGFR2 |
NCT02572687 (62) | ≥2 | I;a/b | Durvalumab+ramucirumab | G/GEJA | 12.4 | 2.6 | 21 | 32.1 |
PD-1, programmed death 1; HER2, human epidermal growth factor receptor 2; FP, 5-fluorouracil+cisplatin; CAPOX, capecitabine+xaliplatin; XP, capecitabine+cisplatin; GC, gastric cancer; G/GEJA, gastric or gastrooesophageal junction adenocarcinoma; FOLFOX-6, oxaliplatin+5-fluorouracil+leucovorin; VEGFR2, vascular epidermal growth factor receptor; GC/GEJC, gastric cancer/gastroesophageal junction cancer; VEGF, vascular epidermal growth factor; GA, gastric adenocarcinoma; S-1, tegafur–gimeracil–oteracil; CAPOX, capecitabine+oxaliplatin; NR, not reached; NA, not applicable.