Table 1.
Representative clinical trials investigating immunotherapies in gastric and gastroesophageal cancers
| Compound | Target or combo | Phase | GC setting | Primary endpoint | Clinical trial ID |
|---|---|---|---|---|---|
| PD-1 monotherapy | |||||
| JS001 | PD-1 | Ib/II | >1 prior line | ORR | NCT02915432 |
| Pembrolizumab | PD-1 | I/II | Neoadj | pCR, PFS | NCT02730546 |
| Pembrolizumab (KEYNOTE-059) | PD-1 | II | First-line (cohort 3) | ORR, AEs | NCT02335411 |
| Pembrolizumab (KEYNOTE-061) | PD-1 | III | Second-line | OS, PFS in PD-L1+ | NCT02370498 |
| Pembrolizumab (KEYNOTE-062) | PD-1 | III | First-line (arm 1) | PFS, OS | NCT02494583 |
| Nivolumab | PD-1 | III | >2 prior lines | OS | NCT02267343 |
| PD-L1 monotherapy | |||||
| Avelumab (JAVELIN gastric 100) | PD-L1 | III | First-line maintenance | OS | NCT02625610 |
| Avelumab (JAVELIN gastric 300) | PD-L1 | III | Third-line | OS | NCT02625623 |
| Atezolizumab | PD-L1 | I | No limits | DLTs | NCT01375842 |
| Durvalumab (PLATFORM) | PD-L1 | II | Maintenance after stage II–III treatment | PFS | NCT02678182 |
| Dual checkpoint inhibitor | |||||
| Nivolumab + ipilimumab (CheckMate-649) | PD-1 + CTLA-4 | III | First-line | OS | NCT02872116 |
| Durvalumab + tremelimumab | PD-L1 + CTLA-4 | I/II | >1 prior line | AEs, ORR, PFS | NCT02340975 |
| Nivolumab + ipilimumab (FRACTION-GC) | PD-1 + CTLA-4 | II | Advanced GC | ORR, DOR, PFS | NCT02935634 |
| Checkpoint inhibitor + cytotoxic therapy | |||||
| Pembrolizumab (KEYNOTE-059) | PD-1 + Cis/5FU | II | First-line (cohort 2) | ORR, AEs | NCT02335411 |
| Pembrolizumab (KEYNOTE-062) | PD-1 + Cis/5FU | III | First-line (arm 2) | PFS, OS | NCT02494583 |
| Pembrolizumab | PD-1 + FOLFOX | I/II | FOLFOX indicated | Safety | NCT02268825 |
| Pembrolizumab | PD-1 + chemo | II | Perioperative | DFS at 24 m | NCT02918162 |
| Pembrolizumab | PD-1 + FOLFOX | II | Perioperative | pCR, AEs | NCT02943603 |
| Nivolumab | PD-1 + SOX or CapOX | II | First-line | ORR | NCT02746796 |
| Pembrolizumab | PD-1 + HER2 + Cis/5FU | I/II | First-line | ORR, RP2D | NCT02901301 |
| Checkpoint + biologic or other combinations | |||||
| Pembrolizumab + radiation | PD-1 + radiation | II | No limits | Biomarkers | NCT02830594 |
| Ramucirumab + pembrolizumab | VEGFR2 + PD-1 | I | 0–2 prior lines | DLTs | NCT02443324 |
| Ramucirumab + durvalumab | PD-L1 + VEGFR2 | I | 1–2 prior lines | DLTs | NCT02572687 |
| Pembrolizumab with trastuzumab and cisplatin/5FU | PD-1 + HER2 + chemo | II | First-line | PFS | NCT02954536 |
| GDC-0919 and atezolizumab | IDO inhibitor and PD-L1 | I | >1 prior line | DLTs, AEs | NCT02471846 |
| Epacadostat and durvalumab | IDO inhibitor + PD-L1 | I/II | >1 prior line | DLTs, ORR | NCT02318277 |
| PLX3397 and pembrolizumab | CSF1R + PD-1 | I/II | >1–2 prior lines | AEs | NCT02452424 |
| Durvalumab and olaparib (MEDIOLA) | PARP + PD-L1 | I/II | >1–2 prior lines | DCR, safety | NCT02734004 |
| PEGPH20 with pembrolizumab | Hyaluronidase and PD-1 | Ib | >1 prior line | DLT, ORR | NCT02563548 |
| GS-5745 and nivolumab | MMP-9 and PD-1 | II | First-line | ORR | NCT02864381 |
Notes: Data are derived from clinicaltrials.gov (accessed 1/2017). Due to space constraints, a complete list is not shown and preference is given to trials focused on GC and GEJ cancers over those accepting all solid tumors. Several trials have multiple arms; please refer to clinicaltrials.gov for further details.
Abbreviations: VEGFR, vascular endothelial growth factor receptor; MMP, matrix metalloproteinase; GC, gastric cancer; DLT, dose limiting toxicity; DCR, disease control rate; AEs, adverse events; RP2D, recommended Phase II dose; DFS, disease-free survival; DOR, duration of response; ORR, overall response rate; PFS, progression-free survival; OS, overall survival; m, months; CSF, colony stimulating factor; chemo, chemotherapy; IDO, indoleamine-2,3-dioxygenase; Neoadj, neoadjuvant; GEJ, gastroesophageal junction; PARP, poly (ADP-ribose) polymerase inhibitor; pCR, pathologic complete response; Cis/5FU, SOX, S-1 and oxaliplatin; CapOX, capecitabine and oxaliplatin.