Main ongoing trials with immune checkpoint inhibitors in gastric, GEJ and esophageal cancers
Target | Agent | Phase | Setting (treatment line) | Treatment | Main objectives | Biomarker | NCT identifier |
PD-1 (±other agents) | Pembrolizumab | Ib | Refractory PD-L1 +solid tumors | Pembrolizumab | ORR=30% | PD-L1 ≥1% | NCT02054806 (KEYNOTE-028) |
III | Second line | Pembrolizumab versus SOC | mOS=8.2 vs 7.1 months. In PD-L1-positive: mOS=9.3 vs 6.7 months | PD-L1 (CPS ≥10%) | NCT03933449 (KEYNOTE-181) | ||
III | First line | Pembrolizumab+chemotherapy versus placebo +chemotherapy | Ongoing | PD-L1 (CPS ≥10%) | NCT03189719 (KEYNOTE-590) | ||
II | Cohort 1: refractory Cohort 2: first line Cohort 3: first line PD-L1+ | Cohort 1: pembrolizumab monotherapy Cohort 2: pembrolizumab +chemotherapy Cohort: Pembrolizumab monotherapy | Ongoing | PD-L1 | NCT02335411 (KEYNOTE-059) | ||
III | Second line | Pembrolizumab versus paclitaxel | Ongoing | PD-L1 positive | NCT02370498 (KEYNOTE-061) | ||
III | First line | Pembrolizumab or pembrolizumab +chemotherapy or placebo plus chemotherapy | Ongoing | PD-L1 positive | NCT02494583 (KEYNOTE-062) | ||
III | Neoadjuvant/adjuvant | Pembrolizumab+chemotherapy versus placebo +chemotherapy | Ongoing | NA | NCT03221426 (KEYNOTE-585) | ||
III | First line, HER2+ | Pembrolizumab+Trastuzumab + Chemotherapy versus Placebo+Trastuzumab + Chemotherapy | Ongoing | NA | NCT03615326 (KEYNOTE-811) | ||
Nivolumab | III | Refractory | Nivolumab versus placebo | mOS=5.26 vs 4.14 months 12 month OS=26.2% vs 10.9% | NA | NCT02267343 (ATTRACTION-2) | |
III | Refractory | Nivolumab versus chemotherapy | median OS=10.9 vs 8.4 months | PD-L1 | NCT02569242 (ATTRACTION-3) | ||
II/III | First line | Nivolumab +chemotherapy (Nivolumab+SOX vs Nivolumab+CapeOX) | ORR=57.1% with nivolumab plus SOX vs 76.5% with nivolumab plus CapeOX. mPFS=9.7 months vs 10.6 months | PD-L1 | NCT02746796 (ATTRACTION-4) | ||
I/II | Refractory | Nivolumab versus Nivolumab+Ipilimumab | ORR=12% with Nivolumab; vs 24% with Nivo 1+Ipi 3; vs 8% with Nivo 3+Ipi 1 | NA | NCT01928394 (CHECKMATE 032) | ||
III | First line | Nivolumab+Ipilimumab or Nivolumab+chemotherapy versus chemotherapy | Ongoing | PD-L1 | NCT02872116 | ||
III | Adjuvant, resected Esophageal and GEJ cancers | Nivolumab versus placebo | Ongoing | NA | NCT02743494 (CHECKMATE 577) | ||
III | First line | O | PD-L1 ≥1% | NCT03143153 (CHECKMATE 648) | |||
PD-L1 (±other agents) | Durvalumab | II | Localized unresectable Esophageal cancer | Durvalumab+chemoradiotherapy followed by durvalumab maintenance | Ongoing | NA | NCT03777813 |
Avelumab | I | Refractory | Avelumab | NA | NA | NCT01772004 | |
III | Third line, refractory | Avelumab versus chemotherapy | ORR=2.2% vs 4.3%; mOS=4.6 vs 5 months | PD-L1 | NCT02625623 (JAVELIN 300) | ||
III | Maintenance, after first line | Avelumab versus chemotherapy | Ongoing | NA | NCT02625610 (JAVELIN 100) Gastric and GEJ | ||
II | Neoadjuvant | Avelumab+chemotherapy | Ongoing | NA | NCT03288350 |
CPS, Combined Positive Score; GEJ, gastroesophageal junction; mOS, median overall survival; mPFS, median progression-free survival; NA, not available; NCT, national clinical trial; ORR, objective response rate; PD-1, programmed cell death-1; PD-L1, programmed cell death ligand-1; SOC, standard of care; SOX, S-1 (tegafur, gimeracil, and oteracil potassium) plus oxaliplatin.