Table 2

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.