Targeted therapies in metastatic gastric cancer: Current knowledge and future perspectives

Table 1 Ongoing phase II/III target trials in advanced gastric cancer

Study	Line	Control arm	Experimental arm	Target	NCT number
JACOB	1st	Placebo +	Pertuzumab +	HER2	NCT01774786
		Trastuzumab +	Trastuzumab +
		Chemotherapy	Chemotherapy
ID NUMBER:11-166	2nd	-	Afatinib +	HER2	NCT01522768
			Paclitaxel
NIEGA	2nd	-	Irinotecan +	EGFR	NCT03400592
			Nimotuzumab
ENRICH	2nd	Irinotecan	Irinotecan +	EGFR	NCT01813253
			Nimotuzumab
CheckMate-649	1st	Oxaliplatin +	- Nivolumab + Oxaliplatin +	PD-1, CTLA-4	NCT02872116
			Fluoropyrimidine
		Fluoropyrimidine
			- Ipilimumab + Nivolumab
ATTRACTION-4	1st	Placebo + Oxaliplatin + S-1/Capecitabine	Oxaliplatin + S-1/Capecitabine + Nivolumab	PD-1	NCT02746796
JAVELIN Gastric 100	1st	Maintenance 1st line	Avelumab	PD-L1	NCT02625610
KEYNOTE-062	1st	Platin/fluoropyrimidine	- Pembrolizumab	PD-1	NCT02494583
			- Pembrolizumab + Platin/fluoropyrimidine
SPOTLIGHT	1st	Oxaliplatin +	Zolbetuximab + Oxaliplatin +	CLDN18.2	NCT03504397
		Fluoropyrimidine	Fluoropyrimidine
ILUSTRO	1st/3rd	-	- Zolbetuximab monotherapy, 3rd line	CLDN18.2	NCT03505320
			- Zolbetuximab + FOLFOX, 1st line
GLOW	1st	Oxaliplatin +	Zolbetuximab + Oxaliplatin +	CLDN18.2	NCT03653507
		Capecitabine	Capecitabine
ANGEL	3rd	BSC	Apatinib	VEGFR-2	NCT03042611
INTEGRATE II	3rd	Placebo	Regorafenib	VEGFR1-3,	NCT02773524
				FGFR,
				PDGFR-β RAF, RET and KIT

JACOB: A Study of Pertuzumab in Combination With Trastuzumab and Chemotherapy in Participants With Human Epidermal Growth Factor Receptor 2 Positive Metastatic Gastroesophageal Junction or Gastric Cancer; ID NUMBER:11-1669: Afatinib and Paclitaxel in Patients With Advanced HER2-Positive Trastuzumab-Refractory Advanced Esophagogastric Cancer; NIEGA: Study of Nimotuzumab and Irinotecan as Second Line With Recurrent or Metastatic Gastric Adenocarcinoma; ENRICH: Study of Nimotuzumab and Irinotecan as Second Line With Advanced or Recurrect Gastric and Gastroesophageal Junction Cancer; CheckMate649: Efficacy Study of Nivolumab Plus Ipilimumab or Nivolumab Plus Chemotherapy Against Chemotherapy in Stomach Cancer or Stomach/Esophagus Junction Cancer; ATTRACTION-4: Study of ONO-4538 in Gastric Cancer; JAVELIN: Gastric 100Avelumab in First-Line Maintenance Gastric Cancer; KEYNOTE-062: Study of Pembrolizumab as First-Line Monotherapy and Combination Therapy for Treatment of Advanced Gastric or Gastroesophageal Junction Adenocarcinoma; SPOTLIGHT: A Phase 3 Efficacy, Safety and Tolerability Study of Zolbetuximab Plus mFOLFOX6 Chemotherapy Compared to Placebo Plus mFOLFOX6 as Treatment for Gastric and Gastroesophageal Junction Cancer; ILUSTRO: A Study to Assess the Antitumor Activity, Safety, Pharmacokinetics and Biomarkers of Zolbetuximab in Participants With Claudin 18.2 Positive, Metastatic or Advanced Unresectable Gastric and Gastroesophageal Junction Adenocarcinoma; GLOW: A Study of Zolbetuximab Plus CAPOX Compared With Placebo Plus CAPOX as First-line Treatment of Subjects With Claudin 18.2-Positive, HER2-Negative, Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma; ANGEL: Efficacy and Safety Trial of Apatinib Plus Best Supportive Care Compared to Placebo Plus Best Supportive Care in Patients With Gastric Cancer; INTEGRATEII: A Study of Regorafenib in Refractory Advanced Gastro-Oesophageal Cancer, Best supportive care; HER2: Human epidermal growth factor receptor 2; EGFR: Epidermal growth factor receptor; PD-L1: Programmed death ligand 1; PD-1: Programmed cell death protein 1; CTLA-4: Cytotoxic T-lymphocyte-associated antigen 4; CLDN18.2: Claudine-18.2; VEGFR1-3: Vascular endothelial growth factor receptor 1-3; FGFR: Fibroblastic growth factor receptor; PDGFR-β: Platelet-derived growth factor receptor beta; RAF: Serine/threonine-specific protein kinases RAF; RET: Rearranged during transfection; KIT: Tyrosine-protein kinase Kit.