Precision medicine in gastric cancer

Table 1 Clinical trials classified on molecular targets

Signaling	Molecular target	Therapeutic agents	Clinical trial (Identifier)	Type of trial	Line of treatment	Phase	Patient's stage	Status	Ref.
EGFR	HER2	Trastuzumab ± 5-FU/cisplatin/capecitabine	ToGA (NCT01041404)	Multicenter, randomized, open-label	First	III	Advanced gastric cancer, HER2-positive	Completed	[124]
	HER2	Trastuzumab/TS-1/cisplatin	NCT01736410	Multicenter, non-randomized, open-label	First	II	Advanced gastric cancer, HER2-positive	Completed	[125]
	HER2	Trastuzumab emtansine vs docetaxel-paclitaxel	GATSBY (NCT016441939)	Multicenter, randomized, open-label	Second	II/III	Advanced gastric cancer, HER2-positive	Completed	[126]
	HER2	Pertuzumab ± trastuzumab/5-FU/cisplatin/capecitabine	JACOB (NCT01774786)	Multicenter, randomized, double	First	III	Metastatic gastric cancer, HER2-positive	Active	[127]
	HER2	Lapatinib ± oxaliplatin/capecitabine	TRIO-013/LOGiC (NCT00680901)	Multicenter, randomized, quadruple	First	III	Advanced/metastatic gastric cancer, HER2-positive	Active	[128]
	HER2	IMU-131 vaccine (HER-Vaxx) + 5-FU/cisplatin or capecitabine	NCT02795988	Non-randomized, open-label	First/second	Ib/II	Advanced/metastatic gastric cancer, HER2-positive	Recruiting	[130]
	HER2	Pyrotinib	(NCT02500199)	Open-label	Second	I	Advanced gastric cancer, HER2-positive	Recruiting	[131]
	HER2	Pyrotinib ± docetaxel	(NCT02378389)	Open-label	Second	I	Advanced gastric cancer, HER2-positive	Recruiting	[132]
	EGFR	Cetuximab ± cisplatin/capecitabine	EXPAND (NCT00678535)	Multicenter, randomized, open-label	First	III	Advanced gastric cancer	Completed	[134]
	EGFR	Panitumumab + 5-FU/cisplatin/docetaxel	NCT01716546	Multicenter, open-label	First	I/II	Locally advanced/metastatic gastric cancer	Terminated	[135]
	EGFR	Nimotuzumab + irinotecan vs irinotecan	ENRICH (NCT01813253)	Randomized, open-label	Second	III	Advanced/recurrent gastric cancer, EFGR overexpressed	Terminated	[136]
	EGFR	Nimotuzumab ± S-1/cisplatin	NCT02370849	Randomized, open-label	First	II	Locally advanced/metastatic gastric cancer	Completed	[138]
mTOR/PI3K/AKT	mTOR	Everolimus	NCT00519324	Multicenter, open-label	Second/third	II	Advanced/metastatic, refractory gastric cancer	Completed	[142]
	mTOR	Everolimus	NCT00729482	Open-label	Second	II	Advanced, refractory gastric cancer	Completed	[143]
	mTOR	Everolimus + BSC vs placebo + BSC	GRANITE-1 (NCT00879333)	Multicenter, randomized, quadruple	Second/third	III	Advanced gastric cancer	Completed	[144]
	PI3KCA	Alpelisib + AUY922	NCT01613950	Multicenter, open-label	Second/third	Ib	Advanced/metastatic gastric cancer, PIK3CA mutations and/or HER2 amplification	Completed	[145]
	AKT	Ipatasertib ± 5FU/oxaliplatin/leucovorin	NCT01896531	Randomized, double	Second	II	Advanced/metastatic gastric cancer	Active	[146]
HGF/MET	HGF	Rilotumumab vs rilotumumab ± epirubicin/cisplatin/capecitabine	NCT00719550	Multicenter, randomized	First	Ib/II	Locally advanced/metastatic gastric cancer	Completed	[149]
	HGF	Rilotumumab ± epirubicin/cisplatin/capecitabine	RILOMET-1 (NCT01697072)	Multicenter, randomized, triple	First	III	Locally advanced/metastatic gastric cancer, MET-positive	Terminated	[150]
	HGF	Rilotumumab ± /cisplatin/capecitabine	RILOMET-2 (NCT02137343)	Multicenter, randomized, triple	First	III	Advanced gastric cancer	Terminated	[151]
	MET	Onartuzumab ± 5-FU/leucovorin/oxaliplatin	NCT01662869	Multicenter, randomized, double	First	III	Metastatic gastric cancer, HER2 negative, MET-positive	Completed	[152]
VEGF/VEGFR	VEGFR2	Ramucirumab + BSC vs placebo + BSC	REGARD (NCT00917384)	Randomized, quadruple	First	III	Metastatic/locally recurrent gastric cancer	Completed	[72]
	VEGFR2	Ramucirumab ± paclitaxel	RAINBOW (NCT01170663)	Multicenter, randomized, double	Second	III	Metastatic, refractory gastric cancer	Completed	[73]
	VEGFR2	Apatinib vs placebo	NCT01512745	Randomized, quadruple	Third	III	Advanced/metastatic refractory gastric cancer	Completed	[156]
TP53	TP53	Polymorphisms of xenobiotic metabolism, DNA repair, and TP53 genes	NCT01470404				Gastric cancer treated with adjuvant chemotherapy	Completed	[161]
	TP53	APR-246 + 5-FU/cisplatin	NCT02999893	Open-label	Second	I/II	Advanced/metastatic platinum resistant gastroesophageal cancer, TP53 mutated	Recruiting	[167]
	TP53	AZD1775 (WEE inhibitor) + paclitaxel	NCT02448329	Single center	Second	II	Advanced gastric cancer, TP53 mutated	Recruiting	[169]
	TP53	HDM201 (inhibitor TP53/MDM2 interaction)	NCT02143635	Multicenter, non-randomized, open-label	Second	I	Advanced/metastatic gastric cancer, TP53 wild-type	Active	[170]
PARP	PARP	Olaparib + paclitaxel vs paclitaxel	Study 39 (NCT01063517)	Multicenter, randomized, double	Second	II	Metastatic/recurrent gastric cancer, low ATM expression	Active	[174]
	PARP	Olaparib + paclitaxel vs placebo + paclitaxel	GOLD (NCT01924533)	Multicenter, randomized, double	Second	III	Advanced gastric cancer	Active	[175]
	PARP	Olaparib + ramucirumab	NCT03008278	Open-label	Second	I/II	Metastatic/recurrent gastric cancer	Recruiting	[178]
	PARP	Veliparib + FOLFIRI	NCT01123876	Open-label	First/second	I	Advanced gastric cancer	Completed	[179]
Immune Checkpoint	PD-1	Pembrolizumab vs pembrolizumab ± 5FU/cisplatin or capecitabine	KEYNOTE-059 (NCT02335411)	Multicenter, non-randomized, open-label	Second/third	II	Metastatic/recurrent gastric cancer	Active	[181]
	PD-1	Pembrolizumab vs paclitaxel	KEYNOTE-061 (NCT02370498)	Randomized, open-label	Second	III	Advanced gastric cancer	Active	[183]
	PD-1	Pembrolizumab vs pembrolizumab ± 5FU/cisplatin or capecitabine	KEYNOTE-062 (NCT02494583)	Randomized, quadruple	First	III	Advanced gastric cancer	Active	[184]
	PD-1	Pembrolizumab ± 5-FU/cisplatin or oxaliplatin/capecitabine	KEYNOTE-0859 (NCT03675737)	Randomized, double	First	III	Advanced/metastatic gastric cancer	Recruiting	[185]
	PD-1	Pembrolizumab/trastuzumab ± cisplatin/capecitabine/oxaliplatin	NCT02954536	Single group, open-label	First	II	Advanced/metastatic gastric cancer, HER2-positive	Recruiting	[186]
	PD-1	Nivolumab vs placebo	ATTRACTION-2 (NCT02267343)	Multicenter, randomized, quadruple	Second	III	Advanced/recurrent gastric cancer	Active	[187]
	PD-1	Nivolumab ± capecitabine/oxaliplatin	ATTRACTION-4 (NCT02746796)	Multicenter, randomized, quadruple	First	II/III	Advanced/recurrent refractory gastric cancer	Active	[188]
	PD-1	Nivolumab ± ipilimumab	CHECKMATE-032 (NCT01928394)	Multicenter, randomized, open label	First/second	I/II	Advanced/metastatic, refractory gastric cancer	Active	[189]
	PD-1	Nivolumab ± ipilimumab vs nivolumab + chemotherapy vs chemotherapy	CHECKMATE-649 (NCT02872116)	Multicenter, randomized, open-label	First	III	Advanced/metastatic gastric cancer	Recruiting	[190]
	PD-1	Tislelizumab ± oxaliplatin/capecitabine or 5-FU/cisplatin	NCT03777657	Randomized, triple	First	III	Locally advanced/metastatic gastric cancer	Recruiting	[191]

EGFR: Epidermal growth factor receptor; mTOR: Mechanistic target of rapamycin kinase; HGF: Hepatocyte growth factor; VEGF: Vascular endothelial growth factor; TP53: Tumor protein p53; PARP: Poly (ADP-ribose) polymerase; PD-1: Programmed cell death 1.