Molecular-targeted therapy toward precision medicine for gastrointestinal cancer: Current progress and challenges

Table 2 Clinic al trials for gastric cancer classified on molecular targets

Clinical Trials gov idntifier	Agents	Type of trial	Line of treatment	Phase	Results	Comments
EGFR
NCT01813253	Nimotuzumab	Randomized, open label	Second	III	Terminated	Nimotuzumab + irinotecan
NCT02370849	Nimotuzumab	Randomized, open label	First	II	Completed	Nimotuzumab + cisplatin + S-1
NCT03130790	Varlitinib	Randomized, double	First	II/III	Active, not recruiting	Varlitinib; mFOLFOX6
NCT01743365	Afatinib	Nonr-andomized, open-label	First	II	Completed	Afatinib ± 5-FU/cisplatin
NCT02501603	Afatinib	Single group, open label	Second	II	Recruiting	Afatinib + paclitaxel
NCT01746771	Poziotinib (target EGFR/HER2/HER4)	Single group, open label	First	I/II	Completed	Poziotinib + Paclitaxel + Trastuzumab in HER2-positive GC
HER2(3)
NCT01152853	Vizimpro	Single group, open label	Second	II	Completed	Vizimpro
NCT01602406	LJM716	Single group, open label	Second	I	Completed	LJM716 + Trastuzumab
NCT03329690(DESTINY-Gastric01)	DS-8201a	Randomized, open label	Third	II	Active, not recuruiting	DS-8201a + physician’s choice treatment
NCT03619681	KN026	Single group, open label	N.A.	I	Recruiting	KN026 in HER2-positive GC
NCT02689284	Margetuximab	Single group, open-label	Third	I/II	Active, not-recruiting	Margetuximab + pembrolizumab
FGFR
NCT04071184	Alofanib	Single group, open label	Third	I	Recruiting	Alofanib
NCT02699606	Erdafitinib	Single group, open label	Second	II	Recruiting	Erdafitinib
NCT03694522	Bemarituzumab (FPA144)	Randomized, double blinded	First	II	Active, not recuiting	Bemarituzumab + mFOLFOX6
NCT04149691	CPL304110	Single group, open label	Third	I	Recruiting	CPL304110
VEGFR
NCT03817411	Telatinib (target VEGFR/PDGFα/c-Kit)	Randomized, quadruple	First	II	Recruting	Telatinib + capecitabine/oxaliplatin
NCT01238055	Sunitinib (target VEGFR/PDGFR)	Randomized, open label	Second	II	Completed	Sunitinib + docetaxel
NCT01719549	Dovitinib (target FLT3/c-Kit/ FGFR1/3/VEGFR1/2/3/PDGFR/CFS-1R)	Single group, open label	Third	II	Completed	Dovitinib as a salvage chemotherapy
NCT01921673	Dovitinib	Single group, open label	Second	I/II	Completed	Dovitinib + docetaxel
NCT04286711	Apatinib (target VEGFR2/c-Kit/Src)	Single group, open label	Second	I/II	Not yet recruiting	Apatinib + Camrelizumab + Albumin-paclitaxel
NCT03286244	Vorolanib (target VEGFR/PDGFR/CSF1R)	Single group, open label	Second	I	Recruiting	Vorolanib + paclitaxel
NCT01716546	Pazopanib (target VEGFR/PDGFR/FGFR/c-Kit)	Single group, open label	First	I/II	Terminated	Pazopanib + DCF
NCT03609359	Lenvatinib (target VEGFR2/3)	Single group, open label	N.A.	II	Active, not recruiting	Lenvatinib + pembrolizumab
NCT03941873	Sitravatinib (target VEGFR1/2/3, Axl, MER, KIT, FLT3, DDR2, RET)	Nonr-andomized, open-label	Third	I/II	Recruiting	Sitravatinib + Tislelizumab
AKT
NCT02451956	AZD5363	Single group, open label	Second	II	Completed	AZD5363 + paclitaxel in PIK3CA mutation or/and amplification GC
NCT02240212	Afuresertib	Non-Randomized, open-label	Second	I	Completed	Afuresertib + paclitaxel
PI3KCA
NCT01613950	Alpelisib	Single group, open label	Second/third	I	Completed	Alpelisib + AUY922 in GC mutated PI3KCA
MET
NCT02096666	AMG337	Single group, open label	Third	I/II	Completed	AMG337
NCT03542877	Cabozantinib (target MET/RET/VEGFR-2)	Single group, open label	Third	I	Recruiting	Cabozantinib + durvalumab
TGF-β
NCT03724851	Vactosertib (target TGFBR1/ALK4/5)	Single group, open label	Second	I/II	Recuriuting	Vactosertib + pembrolizumab
PARP
NCT01063517(Study 39)	Olaparib	Multicenter, randomized, double	Second	II	Active, not recruiting	Olaparib + paclitaxel vs paclitaxel
NCT01924533(GOLD)	Olaparib	Multicenter, randomized, double	Second	III	Active, not recruiting	Olaparib + paclitaxel vs placebo + paclitaxel
NCT03008278	Olaparib	Randomized, open-label	First	I/II	Recruiting	Olaparib + ramucirumab
NCT03427814	Pamiparib	Randomized, double	Second	II	Active, not recruiting	Pamiparib
NCT04178460	Niraparib	Single group, open label	Second	I	Recruiting	Niraparib + MGDO013
NCT03995017	Rucaparib	Non-randomized, open-label	Third	I/II	Recruiting	Rucaparib + ramucirumab + nivolumab
STAT
NCT02178956	Napabucasin	Randomized, quadruple	Second	III	Completed	Napabucasin + paclitaxel
ALK
NCT02435108	Crizotinib (target ALK/ROS1/MET)	Single group, open label	Third	II	Completed	Crizotinib for c-MET positive GC
NCT03698825	Vactosertib (target ALK4/5)	Single group, open label	Thurd	I/II	Recruiting	Vactosertib+paclitaxel
CDK
NCT03480256	SHR6390 (target CDK 4/6)	Sequential Assigment, open label	Second	I	Recruiting	SHR6390 + pyrotinib in HRE2 positive GC
NCT03311334	Alvocidib (target CDK9)	Non-randomized, open-label	Third	I/II	Recruiting	Alvocidib+nivolumab or pembrolizumab
HSP90
NCT01402401	Luminespib	Single group, open label	Second	II	Terminated	Luminespib + trastuzumab
Hedgehog
NCT03052478	Vismodegib	Single group, open label	Second	II	Active, not recruiting	Vismodegib
NCT04007744	Sonidegib	Single group, open label	Second	I	Recruiting	Sonidegib + pembrolizumab
DKK1
NCT04363801(DisTinGuish)	DKN-01	Non-randomized, open label	First or Second	II	Not yet recruiting	DKN-01 + ttsleizumab + chemotherapy
CLDN18.2
NCT03528629	Zolbetuximab	Non-randomized, open label	Third	I	Completed	Zolbetuximab
NCT03504397	Zolbetuximab	Randomized, double	First	III	Recruiting	Zolbetuxima + mFOLFOX6
NCT03653507	Zolbetuximab	Randomized, double	First	III	Recruiting	Zolbetuximab + CAPOX in CLDN-positive, HER2-negative GC
NCT01671774	IMAB362	Non-randomized, open label	First	I	Completed	IMAB362 + zoledronicacid + interleukin-2

GC: Gastric cancer; PI3K: Phosphoinositide 3-kinase; AKT: Protein kinase B; also known as PKB; mTOR: Mammalian target of rapamycin; MEK: Mitogen-activated protein kinase, EGFR: Epidermal growth factor receptor; HER2/3/4: Human epidermal growth factor 2/3/4; MAPK: Mitogenactivated protein kinase; STAT3: Signal transducer and activator of transcription 3; VEGF: Vascular endothelial growth factor; VEGFR: Vascular endothelial growth factor receptor; EGFR Epidermal growth factor receptor; PDGFR: Platelet-derived growth factor receptor; FGFR: Fibroblast growth factor receptor; HGF: Hepatocyte growth factor; MET: Mesenchymal-epithelial transition factor; TEK: Tunica interna endothelial cell kinase; DDR: Discoidin domain receptor tyrosine kinase; MKNK/MAP: Kinase-interacting serine/threonine protein kinase; FLT3: Fms-related tyrosine kinase 3, MEK: Mitogen-activated protein kinase; N.A.: Not applicable; MSS: Microsatellite stable; HDAC: Histone deacetylases; CLDN: Claudin.