Table 3 Collections of clinical trials related to targeted therapy and immunotherapy for gastric cancer

NCT01041404⁴⁰

III

Randomized, open label, multi-center

Locally advanced, metastatic HER2 positive G/GEJ cancer

HER2

Trastuzumab

Arm1: Trastuzumab+chemotherapy; Arm2: chemotherapy

Arm1/Arm2: 294/290

1^st

Improved OS

NCT03329690⁵⁸²

II

Randomized, open label, multi-center

Repeated-treated advanced HER2 positive G/GEJ cancer

HER2

Trastuzumab deruxtecan (DS-8201)

Arm1: DS-8201a; Arm2: irinotecan or paclitaxel

Arm1/Arm2: 125/62

After 2^nd

Improved OS

NCT03556345^583,584

II

Single arm, open label, single-center

Repeated-treated advanced HER2 positive GC

HER2

Disitamab vedotin (RC48)

RC48-ADC

125

2^nd or after 2^nd

ORR is 24.8%, manageable safety

NCT02892123⁵⁸⁵

I

Non-randomized, open label, multi-center

Repeated-treated, locally advanced or metastatic HER2 positive cancers

HER2

Zanidatamab (ZW25)

Arm1: ZW25; Arm2: ZW25 + chemotherapy

Arm1/Arm2: 36/26

1^st or after 1^st

ORR is 38% in Arm1 and 60% in Arm2

NCT00680901⁵⁸⁷

III

Randomized, quadruple blinded, multi-center

Locally advanced or metastatic HER2 positive G/GEJ cancer

HER2

Lapatinib

Arm1: CapeOx+lapatinib; Arm2: CapeOx+placebo

Arm1/Arm2: 249/238

1^st

Failed to improve OS

NCT00678535⁵⁸⁹

III

Randomized, open label, multi-center

Locally advanced G/GEJ cancer

EGFR

Cetuximab

Arm1: cetuximab+capecitabine+cisplatin; Arm2: capecitabine+cisplatin

Arm1/Arm2: 455/449

1^st

Failed to improve PFS

NCT00824785⁵⁹⁰

III

Randomized, open label, multi-center

Locally advanced or metastatic G/E/GEJ cancer

EGFR

Panitumumab

Arm1: EOX; Arm2: EOX + panitumumab

Arm1/Arm2: 275/278

1^st

Failed to improve OS

NCT00548548⁵⁹³

III

Randomized, double blinded, multi-center

Locally advanced or metastatic GC

VEGF

Bevacizumab

Arm1: bevacizumab; Arm2: placebo

Arm1/Arm2: 387/387

1^st

Failed to improve OS

NCT00917384⁵⁷⁷

III

Randomized, quadruple blinded, multi-center

Metastatic G/GEJ cancer

VEGFR2

Ramucirumab

Arm1: ramucirumab; Arm2: placebo

Arm1/Arm2: 238/117

2^nd

Improved OS

NCT01512745⁵⁹⁵

III

Randomized, quadruple blinded, multi-center

Repeated-treated advanced or metastatic GC

VEGFR2

Apatinib

Arm1:apatinib; Arm2: placebo

Arm1/Arm2: 176/91

After 2^nd

Improved OS

NCT01697072⁵⁹⁹

III

Randomized, triple blinded, multi-center

Untreated advanced MET positive G/GEJ cancer

c-MET

Rilotumumab

Arm1: rilotumumab; Arm2: placebo

Arm1/Arm2: 304/305

1^st

Failed to improve OS

NCT02299648⁶⁰¹

II

Single arm, open label, single-center

Metastatic or recurrent G/E/GEJ cancer

c-MET

Savolitinib

Savolitinib+docetaxel

25

2^nd or after 2^nd

ORR is 28%

NCT01457846⁶⁰²

II

Randomized, open label, multi-center

Advanced G/GEJ cancer with FGFR2 polysomy or gene amplification

FGFR2b

AZD4547

Arm1: AZD4547; Arm2: paclitaxel

Arm1/Arm2: 40/27

2^nd

Failed to improve PFS

NCT03343301,NCT03694522⁶⁰³

II

Randomized, double blinded, multi-center

Advanced G/GEJ cancer with FGFR2 overexpression or amplification

FGFR2b

Bemarituzumab (FPA144)

Arm1: bemarituzumab+mFOLFOX6; Arm2: placebo+mFOLFOX6

Arm1/Arm2: 77/78

1^st

Improved PFS

NCT01630083⁶⁰⁴

II

Randomized, open label, multi-center

Advanced Claudin18.2 positive G/E/GEJ cancer

Claudin18.2

Zolbetuximab

Arm1: EOX; Arm2: EOX + zolbetuximab 800/600 mg/m^2 Arm3: EOX + zolbetuximab 1000 mg/m^2;

Arm1/Arm2/Arm3: 84/77/85

1^st

Improved OS and PFS (Arm2 vs Arm1)

NCT03874897⁶⁰⁵

I

Single arm, open label, multi-center

Advanced Claudin18.2 positive G/GEJ and pancreatic cancer

Claudin18.2

CT041

CT041

37

2^nd or after 2^nd

ORR is 48.6%, acceptable safety profile

NCT02267343⁶⁰⁹

III

Randomized, quadruple blinded, multi-center

Unresectable or recurrent G/GEJ cancer refractory to or intolerant of standard therapy

PD-1

Nivolumab

Arm1: nivolumab; Arm2: placebo

Arm1/Arm2: 330/163

After 2^nd

Improved OS

NCT02872116⁶¹¹

III

Randomized, open label, multi-center

Untreated advanced HER2 negative G/E/GEJ cancer

PD-1

Nivolumab

Arm1: nivolumab+chemotherapy; Arm2: chemotherapy

Arm1/Arm2: 789/792

1^st

Improved OS

NCT02494583⁶¹⁰

III

Randomized, quadruple blinded, multi-center

Advanced G/GEJ cancer with PD-L1 CPS ≥ 1

PD-1

Pembrolizumab

Arm1: pembrolizumab; Arm2: pembrolizumab+chemotherapy; Arm3: placebo+chemotherapy;

Arm1/Arm2/Arm3: 256/257/250

1^st

OS of pembrolizumab is non-inferior to chemotherapy

NCT03615326⁶¹²

III

Randomized, quadruple blinded, multi-center

Untreated unresectable HER2 positive G/GEJ cancer

PD-1 and HER2

Pembrolizumab + trastuzumab

Arm1: pembrolizumab+trastuzumab+chemotherapy; Arm2: placebo+trastuzumab+chemotherapy

Arm1/Arm2: 217/217

1^st

Improved ORR: Arm1: 74.4%, Arm2: 51.9%

NCT01585987⁶¹⁴

II

Randomized, open label, multi-center

Unresectable or metastatic G/GEJ cancer

CTLA-4

Ipilimumab

Arm1: Ipilimumab; Arm2: best supportive care

Arm1/Arm2: 57/57

2^nd

Failed to improve PFS

NCT03852251

Ib/II

Single arm, open label, single-center

Uptreated unresectable G/GEJ cancer

PD-1 and CTLA-4

Cadonilimab (AK104)

AK104 with or without chemotherapy

34

1^st

ORR is 66.7% with acceptable safety profile

NCT05327231

Ib

Non-randomized, open label, multi-center

Previously treated locally advanced or metastatic G/GEJ cancer

FAK

IN10018

IN1001 with or without chemotherapy

33

2^nd or after 2^nd

Ongoing

NCT04363801

IIa

Non-randomized, open label, multi-center

Advanced or metastatic G/GEJ cancer

DKK1

DKN-01

DKN-01+tislelizumab with or without chemotherapy

72

1^st, 2^nd

Ongoing

NCT04117958

I

Single arm, open label, multi-center

MUC17-positive solid tumors including G/GEJ

CD3 and MUC17

AMG 199

AMG 199

165

3^rd

Ongoing

NCT01045538⁶³⁰

I/II

Single arm, open label, single-center

Unresectable GC

HDAC

Vorinostat

Vorinostat+capecitabine+cisplatin

45

1^st

ORR is 42%, more adverse events

NCT01386346⁶²⁹

I

Single arm, open label, single-center

Advanced or metastatic gastric cancer

DNMT

Azacitidine

Azacitidine+chemotherapy

12

1^st

ORR is 67%, well-tolerated