Table 3.
Collections of clinical trials related to targeted therapy and immunotherapy for gastric cancer
| Study | Phase | Design | Patients | Target | Drug | Treatment | Number of patients | Line of therapy | Results |
|---|---|---|---|---|---|---|---|---|---|
| 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 | 1st | 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 2nd | Improved OS |
| NCT03556345583,584 | II | Single arm, open label, single-center | Repeated-treated advanced HER2 positive GC | HER2 | Disitamab vedotin (RC48) | RC48-ADC | 125 | 2nd or after 2nd | 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 | 1st or after 1st | 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 | 1st | 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 | 1st | 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 | 1st | 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 | 1st | 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 | 2nd | 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 2nd | 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 | 1st | 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 | 2nd or after 2nd | 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 | 2nd | 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 | 1st | 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 | 1st | 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 | 2nd or after 2nd | 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 2nd | 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 | 1st | 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 | 1st | 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 | 1st | 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 | 2nd | 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 | 1st | 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 | 2nd or after 2nd | 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 | 1st, 2nd | Ongoing |
| NCT04117958 | I | Single arm, open label, multi-center | MUC17-positive solid tumors including G/GEJ | CD3 and MUC17 | AMG 199 | AMG 199 | 165 | 3rd | Ongoing |
| NCT01045538630 | I/II | Single arm, open label, single-center | Unresectable GC | HDAC | Vorinostat | Vorinostat+capecitabine+cisplatin | 45 | 1st | ORR is 42%, more adverse events |
| NCT01386346629 | I | Single arm, open label, single-center | Advanced or metastatic gastric cancer | DNMT | Azacitidine | Azacitidine+chemotherapy | 12 | 1st | ORR is 67%, well-tolerated |
HER2 human epidermal growth factor receptor 2, OS overall survival rate, EGFR epidermal growth factor receptor, PFS progression-free survival, ORR overall response rate, VEGF vascular endothelial growth factor, VEGFR2 vascular endothelial growth factor receptor 2, c-MET tyrosine-protein kinase mesenchymal-epithelial transition factor, FGFR2b fibroblast growth factor receptor 2b, PD-1 programmed death-ligand 1, CTLA-4 cytotoxic T-lymphocyte-associated protein 4, GEJ gastroesophageal junction, IHC intrahepatic cholestasis, ADC antibody-drug conjugate, CapeOx/XELOX oxaliplatin + capecitabine, EOX epirubicin + oxaliplatin + capecitabine, FOLFOX leucovorin + 5-FU + oxaliplatin, CAR chimeric antigen receptor, FAK focal adhesion kinase, DKK Dickkopf, CD3 cluster of differentiation 3, HDAC histone deacetylases, DNMT DNA methyltransferase.