TABLE 2.
Complete and ongoing clinical trials of therapeutic agents targeting gastric and/or colorectal CSCs, correlated signaling pathways and the transcription factor STAT3.
| Drug/Antibody | Targets | Disease/Condition | NCT Identifier | Phase | Routes of administration | Recruitment status | Last update | Sponsor |
|
Immunotherapy | ||||||||
| RO5429083 | CD44 | Metastatic and/or locally advanced malignant solid tumors | NCT01358903 | I | Intravenous (IV) | Completed, no results posted | November 2016 | Hoffmann-La Roche |
| Adecatumumab alone or in combination with FOLFOX | EpCAM | R0 resection of colorectal liver metastases | NCT00866944 | II | Intravenous (IV) | Completed, no results posted | November 2011 | Amgen Research (Munich) GmbH |
| MCLA-158 | EGFR and Lgr5 | Advanced/metastatic solid tumors, including CRC | NCT03526835 | I | Intravenous (IV) | Recruiting | August 2018 | Merus N.V. |
| EpCAM CAR-T | EpCAM | Relapsed or refractory EpCAM positive cancer | NCT03013712 | I/II | Intravenous (IV) | Recruiting | January 2017 | First Affiliated Hospital of Chengdu Medical College |
| EpCAM CAR-T | EpCAM | Advanced GC with peritoneal metastasis | NCT03563326 | I | Intravenous (IV) | Recruiting | September 2018 | Jian-Kun Hu |
| EpCAM CAR-T | EpCAM | GC | NCT02725125 | — | Intravenous (IV) | Unknown | March 2017 | Sinobioway Cell Therapy Co., Ltd. |
| CART-133 | CD133 | Chemotherapy refractory advanced malignancies, including CRC | NCT02541370 | I/II | Intravenous (IV) | Completed, no results posted | December 2019 | Chinese PLA General Hospital |
|
Transcription Factor inhibitors | ||||||||
| BBI608 or BNC105 in combination with nivolumab | STAT3 | Metastatic CRC | NCT03647839 | II | Oral and Intravenous (IV) | Recruiting | February 2019 | Australasian Gastro-Intestinal Trials Group |
| Danvatirsen (AZD9150) in combination with Durvalumab (MEDI4736) | STAT3 | Advanced and refractory pancreatic, non-small cell lung cancer, and mismatch repair deficient CRC | NCT02983578 | II | Intravenous (IV) | Recruiting | March 2020 | M.D. Anderson Cancer Center |
| Napabucasin (GB201) in combination with FOLFIRI | STAT3 | Metastatic CRC | NCT03522649 | III | Oral and Intravenous (IV) | Recruiting | June 2019 | 1Globe Health Institute LLC |
| TTI-101 | STAT3 | Advanced cancers, including gastric adenocarcinoma and CRC | NCT03195699 | I | Oral | Recruiting | February 2020 | Tvardi Therapeutics, Incorporated |
| Artesunate, prior to surgery | β-catenin | Stage II/III CRC | NCT02633098 | II | Oral | Recruiting | April 2019 | St George’s, University of London |
| DKN-01 in combination with atezolizumab | DKK1 | GC | NCT04166721 | I/II | Intravenous (IV) | Recruiting | February 2020 | Royal Marsden NHS Foundation Trust |
| ETC-1922159 in combination with pembrolizumab | PORCN | Advanced solid tumors | NCT02521844 | I | Oral and Intravenous (IV) | Active, not recruiting | October 2019 | EDDC (Experimental Drug Development Centre), A*STAR Research Entities |
| Foxy-5 | Wnt-5A | CRC | NCT02020291 | I | Intravenous (IV) | Completed, no results posted | February 2016 | WntResearch AB |
| Foxy-5 | Wnt-5A | Metastatic breast, colon or prostate cancer | NCT02655952 | I | Intravenous (IV) | Completed, no results posted | December 2018 | WntResearch AB |
| Foxy-5 as neo-adjuvant therapy | Wnt-5A | Colon cancer | NCT03883802 | II | Intravenous (IV) | Recruiting | April 2019 | WntResearch AB |
| Genistein in combination with FOLFOX or FOLFOX-Avastin | tyrosine kinase and topoisomerase-II | Metastatic CRC | NCT01985763 | I/II | Oral and Intravenous (IV) | Completed, has results | May 2019 | Sofya Pintova |
| LGK974 | PORCN | Malignancies dependent on Wnt ligands, including BRAF mutant CRC | NCT01351103 | I | Oral | Recruiting | February 2020 | Novartis Pharmaceuticals |
| LGK974 in combination with LGX818 and cetuximab | PORCN | BRAF-mutant metastatic CRC and Wnt pathway mutations metastatic CRC | NCT02278133 | I/II | Oral | Completed, no results posted | October 2017 | Array BioPharma |
| MCLA-158 | EGFR and LGR5 | Advanced/metastatic solid tumors, including CRC | NCT03526835 | I | Intravenous (IV) | Recruiting | August 2018 | Merus N.V. |
| Mesalazine | induces the expression of μ-protocadherin | CRC | NCT02077777 | II | Oral | Completed, no results posted | December 2016 | SOFAR S.p.A. |
| OMP-18R5 (Vantictumab) | Wnt receptor | Solid tumors | NCT01608867 | I | Intravenous (IV) | Completed, no results posted | September 2016 | OncoMed Pharmaceuticals, Inc. |
| OMP-54F28 (Ipafricept) | Wnt receptor | Solid tumors | NCT01608867 | I | Intravenous (IV) | Completed, no results posted | July 2017 | OncoMed Pharmaceuticals, Inc. |
|
Hedgehog (Hh) pathway inhibitors | ||||||||
| BMS-833923 (XL139) | Smoothened | Advanced or metastatic solid tumors | NCT01413906 | I | Oral | Completed, no results posted | June 2013 | Bristol-Myers Squibb |
| BMS-833923 in combination with cisplatin and capecitabine | Smoothened | Metastatic gastric, gastroesophageal, or esophageal adenocarcinomas | NCT00909402 | I | Oral and Intravenous (IV) | Completed, no results posted | June 2013 | Bristol-Myers Squibb |
| LDE255 (Sonidegib) in combination with BKM120 (Buparlisib) | Smoothened (and PI3K) | Advanced solid tumors | NCT01576666 | I | Oral | Completed, no results posted | February 2016 | Novartis Pharmaceuticals |
| LEQ-506 | Smoothened | Advanced solid tumors | NCT01106508 | I | Oral | Completed, no results posted | February 2020 | Novartis Pharmaceuticals |
| Vismodegib in combination with standard chemotherapy | Smoothened | Advanced GC or gastroesophageal junction cancer | NCT00982592 | II | Oral and Intravenous (IV) | Completed, has results | January 2016 | National Cancer Institute (NCI) |
| Vismodegib (GDC-0449) with concurrent chemotherapy and bevacizumab as first-line therapy | Smoothened | Metastatic CRC | NCT00636610 | II | Oral | Completed, has results | June 2017 | Genentech, Inc. |
|
NOTCH pathway inhibitors | ||||||||
| BMS-906024 | Pan-Notch | Advanced or metastatic solid tumors | NCT01292655 | I | Intravenous (IV) | Completed, no results posted | January 2020 | Bristol-Myers Squibb |
| CB-103 | Pan-Notch | Advanced or metastatic solid tumors, including CRC | NCT03422679 | I/II | Oral | Recruiting | May 2019 | Cellestia Biotech AG |
| LY3039478 (Crenigacestat) | Pan-Notch | Advanced solid tumors | NCT02836600 | I | Oral | Active, not recruiting | December 2019 | Eli Lilly and Company |
| LY3039478 (Crenigacestat) in combination with other anticancer agents | Pan-Notch | Advanced or metastatic solid tumors | NCT02784795 | I | Oral and Intravenous (IV) | Completed, no results posted | March 2020 | Eli Lilly and Company |
| LY900009 | γ-Secretase | Advanced cancer | NCT01158404 | I | Oral | Completed, has results | August 2019 | Eli Lilly and Company |
| MEDI0639 | DLL4 | Advanced solid tumors | NCT01577745 | I | Intravenous (IV) | Completed, has results | May 2017 | MedImmune LLC |
| REGN421 (SAR153192; Enoticumab) | DLL4 | Advanced solid malignancies | NCT00871559 | I | Intravenous (IV) | Completed, no results posted | March 2014 | Regeneron Pharmaceuticals |
| RO4929097 | γ-Secretase | Recurrent and metastatic CRC | NCT01116687 | II | Oral | Completed, has results | May 2014 | National Cancer Institute (NCI) |
| RO4929097 in combination with capecitabine | γ-Secretase | Refractory solid tumors | NCT01158274 | I | Oral | Completed, no results posted | November 2014 | National Cancer Institute (NCI) |
| RO4929097 in combination with cediranib maleate | γ-Secretase | Advanced solid tumors including CRC | NCT01131234 | I | Oral | Completed, no results posted | December 2014 | National Cancer Institute (NCI) |
|
PI3K/AKT/mTOR pathway inhibitors | ||||||||
| Acetylsalicylic acid (aspirin) | — | CRC stage I-III with mutations in the PI3K signaling pathway | NCT02647099 | III | Oral | Recruiting | August 2019 | Anna Martling |
| Acetylsalicylic acid (aspirin) | — | Resected colon cancer with PI3K mutation stage II or III high risk | NCT02945033 | III | Oral | Recruiting | October 2019 | University Hospital, Rouen |
| Acetylsalicylic acid (aspirin) | — | Dukes C and high-risk dukes B CRCs | NCT00565708 | III | Oral | Recruiting | September 2019 | National Cancer Centre, Singapore |
| Acetylsalicylic acid (aspirin) and metformin | — | Stage I–III CRC patients | NCT03047837 | II | Oral | Recruiting | February 2019 | Ente Ospedaliero Ospedali Galliera |
| AZD2014 (Vistusertib) | mTORC1 and mTORC2 | RICTOR amplified GC | NCT03061708 | II | Oral | Terminated (lack of efficacy) | May 2019 | Samsung Medical Center |
| AZD2014 (Vistusertib) | mTORC1 and mTORC2 | TSC1/2 mutated or TSC1/2 null GC | NCT03082833 | II | Oral | Terminated (lack of efficacy) | May 2019 | Samsung Medical Center |
| AZD5363 in combination with paclitaxel | AKT | Advanced gastric adenocarcinoma | NCT02451956 | II | Oral and Intravenous (IV) | Completed, no results posted | December 2019 | Samsung Medical Center |
| AZD8186 in combination with paclitaxel | PI3K β/δ | Advanced GC | NCT04001569 | I/II | Oral and Intravenous (IV) | Recruiting | June 2019 | Seoul National University Bundang Hospital |
| BKM120 (Buparlisib) in combination with LDE255 (Sonidegib) | PI3K and Smoothened | Advanced solid tumors | NCT01576666 | I | Oral | Completed, no results posted | February 2016 | Novartis Pharmaceuticals |
| BYL719 (Alpelisib) in combination with AUY922 | PI3K | Advanced or metastatic GC | NCT01613950 | I | Oral and Intravenous (IV) | Completed, no results posted | February 2020 | Novartis Pharmaceuticals |
| BYL719 (Alpelisib) in combination with LGX818 (Encorafenib) and Cetuximab | BRAF, EGFR and PI3K | in BRAF Mutant Metastatic CRC | NCT01719380 | I/II | Oral and Intravenous (IV) | Completed, no results posted | April 2019 | Array BioPharma |
| Cabozantinib | Multikinases | Refractory metastatic CRC | NCT03542877 | II | Oral | Active, not recruiting | April 2019 | Academic Thoracic Oncology Medical Investigators Consortium |
| CB-839 (Telaglenastat) in combination with capecitabine | Glutaminase | Solid tumors and fluoropyrimidine resistant PIK3CA mutant CRC | NCT02861300 | I/II | Oral | Recruiting | March 2020 | Case Comprehensive Cancer Center |
| Copanlisib in combination with anti-PD-1 antibody Nivolumab | PI3K | Relapsed/refractory solid tumors, mismatch-repair proficient (MSS) CRC | NCT03711058 | I/II | Intravenous (IV) | Recruiting | July 2019 | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins |
| DS-7423 | PI3K and mTOR | Advanced solid malignant tumors | NCT01364844 | I | Oral | Completed, no results posted | February 2014 | Daiichi Sankyo, Inc. |
| Ipatasertib (GDC-0068) in combination with oxaliplatin, 5-FU and leucovorin | AKT | Advanced or metastatic GC or gastroesophageal junction cancer | NCT01896531 | II | Oral and Intravenous (IV) | Active, not recruiting | February 2020 | Genentech, Inc. |
| MK-2206 | AKT | Advanced GC or gastroesophageal junction cancer | NCT01260701 | II | Oral | Completed, has results | January 2016 | National Cancer Institute (NCI) |
| MK-2206 | AKT | CRC that is metastatic or locally advanced and cannot be removed by surgery | NCT01802320 | II | Oral | Completed, has results | September 2019 | National Cancer Institute (NCI) |
| MK-2206 in combination with AZD6244 (Selumetinib) | AKT and MEK | Advanced CRC | NCT01333475 | II | Oral | Completed, has results | September 2015 | National Cancer Institute (NCI) |
| Neratinib in combination with Trastuzumab or with Cetuximab | HER2 and EGFR | KRAS/NRAS/BRAF/PIK3CA wild-type metastatic CRC by HER2 status | NCT03457896 | II | Oral | Recruiting | November 2019 | NSABP Foundation Inc |
| Pembrolizumab (MK-3475) combined with INCB050465 or with Itacitinib (INCB039110) | JAK1 and PI3K-delta | Advanced solid tumors, including CRC | NCT02646748 | I | Oral | Active, not recruiting | December 2019 | Incyte Corporation |
| PX-866 (Sonolisib) in combination with Cetuximab | PIP3 | Incurable metastatic CRC | NCT01252628 | I/II | Oral | Completed | May 2018 | Cascadian Therapeutics Inc. |
| RAD001 (Everolimus) | TOR serine-threonine kinases | Previously treated unresectable or metastatic esophageal cancer or GC | NCT00985192 | II | Oral | Completed, has results | February 2020 | Translational Oncology Research International |
| RAD001 (Everolimus) | TOR serine-threonine kinases | Advanced GC | NCT00519324 | II | Oral | Completed, no results posted | November 2015 | Novartis Pharmaceuticals |
| RAD001 (Everolimus) in combination with AV-951(Tivozanib) | TOR serine-threonine kinases and VEGFRs 1, 2, and 3 | Gastrointestinal cancer | NCT01058655 | I/II | Oral | Completed, has results | April 2017 | Dana-Farber Cancer Institute |
| RAD001 (Everolimus) in combination with Capecitabine and Oxaliplatin | TOR serine-threonine kinases | Advanced GC | NCT01049620 | I | Oral and Intravenous (IV) | Completed, no results posted | January 2020 | Asan Medical Center |
| RAD001 (Everolimus) in combination with cisplatin and HDFL (high-dose 5-FU and leucovorin) | TOR serine-threonine kinases | Advanced GC | NCT00632268 | II | Oral and Intravenous (IV) | Completed, no results posted | August 2013 | National Taiwan University Hospital |
| SAR245409 (Voxtalisib) in combination with MSC1936369B (pimasertib) | PI3K, MTOR, MEK1 and 2 | Advanced or metastatic solid tumors (GC not included) | NCT01390818 | I | Oral | Completed, has results | March 2017 | EMD Serono |
| Serabelisib in combination with Canagliflozin | PI3Kα and SGLT2 | Advanced solid tumors | NCT04073680 | I/II | Oral | Not yet recruiting | February 2020 | Petra Pharma |
| SF1126 | PI3K | Solid tumors | NCT00907205 | I | Intravenous (IV) | Completed, no results posted | June 2013 | Semafore Pharmaceuticals |
| Trametinib in combination with Trifluridine and Tipiracil Hydrochloride | MEK | Chemotherapy-resistant RAS-mutated (PIK3CA/PTEN-Wild-Type) metastatic CRC | NCT03317119 | I | Oral | Recruiting | January 2020 | City of Hope Medical Center |
GC corresponds to gastric cancer and CRC to colorectal cancer. FOLFOX corresponds to a chemotherapy regimen with folinic acid (leucovorin), fluorouracil (5-FU) and oxaliplatin (Eloxatin) and FOLFIRI corresponds to a chemotherapy regimen with folinic acid (leucovorin), fluorouracil (5-FU) and irinotecan (Camptosar).