Table 3.
Overview of clinical trials (current and past clinical trials) evaluating activity of drugs targeting WNT pathway in melanoma, colorectal cancer and hepatocellular carcinoma (https://clinicaltrials.gov).
| Compound | Company | Target/Mode of Action | Type of Cancer | Trial Identifier (phase/status) | Ref. |
|---|---|---|---|---|---|
| WNT974 (with LGX818 & cetuximab) |
Array BioPharma | porcupine inhibitor | metastatic colorectal cancer |
NCT02278133 (Phase 1; Phase 2/completed; updated: October 2017) |
[184,185] |
| LGK974 (monotherapy or combined with PDR001) |
Novartis Pharmaceuticals | porcupine inhibitor | BRAF mutant colorectal cancer & melanoma |
NCT01351103 (Phase 1 /recruiting; updated: June 2020) |
[184,185] |
| ETC-1922159 (with pembrolizumab) |
EDDC, A*STAR Research Entities | porcupine inhibitor | colorectal cancer |
NCT02521844 (Phase 1/active, not recruiting; updated: October 2019) |
[186] |
| CGX1321 | Curegenix, Inc. | porcupine inhibitor | colorectal adenocarcinoma hepatocellular carcinoma |
NCT03507998 (Phase 1/ recruiting; updated: May 2019) |
[187] |
| CGX1321 (with pembrolizumab) |
Curegenix, Inc. | porcupine inhibitor | colorectal cancer |
NCT02675946 (Phase1/ recruiting updated: September 2019) |
[187] |
| PRI-724 | Prism Pharma Co., Ltd. | interaction of β-catenin and CBP |
colorectal cancer |
NCT01302405 (Phase 1 terminated due to low enrollment, updated: August 2017) |
[188] |
| DKN-01 (monotherapy or combined with sorafenib) |
Johannes Gutenberg University Mainz | DKK1 inhibitor | hepatocellular carcinoma |
NCT03645980 (Phase 1; Phase 2/recruiting; updated: August 2019) |
none |
| OMP-54F28 (ipafricept) with sorafenib |
OncoMed Pharmaceuticals, Inc. | FZD8 decoy receptor for WNT ligands | locally advanced or metastatic hepatocellular cancer solid tumors |
NCT02069145 (Phase 1/completed; updated: August 2017) |
[189] |
| OMP-54F28 (ipafricept) |
NCT01608867 (Phase 1/completed; updated: July 2017) |
||||
| OMP-18R5 (vantictumab) |
OncoMed Pharmaceuticals | FZD receptors (1, 2, 5, 7, 8) inhibitors |
solid tumors |
NCT01345201 (Phase 1/completed; updated: September 2016) |
[190] |
| Foxy-5 | WntResearch AB | WNT5A mimetic | colorectal cancer |
NCT02655952 & NCT02020291 (Phase 1/completed; updated: December 2018) NCT03883802 (Phase 2/recruiting; updated: April 2019) |
[191,192] |
| Metastatic colorectal cancer | |||||
| OMP-131R10 (with FOLFIRI) |
OncoMed Pharmaceuticals, Inc. | anti-R-spondin3 antibody | colorectal cancer |
NCT02482441 (Phase 1/completed; updated: August 2018) |
[193] |
| niclosamide | Michael Morse, MD | FZD1 internalization and BCL-9 inhibition, c-JUN upregulation |
colorectal cancer |
NCT02687009 (Phase 1/terminated, updated: February 2020) |
[194,195,196,197,198,199,200] |
| Charite University, Berlin, Germany | metastatic colorectal cancer |
NCT02519582 (Phase 2 /recruiting; updated: September 2018) |
[201] |
||
| genistein | Sofya Pintova | GSK3-β inhibitor |
colorectal cancer |
NCT01985763 (Phase 1; Phase 2/completed; updated: May 2019) |
[202,203] |
| resveratrol | University of California, Irvine | β-catenin/TCF interaction | colorectal cancer |
NCT00256334 (Phase 1/completed updated: June 2014) |
[204] |
| curcumin (dietary supplements: Mirtoselect®®®® & Meriva®®®®) |
Ente Ospedaliero Ospedali Galliera | β-catenin/TCF interaction | colorectal adenoma |
NCT01948661 (Phase not applicable, trial without FDA-defined phases /active, not recruiting; updated: August 2018) |
[205] |
EDDC, Experimental Drug Development Center.