Table 1.
Wnt Pathway Inhibitors in Cancer Clinical Trials
| Drug Identifier | Mode of Action | Trial Identifier | Regimen | Cancer Indication | Trial Phase | Study Status or Clinical Results |
|---|---|---|---|---|---|---|
| OMP-54F28 (Ipafricept) | Fzd8-Fc Decoy receptor | NCT01608867 | Monotherapy | Solid tumors | 1 | Dysgeusia and fragility fractures observed. Best response was SD (Jimeno et al., 2017) |
| NCT02092363 | In combination with paclitaxel and carboplatin | ovarian cancer; | 1 | ORR 76%, comparable with historical data. Development in ovarian stopped due to bone toxicity (Moore et al., 2019) | ||
| NCT02069145 | In combination with sorafenib (HCC) | Hepatocellular carcinoma | 1 | Study completed, no results reported | ||
| NCT02050178 | In combination with Gemcitabine and Nab-paclitaxel | 1L pancreatic ductal adenocarcinoma | 1 | 35% PR, 46% SD. Study terminated due to bone toxicity (Dotan et al., 2020) | ||
| OMP18R5 (Vantictumab) | Anti-Fzd7 antibody, also neutralizes binding to Wnts to Fzd 1, 2, 5,8 | NCT01345201 | Monotherapy | Solid tumors | 1 | Study completed, no results reported |
| NCT01957007 | In combination with docetaxel | Previously treated Non-small cell lung cancer; | 1 | Study completed, no results reported | ||
| NCT02005315 | In combination with Nab-Paclitaxel and Gemcitabine | 1L pancreatic ductal adenocarcinoma | 1 | ORR 42%. Study terminated due to bone toxicity (Davis et al., 2020) | ||
| NCT01973309 | In combination with paclitaxel | Locally recurrent/ metastatic breast cancer | 1 | ORR 31%. Wnt pathway gene signature associated with longer PFS/OS. Bone fractures observed (Diamond et al., 2020) | ||
| NCT04176016 | monotherapy | Synovial sarcoma | Recruiting | |||
| OTSA101 | Yttrium90 radiolabelled Anti-Fzd10 antibody | NCT01469975 | monotherapy | Synovial sarcoma | 1 | Most common adverse events were hematologic disorders. SD in 3/8 patients (Giraudet et al., 2018) |
| NCT04176016 | monotherapy | Synovial sarcoma | 1 | Recruiting | ||
| OMP131R10 | Anti-R-spondin3 antibody | NCT02482441 | With or without FOLFIRI | RSPO3 biomarker-positive metastatic colorectal cancer | 1 | Best response was SD in 3/7 patients treated with chemo combination (Bendell et al., 2016) |
| Foxy-5 | Wnt5a mimetic | NCT02655952 | monotherapy | Breast cancer; colorectal cancer; prostate cancer | 1 | Completed. No efficacy data reported |
| NCT02020291 | monotherapy | Breast cancer; colorectal cancer; prostate cancer | 1 | Completed. No efficacy data reported | ||
| NCT03883802 | As Neoadjuvant with surgery+FOLFOX | Wnt5a low colon cancer | 2 | Recruiting | ||
| PRI-724 | Inhibitor of TCF-CBP interaction | NCT01302405 | Monotherapy | Advanced solid cancers | 1 | No responses reported (El-Khoueiry et al., 2013) |
| NCT01606579 | Monotherapy or in combination with dasatinib, or cytarabine | Acute and chronic myelogenous leukaemia | 1/2 | Completed. No results reported | ||
| NCT01764477 | In combination with Gemcitabine | Advanced/metastatic pancreatic adenocarcinoma |
1 | Rest response was SD in 8/20 patients (Ko et al., 2016) | ||
| CWP232291 | Induces degradation of beta catenin. Molecular target not defined | NCT01398462 | Monotherapy | Acute Myeloid Leukaemia | 1 | ORR 3% GI side-effects were most common (Lee et al., 2020) |
| NCT03055286 | In combination with cytabarine | Acute Myeloid Leukaemia | 1/2 | Active, not recruiting | ||
| NCT02426723 | Monotherapy or in combination With Lenalidomide and Dexamethasone | Relapsed/refractory multiple myeloma | 1 | Completed. 4/14 patients with response, 4 had stable disease (Manasanch et al., 2017) | ||
| SM04755 | Small molecule Wnt inhibitor | NCT02191761 | Monotherapy | Advanced CRC, gastric, HCC and pancreatic cancer | 1 | Completed. No results reported |
| Cirmtuzumab | Anti-ROR1 antibody | NCT05156905 | In combination with docetaxel | Metastatic castration resistant prostate cancer | 2 | Not yet recruiting |
Source: Clinicaltrials.gov. Data collected on 10th January 2022. Withdrawn trial or trials terminated early are not included. Dkk blocking antibodies such as DKN01 and BHQ880 were not included due to observed effects on other (non Wnt) pathways.