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Table 1 Therapeutic strategies against Wnt/beta-catenin in current clinical development

From: Wnt/beta-catenin pathway: modulating anticancer immune response

Mechanism of action

Agent

Company name

Stage of clinical development

Status

Identifier

Details

PORCN inhibitor (blocks the secretion of Wnt ligands)

PORCN inhibitor

WNT974

Array Biopharma

Phase 1

Active, not recruiting

NCT02278133

In combination with LGX818 and cetuximab; patients with BRAF-mut mCRC and WNT pathway mutations

Phase 2

Withdrawn

NCT02649530

Patients with metastatic HNSCC; single-arm, non-randomized

LGK974

Novartis

Phase 1

Recruiting

NCT01351103

Documented BRAF mut for mCRC and pancreatic cancer; tumors of any histological origin with documented genetic alterations upstream in the Wnt signaling; trial was suspended due to unknown reasons

ETC-1922159

Phase 1a/1b

Recruiting

NCT02521844

Locally advanced or metastatic solid tumors

WNT-5a mimetic

Foxy-5

Wnt Research AB

Phase 1

Completed

NCT02020291

Metastatic breast, mCRC, or prostate cancer with loss of or reduced Wnt5a protein expression in IHC analysis

Phase 1

Recruiting

NCT02655952

Metastatic breast, mCRC, or prostate cancer with loss of or reduced Wnt5a protein expression in IHC analysis

Sam68 modulator: interferes with the alternative splicing of Tcf

CWP232291

JW Pharmaceutical

Phase 1

Completed

NCT01398462

Relapsed or refractory AML, CMML, MDS, or high-risk myelofibrosis

Phase1a/1b

Recruiting

NCT02426723

Relapsed or refractory MM

Wnt inhibitor

CGX1321

Curegenix Inc.

Phase 1

Recruiting

NCT02675946

Locally advanced or metastatic solid tumors

Inhibition of β-catenin recruitment through antagonizing its coactivator CBP (the binding protein of cAMP response element-binding protein CREB)

PRI-724

Prism Pharma Co.

Phase 1b

Completed

NCT01764477

Advanced or metastatic pancreatic adenocarcinoma, in combination with gemcitabine in the second line of treatment

Phase 1/2

Active, not recruiting

NCT01606579

Advanced myeloid malignancies

Randomized phase 2

Withdrawn

NCT02413853

Advanced mCRC, in combination with mFOLFOX6 + bevacizumab, in the first line of treatment

Phase 1a/1b

Terminated

NCT01302405

Phase 1a: any advanced neoplasm

Phase 1b: only patients with mCRC

Humanized monoclonal antibody OTSA101 against FZD10 and labeled with Y90

OTSA101

OncoTherapy Science

Phase 1

Active, not recruiting

NCT01469975

In patients with doxorubicin and ifosfamide-refractory synovial sarcoma

Monoclonal antibody against frizzled receptors

OMP-18R5 (Vantictumab)

OncoMed Pharmaceuticals

Phase1

Recruiting

NCT01973309

In patients with metastatic breast cancer in combination with paclitaxel

Humanized monoclonal antibody (Mab) with neutralizing activity against Dkk-1

DKN-01

Leap Therapeutics, Inc.

Phase 1

Recruiting

NCT02013154

In combination with paclitaxel in esophageal neoplasms, adenocarcinoma of the gastroesophageal junction, gastroesophageal cancer, squamous cell carcinoma, and gastric adenocarcinoma

Phase 1

Recruiting

NCT02375880

In combination with gemcitabine and Cisplatin in carcinoma of intrahepatic and extra-hepatic biliary systems, carcinoma of gallbladder, bile duct cancer, and cholangiocarcinoma

Antagonizes Wnt signaling through competes with the membrane-bound Fzd8 (decoy receptor)

OMP-54F28 (ipafricept)

OncoMed Pharmaceuticals

Phase 1b

Active, not recruiting

NCT02069145

In patients with locally advanced or metastatic hepatocellular cancer, in combination with sorafenib

Phase 1b

Recruiting

NCT02092363

In patients with recurrent platinum-sensitive ovarian cancer, in combination with paclitaxel and carboplatin

Phase 1b

Active, not recruiting

NCT02050178

In patients with untreated stage IV metastatic pancreatic cancer, in combination with gemcitabine and nab-paclitaxel

Phase 1

Completed

NCT01608867

Metastatic and unresectable refractory solid tumors

  1. Abbreviations: mCRC metastatic colorectal cancer, AML acute myeloid leukemia, CMML chronic myelomonocytic leukemia, MM multiple myeloma, Dkk1 Dickkopf-1, Y90 radioactive yttrium90