Phase 2 Study of DKN-01 in Colorectal Cancer

NCT05480306 | Completed Phase 2 FDA Drug

• 1 other identifier: DEK-DKK1-P207
• Study Type: interventional
• Target: 188
• Locations: 3 countries
• Sites: 40

Brief Summary

This is a Phase 2 randomized, open-label, two-part, multicenter study with a safety run-in to evaluate efficacy and safety of DKN-01 plus FOLFIRI/FOLFOX and bevacizumab versus standard of care (SOC) \[FOLFIRI/FOLFOX and bevacizumab\] as second-line treatment of advanced CRC patients.

Conditions

Colo-rectal Cancer; Colorectal Adenocarcinoma; Colorectal Cancer Metastatic

Keywords

DKK1; colorectal cancer; DKN-01

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  PFS, as determined by the Investigator per RECIST v1.1 of DKN-01 plus SOC versus SOC.

  approximately 6 months

Secondary Outcomes (4)

• Objective Response Rate (ORR)

  approximately 6 months

• Duration of Response (DoR)

  approximately 6 months

• Overall Survival (OS)

  approximately 6 months

• Incidence of ≥Grade 3 related treatment-related adverse events (TRAEs).

  approximately 6 months

Other Outcomes (6)

• Duration of Complete Response (DoCR)

  approximately 6 months

• Duration of clinical benefit (DoCB)

  approximately 6 months

• Durable clinical benefit (DCB)

  approximately 6 months

Study Arms (2)

Treatment

EXPERIMENTAL

DKN-01 + FOLFIRI or FOLFOX + bevacizumab

Drug: DKN-01; Drug: FOLFIRI; Drug: Bevacizumab; Drug: FOLFOX

Control

ACTIVE COMPARATOR

FOLFIRI or FOLFOX + bevacizumab

Drug: FOLFIRI; Drug: Bevacizumab; Drug: FOLFOX

Interventions

DKN-01 DRUG

30 minute IV infusion (400mg) every two weeks with an additional loading dose in the first cycle of treatment

Also known as: LY2812176

Treatment

FOLFIRI DRUG

90-min IV infusion of irinotecan, leucovorin, and fluorouracil followed by a continuous 46-hour infusion of fluorouracil every two weeks

Control; Treatment

Bevacizumab DRUG

90-min IV infusion (5mg)

Control; Treatment

FOLFOX DRUG

2 hour IV infusion of oxaliplatin, folinic acid, and fluorouracil followed by a continuous 46-hour infusion of fluorouracil every two weeks

Control; Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients meeting all of the following criteria will be considered eligible for study entry:

You may not qualify if:

• Patients may have received prior neoadjuvant or adjuvant therapy which could have included irinotecan or oxaliplatin. If progression has occurred within 12 months from last dose of neoadjuvant or adjuvant treatment, this regimen will be considered as the one line of systemic therapy for advanced disease.
• If assigned to receive FOLFIRI, patient may have received no prior irinotecan as part of first-line systemic therapy.
• If assigned to receive FOLFOX, patient may have received no prior oxaliplatin as part of first line systemic therapy.
• Prior treatment with an anti-VEGF or anti-EGFR therapy is allowed as first-line and/or maintenance systemic therapy.
• Able to provide written informed consent for any study specific procedures.
• One or more tumors measurable on radiographic imaging as defined by RECIST 1.1
• Sufficient tumor tissue for mandatory pre-treatment evaluation (fresh biopsy \[preferred\], or archived tissue block specimen).
• ECOG performance status ≤1 within 7 days of first dose of study drug. Acceptable liver, renal, hematologic, and coagulation function
• Females of childbearing potential and male partners of female patients must agree to use adequate contraception during the study and for 6 months after their last dose of study drug
• Patients meeting any of the following criteria are not eligible for study entry:
• Diagnosis of Microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) and/or BRAF V600E mutation positive colorectal cancer.
• Prior therapy with an anti-DKK1, FOLFOXIRI, PD-1, anti-PD-L1, anti-PD-L-2 or any other antibody or drug specifically targeting T-cell co-stimulation or coinhibitory checkpoint.
• Systemic anti-cancer therapy within 28 days prior to first dose of study drug.
• Major surgery within 28 days prior to first dose of study drug.
• Prior radiation therapy within 14 days prior to first dose of study drug.

Sponsors & Collaborators

• Leap Therapeutics, Inc.: lead

Study Sites (40)

The University of Arizona Cancer Center

Tucson, Arizona, 85719, United States

Location

UCLA

Los Angeles, California, 90404, United States

Location

Florida Cancer Specialists & Research Institute (FCS)

Cape Coral, Florida, 33909, United States

Location

Florida Cancer Specialists & Research Institute

Fleming Island, Florida, 32003, United States

Location

Florida Cancer Specialists & Research Institute

Gainesville, Florida, 32605, United States

Location

Miami Cancer Institute

Miami, Florida, 33176, United States

Location

Florida Cancer Specialists & Research Institute

Wellington, Florida, 33414, United States

Location

Hematology Oncology Clinic

Baton Rouge, Louisiana, 70809, United States

Location

Center for Cancer and Blood Disorders

Bethesda, Maryland, 20817, United States

Location

Oncology Hematology Associates - Springfield

Springfield, Missouri, 65807, United States

Location

Northwell Health

Lake Success, New York, 11020, United States

Location

New York University

New York, New York, 10016, United States

Location

Cornell University

New York, New York, 10021, United States

Location

Mount Sinai Medical Center - New York

New York, New York, 10029, United States

Location

White Plains Hospital

White Plains, New York, 10601, United States

Location

Messino Cancer Centers

Asheville, North Carolina, 28806, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Wake Forest University

Winston-Salem, North Carolina, 27157, United States

Location

Prisma Health Cancer Institute - Faris

Greenville, South Carolina, 29605, United States

Location

Sanford Cancer Center

Sioux Falls, South Dakota, 57104, United States

Location

Tennessee Oncology

Chattanooga, Tennessee, 37404, United States

Location

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

MultiCare Tacoma General Hospital

Tacoma, Washington, 98405, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

Universitaetsklinikum Hamburg-Eppendorf (UKE) - Universitaeres Cancer Center Hamburg (UCCH)

Hamburg, Germany

Location

Universitaetsklinikum Heidelberg (UKHD) - Nationales Centrum fuer Tumorerkrankungen Heidelberg (NCT)

Heidelberg, Germany

Location

SLK-Kliniken Heilbronn GmbH - Klinikum am Gesundbrunnen - Klinik fuer Innere Medizin III

Heilbronn, Germany

Location

Gemeinschaftspraxis fuer Haematologie und Onkologie - Magdeburg

Magdeburg, Germany

Location

Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz

Mainz, Germany

Location

Dong-A University Medical Center

Busan, South Korea

Location

Kyungpook National University Chilgok Hospital

Daegu, South Korea

Location

Gachon University Gil Medical Center

Incheon, South Korea

Location

Inha University Hospital

Incheon, South Korea

Location

CHA University - Bundang CHA General Hospital

Seongnam-si, South Korea

Location

Seoul National University Bundang Hospital

Seongnam-si, South Korea

Location

Asan Medical Center

Seoul, South Korea

Location

Samsung Medical Center

Seoul, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

The Catholic University of Korea - St. Vincent's Hospital

Suwon, South Korea

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Colonic Neoplasms

Interventions

IFL protocol; Bevacizumab; Folfox protocol

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Cynthia Sirard

  Leap Therapeutics, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 21, 2022
• First Posted: July 29, 2022
• Study Start: August 30, 2022
• Primary Completion: July 10, 2025
• Study Completion: July 10, 2025
• Last Updated: August 3, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

KR (10); DE (5); US (25)