Phase 2 Study of DKN-01 in Colorectal Cancer

Phase 2

Active, not recruiting

• Conditions: Colorectal Cancer; Colo-rectal Cancer; Colorectal Cancer Metastatic; Colorectal Adenocarcinoma
• Interventions: Drug: DKN-01; Drug: FOLFIRI; Drug: Bevacizumab; Drug: FOLFOX

• Registration Number: NCT05480306
• Lead Sponsor: Leap Therapeutics, Inc.

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.

Detailed Description

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.

In Parts A and B, approximately 200 evaluable adult advanced CRC patients with measurable disease (RECIST v1.1) who have radiographically progressed during or following 1 line of systemic treatment will be enrolled in the study.

The study consists of a Screening Period, a Treatment Period, a Safety Follow-up Period (SFUP) and a Long-Term Follow-up Period (LTFU). Patients will be followed in the SFUP for approximately 30 days (+7 days) after the last administration of study drug and then enter the LTFU period to be followed for survival and subsequent therapies. Additionally, patients that ended study treatment for a reason unrelated to progressive disease \[PD\] will also be followed for disease progression in the LTFU period.

Study Timeline

• Study First Submitted: 2022-07-21
• Study First Submitted QC: 2022-07-27
• Study First Posted: 2022-07-29
• Study Start: 2022-08-30
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-26
• Last Update Posted: 2025-04-02
• Primary Completion: 2025-10-31
• Study Completion: 2025-10-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 188

Inclusion Criteria

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

1. Disease progression following first-line systemic therapy with any fluoropyrimidine-based regimen for advanced disease (except FOLFOXIRI, see exclusion criteria).

   • 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.

2. Able to provide written informed consent for any study specific procedures.

3. One or more tumors measurable on radiographic imaging as defined by RECIST 1.1

4. Sufficient tumor tissue for mandatory pre-treatment evaluation (fresh biopsy [preferred], or archived tissue block specimen).

5. ECOG performance status ≤1 within 7 days of first dose of study drug. Acceptable liver, renal, hematologic, and coagulation function

6. 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

Exclusion Criteria

Patients meeting any of the following criteria are not eligible for study entry:

1. Diagnosis of Microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) and/or BRAF V600E mutation positive colorectal cancer.
2. 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.
3. Systemic anti-cancer therapy within 28 days prior to first dose of study drug.
4. Major surgery within 28 days prior to first dose of study drug.
5. Prior radiation therapy within 14 days prior to first dose of study drug.
6. Active leptomeningeal disease or uncontrolled brain metastases.
7. Any active cancer ≤ 2 years before first dose of study drug with the exception of cancer for this study.
8. New York Heart Association Class III or IV cardiac disease, myocardial infarction within the past 6 months, or unstable arrhythmia.
9. Fridericia-corrected QT interval (QTcF) > 470 msec (female) or history of congenital long QT syndrome.
10. Active, uncontrolled bacterial, viral, or fungal infections, within 14 days of study entry requiring systemic therapy.
11. Serious nonmalignant disease
12. Pregnant or nursing.
13. History of osteonecrosis of the hip or have evidence of structural bone abnormalities in the proximal femur on MRI scan that are symptomatic and clinically significant.
14. Known osteoblastic bony metastasis.
15. Major surgery 28 days prior to study entry.
16. Prior radiation therapy within 14 days prior to study entry.
17. Significant allergy to a pharmaceutical therapy that, in the opinion of the Investigator, poses an increased risk to the patient.
18. Active substance abuse.
19. Known dihydropyrimidine dehydrogenase deficiency.
20. Administration of a live vaccine within 28 days before first dose of study drug

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment	DKN-01	DKN-01 + FOLFIRI or FOLFOX + bevacizumab
Treatment	FOLFIRI	DKN-01 + FOLFIRI or FOLFOX + bevacizumab
Treatment	FOLFOX	DKN-01 + FOLFIRI or FOLFOX + bevacizumab
Control	FOLFIRI	FOLFIRI or FOLFOX + bevacizumab
Control	FOLFOX	FOLFIRI or FOLFOX + bevacizumab
Treatment	Bevacizumab	DKN-01 + FOLFIRI or FOLFOX + bevacizumab
Control	Bevacizumab	FOLFIRI or FOLFOX + bevacizumab

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS)	approximately 6 months	PFS, as determined by the Investigator per RECIST v1.1 of DKN-01 plus SOC versus SOC.

Secondary Outcome Measures

Name	Time	Method
Incidence of ≥Grade 3 related treatment-related adverse events (TRAEs).	approximately 6 months
Objective Response Rate (ORR)	approximately 6 months	ORR, as determined by the Investigator per RECIST v1.1 of DKN-01 plus SOC versus SOC
Overall Survival (OS)	approximately 6 months	OS with DKN-01 plus SOC versus SOC
Duration of Response (DoR)	approximately 6 months	DoR, as determined by the Investigator per RECIST v1.1 of DKN-01 plus SOC versus SOC

Trial Locations

Locations (37)

The University of Arizona Cancer Center; 🇺🇸 Tucson, Arizona, United States

UCLA; 🇺🇸 Los Angeles, California, United States

Florida Cancer Specialists & Research Institute (FCS); 🇺🇸 Cape Coral, Florida, United States

Florida Cancer Specialists & Research Institute; 🇺🇸 Wellington, Florida, United States

Miami Cancer Institute; 🇺🇸 Miami, Florida, United States

Hematology Oncology Clinic; 🇺🇸 Baton Rouge, Louisiana, United States

Center for Cancer and Blood Disorders; 🇺🇸 Bethesda, Maryland, United States

Oncology Hematology Associates - Springfield; 🇺🇸 Springfield, Missouri, United States

Northwell Health; 🇺🇸 Lake Success, New York, United States

New York University; 🇺🇸 New York, New York, United States

Cornell University; 🇺🇸 New York, New York, United States

Mount Sinai Medical Center - New York; 🇺🇸 New York, New York, United States

White Plains Hospital; 🇺🇸 White Plains, New York, United States

Messino Cancer Centers; 🇺🇸 Asheville, North Carolina, United States

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States

Wake Forest University; 🇺🇸 Winston-Salem, North Carolina, United States

Prisma Health Cancer Institute - Faris; 🇺🇸 Greenville, South Carolina, United States

Sanford Cancer Center; 🇺🇸 Sioux Falls, South Dakota, United States

Tennessee Oncology; 🇺🇸 Nashville, Tennessee, United States

SCRI Oncology Partners; 🇺🇸 Nashville, Tennessee, United States

MultiCare Tacoma General Hospital; 🇺🇸 Tacoma, Washington, United States

University of Wisconsin Hospital and Clinics; 🇺🇸 Madison, Wisconsin, United States

Universitaetsklinikum Hamburg-Eppendorf (UKE) - Universitaeres Cancer Center Hamburg (UCCH); 🇩🇪 Hamburg, Germany

Universitaetsklinikum Heidelberg (UKHD) - Nationales Centrum fuer Tumorerkrankungen Heidelberg (NCT); 🇩🇪 Heidelberg, Germany

SLK-Kliniken Heilbronn GmbH - Klinikum am Gesundbrunnen - Klinik fuer Innere Medizin III; 🇩🇪 Heilbronn, Germany

Gemeinschaftspraxis fuer Haematologie und Onkologie - Magdeburg; 🇩🇪 Magdeburg, Germany

Gachon University Gil Medical Center; 🇰🇷 Incheon, Korea, Republic of

Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz; 🇩🇪 Mainz, Germany

Dong-A University Medical Center; 🇰🇷 Busan, Korea, Republic of

Kyungpook National University Chilgok Hospital; 🇰🇷 Daegu, Korea, Republic of

Inha University Hospital; 🇰🇷 Incheon, Korea, Republic of

CHA University - Bundang CHA General Hospital; 🇰🇷 Seongnam-si, Korea, Republic of

Seoul National University Bundang Hospital; 🇰🇷 Seongnam-si, Korea, Republic of

Asan Medical Center; 🇰🇷 Seoul, Korea, Republic of

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of

Seoul National University Hospital; 🇰🇷 Seoul, Korea, Republic of

The Catholic University of Korea - St. Vincent's Hospital; 🇰🇷 Suwon, Korea, Republic of