A Study of DKN-01 in Combination With Paclitaxel or Pembrolizumab

NCT02013154 | Completed Phase 1

• 4 other identifiers: DEK-DKK1-P102DKN-01LY2812176KEYNOTE-731
• Study Type: interventional
• Target: 151
• Locations: 1 country
• Sites: 10

Brief Summary

A study to evaluate the safety and tolerability of DKN-01 in combination with weekly paclitaxel or pembrolizumab in participants with relapsed or refractory Esophagogastric Malignancies

Conditions

Esophageal Neoplasms; Adenocarcinoma of the Gastroesophageal Junction; Gastroesophageal Cancer; Squamous Cell Carcinoma; Gastric Adenocarcinoma

Outcome Measures

Primary Outcomes (2)

• Number of subjects with dose limiting toxicities in each treatment arm

  Baseline to End of Cycle 1 (each cycle is 28 days, except each cycle is 21 days when DKN-01 is administered with pembrolizumab)

• Number of subjects with treatment emergent adverse events related to study treatment (DKN-01 as monotherapy or in combination with paclitaxel or pembrolizumab)

  Baseline until 30 days after last dose of study drug

Secondary Outcomes (4)

• Objective Response Rate (ORR)

  Baseline to study completion (approximately 3 months)

• Duration of Response (DoR)

  Baseline to study completion (approximately 3 months)

• Overall Survival (OS)

  Baseline to study completion (approximately 3 months)

• Progression Free Survival (PFS)

  Baseline to study completion (approximately 3 months)

Study Arms (5)

DKN-01 150 mg plus paclitaxel

EXPERIMENTAL

DKN-01 150 mg administered on Days 1 and 15 and paclitaxel 80 mg per meter squared of body surface area (mg/m2) administered on Days 1, 8, 15, and 22

Drug: DKN-01 150 mg; Drug: Paclitaxel

DKN-01 300 mg plus paclitaxel

EXPERIMENTAL

DKN-01 300 mg administered on Days 1 and 15 and paclitaxel 80 mg per meter squared of body surface area (mg/m2) administered on Days 1, 8, 15, and 22

Drug: Paclitaxel; Drug: DKN-01 300 mg

DKN-01 150 mg plus pembrolizumab

EXPERIMENTAL

DKN-01 150 mg administered on Days 1 and 15 and pembrolizumab 200 mg administered on Day 1

Drug: DKN-01 150 mg; Drug: Pembrolizumab

DKN-01 300 mg plus pembrolizumab

EXPERIMENTAL

DKN-01 300 mg administered on Days 1 and 15 and pembrolizumab 200 mg administered on Day 1

Drug: Pembrolizumab; Drug: DKN-01 300 mg

DKN-01 300 mg monotherapy

EXPERIMENTAL

DKN-01 300 mg administered on Days 1 and 15

Drug: DKN-01 300 mg

Interventions

DKN-01 150 mg DRUG

Administered by IV infusion

DKN-01 150 mg plus paclitaxel; DKN-01 150 mg plus pembrolizumab

Paclitaxel DRUG

Administered by IV infusion

Also known as: Taxol

DKN-01 150 mg plus paclitaxel; DKN-01 300 mg plus paclitaxel

Pembrolizumab DRUG

Administered by IV infusion

Also known as: Keytruda

DKN-01 150 mg plus pembrolizumab; DKN-01 300 mg plus pembrolizumab

DKN-01 300 mg DRUG

Administered by IV infusion

DKN-01 300 mg monotherapy; DKN-01 300 mg plus paclitaxel; DKN-01 300 mg plus pembrolizumab

Eligibility Criteria

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

You may qualify if:

• In advanced esophagogastric malignancies:
• Participants with histologically confirmed recurrent or metastatic esophageal or gastro-esophageal junction squamous cell or adenocarcinoma or gastric adenocarcinoma with Wnt Signaling Alterations
• Participants must be refractory or intolerant to at least one prior therapy(ies) for metastatic or locally advanced disease
• If prior therapy consisted of palliative chemoradiation therapy, it will be considered one line of therapy
• Prior treatment with paclitaxel as part of a definitive therapy regimen is acceptable. Patients who are unable to receive paclitaxel for any reason will be allowed to receive DKN-01 as a single agent.
• Prior treatment anti- programmed death-1 (PD-1)/ anti-PD-ligand 1 (PD-L1) monoclonal antibody (mAb) is permitted in patients provided the patient's disease is primary refractory, and the patient is not intolerant of pembrolizumab. Patients who are not eligible to receive pembrolizumab will be allowed to receive single agent DKN-01
• Tumor tissue for mandatory evaluation
• Must have one or more tumors measurable on radiographic imaging as defined by the Response Evaluation Criteria in Solid Tumors (RECIST). Patients with evaluable but not measurable disease per RECIST criteria may be enrolled with the approval of the medical monitor.
• Must be ≥18 years of age
• Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale. A performance status of 2 on the ECOG scale may be entered upon the review and approval of the medical monitor
• Disease-free of active second/secondary or prior malignancies for equal to or over 2 years with the exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in-situ" of the cervix or breast
• Acceptable liver, renal, hematologic and coagulation function
• For men and women of child-producing potential, the use of effective contraceptive methods during the study and for 6 months following the last dose of study drug

You may not qualify if:

• New York Heart Association Class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia
• Fridericia-corrected QT interval (QTcF) \> 470 msec (female) or \> 450 (male), or history of congenital long QT syndrome.
• Active, uncontrolled bacterial, viral, or fungal infections, within 7 days of study entry requiring systemic therapy
• Known to be human immunodeficiency virus (HIV) positive, have hepatitis B surface antigen (HBSAg), or hepatitis C antibodies (HCAb) unless HCV RNA is undetected/negative.
• Serious nonmalignant disease
• Pregnant or nursing women
• 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.
• Systemic central nervous system (CNS) malignancy or metastasis.
• Clinically significant peripheral neuropathy at the time of study entry. Patients with pre-existing peripheral neuropathy will be allowed to receive single agent DKN-01
• Known osteoblastic bony metastasis
• History of known or suspected autoimmune disease with the specific exceptions of vitiligo, atopic dermatitis, or psoriasis not requiring systemic treatment.
• Clinically-significant gastrointestinal disorders, such as perforation, gastrointestinal bleeding, or diverticulitis.
• Active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Treatment with surgery or chemotherapy within 21 days prior to study entry (42 days for nitrosoureas or mitomycin C)
• Treatment with low dose chemotherapy concurrent with radiation within 14 days prior to study entry

Sponsors & Collaborators

• Leap Therapeutics, Inc.: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (10)

Cedars Sinai Medical Care Foundation

Los Angeles, California, 90025, United States

Location

Smilow Cancer Hospital at Yale - New Haven

New Haven, Connecticut, 06520, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02215, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Tennessee Oncology / Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Vanderbilt University / VICC

Nashville, Tennessee, 37232, United States

Location

Mary Crowley Cancer Center

Dallas, Texas, 75251, United States

Location

CTRC @ The University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Esophageal Neoplasms; Carcinoma, Squamous Cell

Interventions

Paclitaxel; pembrolizumab

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Squamous Cell

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Cyndi Sirard, MD

  Leap Therapeutics, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2013
• First Posted: December 17, 2013
• Study Start: May 5, 2014
• Primary Completion: July 19, 2019
• Study Completion: January 11, 2021
• Last Updated: August 3, 2025

Record last verified: 2025-07

Locations

US (10)