A Study of DKN-01 in Combination With Paclitaxel or Pembrolizumab (P102)

A Multi-part, Phase 1, Multi-center, Open-label Study of DKN-01 as a Monotherapy or in Combination With Paclitaxel or Pembrolizumab in Patients With Relapsed or Refractory Esophagogastric Malignancies

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

Study Overview

• Status: Completed
• Conditions: Esophageal Neoplasms; Gastric Adenocarcinoma; Adenocarcinoma of the Gastroesophageal Junction; Squamous Cell Carcinoma; Gastroesophageal Cancer
• Intervention / Treatment: Drug: Paclitaxel; Drug: Pembrolizumab; Drug: DKN-01 150 mg; Drug: DKN-01 300 mg

Detailed Description

This is a dose-escalating, open-label study conducted in multiple parts (Part A dose-escalation, Parts B-F expansion cohorts, and a monotherapy substudy). Parts A-E (DKN-01 plus paclitaxel) and the DKN-01 monotherapy substudy includes 28-day cycle treatment cycles; Part F (DKN-01 plus pembrolizumab) includes 21-day treatment cycles. Depending on their cancer type, subjects with histologically confirmed recurrent or refractory esophageal, gastro-esophageal junction tumors, or gastric adenocarcinoma will be enrolled in each study part to receive DKN-01 150 mg or 300 mg in combination with paclitaxel or pembrolizumab. Subjects who are unable to receive paclitaxel or pembrolizumab for any reason are allowed to receive single agent DKN-01 300 mg as part of a monotherapy substudy. Results are reported by treatment group, irrespective of the study part in which the subject was enrolled.

• Study Type: Interventional
• Enrollment (Actual): 151
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90025
      • Cedars Sinai Medical Care Foundation
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Smilow Cancer Hospital at Yale - New Haven
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
    • Boston, Massachusetts, United States, 02215
      • Massachusetts General Hospital
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology / Sarah Cannon Research Institute
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University / VICC
  • Texas
    • Dallas, Texas, United States, 75251
      • Mary Crowley Cancer Center
    • San Antonio, Texas, United States, 78229
      • CTRC @ The University of Texas Health Science Center at San Antonio

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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

Exclusion Criteria:

• 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
• Treatment with radiation therapy within 14 days prior to study entry
• Treatment with any other investigational agent within 30 days prior to study entry
• Previously treated with an anti-DKK-1 therapy
• Participants who have a history of hypersensitivity reactions to TAXOL® or other drugs formulated in Cremophor® EL (polyoxyethylated castor oil). Patients who exhibit these hypersensitivities will be eligible to receive single agent DKN-01.
• Significant allergy to a pharmaceutical therapy that, in the opinion of the investigator, poses an increased risk to the participant
• Treatment with corticosteroids (≥ 10 mg per day prednisone or equivalent) or other immune suppressive drugs within the 14 days prior to study entry
• Active substance abuse
• Receipt of any live vaccines within 30 days before the first dose of study treatment and while participating in the study
• History of (non-infectious) pneumonitis that required steroids or current pneumonitis
• History of interstitial lung disease
• Intolerance or severe hypersensitivity (≥Grade 3) to pembrolizumab and/or of its excipients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DKN-01 150 mg plus paclitaxel; 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: Paclitaxel; Administered by IV infusion; Other Names: Taxol; Drug: DKN-01 150 mg; Administered by IV infusion
Experimental: DKN-01 300 mg plus paclitaxel; 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; Administered by IV infusion; Other Names: Taxol; Drug: DKN-01 300 mg; Administered by IV infusion
Experimental: DKN-01 150 mg plus pembrolizumab; DKN-01 150 mg administered on Days 1 and 15 and pembrolizumab 200 mg administered on Day 1	Drug: Pembrolizumab; Administered by IV infusion; Other Names: Keytruda; Drug: DKN-01 150 mg; Administered by IV infusion
Experimental: DKN-01 300 mg plus pembrolizumab; DKN-01 300 mg administered on Days 1 and 15 and pembrolizumab 200 mg administered on Day 1	Drug: Pembrolizumab; Administered by IV infusion; Other Names: Keytruda; Drug: DKN-01 300 mg; Administered by IV infusion
Experimental: DKN-01 300 mg monotherapy; DKN-01 300 mg administered on Days 1 and 15	Drug: DKN-01 300 mg; Administered by IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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)

Collaborators and Investigators

• Sponsor: Leap Therapeutics, Inc.
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Study Director: Cyndi Sirard, MD, Leap Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2014
• Primary Completion (Actual): July 19, 2019
• Study Completion (Actual): January 11, 2021

Study Registration Dates

• First Submitted: December 11, 2013
• First Submitted That Met QC Criteria: December 11, 2013
• First Posted (Estimated): December 17, 2013

Study Record Updates

• Last Update Posted (Actual): August 3, 2025
• Last Update Submitted That Met QC Criteria: July 30, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Esophageal Diseases; Carcinoma; Esophageal Neoplasms; Adenocarcinoma; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Pembrolizumab; Paclitaxel
• Other Study ID Numbers: DEK-DKK1-P102; DKN-01; LY2812176 (Healthcare Pharmaceuticals); KEYNOTE-731 (Other Identifier: Merck)