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

Sponsor
Leap Therapeutics, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT02013154
Collaborator
Merck Sharp & Dohme LLC (Industry)
151
Enrollment
10
Locations
7
Arms
80.3
Actual Duration (Months)
15.1
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease Intervention/Treatment Phase
Phase 1

Detailed Description

Part A is a Dose-Escalation Study in Participants with Relapsed or Refractory Esophageal Cancer or Gastro-Esophageal Junction Tumors. Parts B, C, D and E are expansion cohorts of Patients with Relapsed or Refractory Esophageal Cancer, Gastro-Esophageal Junction Tumors and Gastric Adenocarcinoma.

Part F is a Dose-Escalation and Expansion Cohorts with DKN-01 + Pembrolizumab in Patients with Recurrent or Metastatic Esophageal Cancer, Gastroesophageal Junction Cancer or Gastric Adenocarcinoma with Wnt Signaling Alterations.

Patients who are unable to receive paclitaxel or pembrolizumab for any reason will be allowed to receive single agent DKN-01 as part of a monotherapy substudy.

Study Design

Study Type:
Interventional
Actual Enrollment :
151 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
May 5, 2014
Actual Primary Completion Date :
Jul 19, 2019
Actual Study Completion Date :
Jan 11, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Part A: DKN-01 (Dose Escalation)

Escalating dose of 150 milligrams (mg) up to 300 mg of DKN-01 administered on days 1 and 15 and 80 milligrams per meter squared of body surface area (mg/m2) of paclitaxel administered on days 1,8,15, and 22

Drug: DKN-01
Administered by IV infusion

Drug: Paclitaxel
Administered by IV infusion
Other Names:
  • Taxol

    		•
    Experimental: Part B: DKN-01 (Dose Confirmation)

    Dose of DKN-01 determined in Part A will be administered to esophageal or gastro-esophageal junction cancer patients on Days 1 and 15 and 80 mg/m2 of paclitaxel administered on Days 1,8,15,and 22

    Drug: DKN-01
    Administered by IV infusion

    Drug: Paclitaxel
    Administered by IV infusion
    Other Names:
  • Taxol

    		•
    Experimental: Part C: DKN-01 (Cohort Expansion)

    Dose of DKN-01 determined in Part A will be administered to esophageal or gastro-esophageal junction adenocarcinoma patients on Days 1 and 15 and 80 mg/m2 of paclitaxel administered on Days 1,8,15,and 22

    Drug: DKN-01
    Administered by IV infusion

    Drug: Paclitaxel
    Administered by IV infusion
    Other Names:
  • Taxol

    		•
    Experimental: Part D: DKN-01 (Cohort Expansion)

    Dose of DKN-01 determined in Part A will be administered to esophageal squamous cell cancer patients on Days 1 and 15 and 80 mg/m2 of paclitaxel administered on Days 1,8,15,and 22

    Drug: DKN-01
    Administered by IV infusion

    Drug: Paclitaxel
    Administered by IV infusion
    Other Names:
  • Taxol

    		•
    Experimental: DKN-01 Monotherapy Substudy

    Dose of DKN-01 determined in Part A will be administered to esophageal or gastro-esophageal junction cancer patients on Days 1 and 15

    Drug: DKN-01
    Administered by IV infusion
    Experimental: Part E: DKN-01 (Cohort Expansion)

    Dose of DKN-01 determined in Part A will be administered to gastric adenocarcinoma with Wnt signaling alteration cancer patients on Days 1 and 15 and 80 mg/m2 of paclitaxel administered on Days 1,8,15,and 22

    Drug: DKN-01
    Administered by IV infusion

    Drug: Paclitaxel
    Administered by IV infusion
    Other Names:
  • Taxol

    		•
    Experimental: Part F DKN-01 (Dose Escalation+Expansion)

    Escalating dose on 150mg up to 300 mg of DKN-01 administered to patients with recurrent or metastatic esophageal cancer, gastroesophageal junction cancer or gastric adenocarcinoma with Wnt signaling alterations on days 1 and 15 and 200 mg of pembrolizumab administered on day 1 of a 21 day cycle

    Drug: DKN-01
    Administered by IV infusion

    Drug: Pembrolizumab
    Administered by IV infusion
    Other Names:
  • Keytruda

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of subjects with dose limiting toxicities in Study Parts A and F which will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v4.03 [Baseline to End of cycle 1 (Part A cycle is 28 days and Part F cycle is 21 days)]

    2. Number of subjects with adverse drug reactions and toxicities as evaluated by NCI CTCAE v4.03 of DKN-01 as monotherapy or in combination with paclitaxel or pembrolizumab [Baseline until 30 days after last dose of study drug as assessed at a minimum of every 2 weeks]

    Secondary Outcome Measures

    1. Clinical response to treatment [Baseline to study completion (approximately 3 months)]

    2. Objective Response Rate (ORR) [Baseline to study completion (approximately 3 months)]

    3. Objective Disease Control Rate (ODCR) [Baseline to study completion (approximately 3 months)]

    4. Duration of Response (DoR) [Baseline to study completion (approximately 3 months)]

    5. Duration of CR (DoCR) [Baseline to study completion (approximately 3 months)]

    6. Overall Survival (OS) [Baseline to study completion (approximately 3 months)]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Cedars Sinai Medical Care Foundation Los Angeles California United States 90025
    2 Smilow Cancer Hospital at Yale - New Haven New Haven Connecticut United States 06520
    3 Northwestern University Chicago Illinois United States 60611
    4 Dana Farber Cancer Institute Boston Massachusetts United States 02215
    5 Massachusetts General Hospital Boston Massachusetts United States 02215
    6 Duke University Durham North Carolina United States 27710
    7 Tennessee Oncology / Sarah Cannon Research Institute Nashville Tennessee United States 37203
    8 Vanderbilt University / VICC Nashville Tennessee United States 37232
    9 Mary Crowley Cancer Center Dallas Texas United States 75251
    10 CTRC @ The University of Texas Health Science Center at San Antonio San Antonio Texas United States 78229

    Sponsors and Collaborators

    • Leap Therapeutics, Inc.
    • Merck Sharp & Dohme LLC

    Investigators

    • Study Director: Cyndi Sirard, MD, Leap Therapeutics, Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Leap Therapeutics, Inc.
    ClinicalTrials.gov Identifier:
    NCT02013154
    Other Study ID Numbers:
    • DEK-DKK1-P102
    • DKN-01
    • LY2812176
    • KEYNOTE-731
    First Posted:
    Dec 17, 2013
    Last Update Posted:
    Sep 10, 2021
    Last Verified:
    Sep 1, 2021
    Additional relevant MeSH terms:
    Adenocarcinoma
    Esophageal Neoplasms
    Paclitaxel
    Pembrolizumab

    Study Results

    No Results Posted as of Sep 10, 2021