Esophageal Cancer Clinical Trial
A Study of DKN-01 in Combination With Paclitaxel or Pembrolizumab
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
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.
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 (immunotherapy-drugs-are-boosting-survival/" >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
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
Check Your Eligibility
Let’s see if you might be eligible for this study.
What is your age and gender ?
There are 9 Locations for this study
Los Angeles California, 90025, United States
New Haven Connecticut, 06520, United States
Chicago Illinois, 60611, United States
Boston Massachusetts, 02215, United States
Boston Massachusetts, 02215, United States
Durham North Carolina, 27710, United States
Nashville Tennessee, 37203, United States
Nashville Tennessee, 37232, United States
Dallas Texas, 75251, United States
San Antonio Texas, 78229, United States
How clear is this clinincal trial information?
Introducing, the Journey Bar
Use this bar to access information about the steps in your cancer journey.