Official Title
Expanded Access Use of DKN-01 for the Treatment of Advanced Solid Tumors
Brief Summary

An Expanded Access Protocol for use of DKN-01 for the treatment of advanced solid tumors.

Detailed Description

This is a intermediate-size Expanded Access Protocol (EAP). Patients who were receiving
DKN-01 in a parent study at the time of completion of the parent study, and are, in the
opinion of the Investigator and Sponsor, suitable candidates for continued study drug
treatment are eligible for participation in the current EAP. In this EAP, previously
treated patients will receive DKN-01 at the same dose and schedule as at the time of
completion of the parent study. Furthermore, patients who received DKN-01 in combination
in the parent study will continue to receive the same combination agent at the same dose
and schedule in the EAP.

DKN-01 naïve patients, with advanced solid tumors not eligible for enrollment to a DKN-01
clinical study but whom, in the opinion of the treating oncologist, would potentially
receive benefit from treatment with DKN-01 while it is an investigational drug may be
eligible for enrollment in this EAP. Eligible DKN-01 naïve patients with Wnt activating
mutations will receive DKN-01 as monotherapy, administered intravenously on Day 1 of each
21-day cycle at a dose of 600 mg, with a loading dose of 600 mg of DKN-01 administered on
Day 15 of Cycle 1 only.

Available
Intermediate-size Population
Esophageal Neoplasm
Adenocarcinoma of the Gastroesophageal Junction
GastroEsophageal Cancer
Squamous Cell Carcinoma
Gastric Adenocarcinoma
Endometrial Cancer
Uterine Cancer
Ovarian Cancer
Carcinosarcoma
Gastric Cancer

Drug: DKN-01

Administered by IV infusion

Eligibility Criteria

Inclusion Criteria:

- Cytologically or histologically confirmed advanced solid tumors that are inoperable,
locally advanced, metastatic, or recurrent, with no standard of care treatment
options, and not eligible for enrollment to a DKN-01 clinical study, may be treated
with DKN-01 in this study if in the opinion of the treating oncologist, would
potentially receive benefit from treatment with DKN-01 while it is an
investigational drug

- Prior documentation of a known Wnt activating mutation by a CLIA-accredited
laboratory. Wnt activating mutations: CTNNB1, APC, AXIN1/2, RNF43, ZNRD3, RSPO2,
RSPO3

- ECOG performance status (PS) of ≤ 2 (Medical Monitor's approval is needed for
enrolling a patient with PS of 2).

- Laboratory values:

1. Total bilirubin ≤ 2.0 times upper limit of normal (ULN). Total bilirubin must
be < 3 X ULN for patients with Gilbert's syndrome.

2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 X ULN
(if liver metastases are present, then ≤ 5 X ULN is allowed).

3. Serum creatinine ≤ 1.5 X ULN.

4. Neutrophil absolute count ≥ 1,500/mm3 (≥1.5 X 109/L).

5. Platelet count ≥ 75,000/mm3 (≥100 X 109/L).

6. Hemoglobin ≥ 9g/dL (transfusion within 30 days of screening is permitted).

Exclusion Criteria:

- Major surgery within 4 weeks of first dose of study drug.

- Toxicities (as a result of prior anticancer therapy) that have not recovered to
baseline or stabilized, except for AEs not considered a likely safety risk (e.g.,
alopecia, neuropathy and specific laboratory abnormalities).

- Any of the following cardiovascular risk factors:

1. Pulmonary embolism within 28 days before first dose of study drug.

2. Any history of acute myocardial infarction within 6 months before first dose of
study drug.

3. Uncontrolled hypertension that cannot be managed by standard anti-hypertension
medications within 28 days before first dose of study drug.

- Severe chronic or active infections requiring systemic antibacterial, antifungal or
antiviral therapy, including tuberculosis infection within 14 days of first dose of
study drug.

- Active brain metastases. Patients are eligible if brain metastases are adequately
treated, and patients are neurologically stable for at least 2 weeks prior to
enrolment without the use of corticosteroids or are on a stable or decreasing dose
of ≤ 10mg daily prednisone (or equivalent).

Eligibility Gender
All
Eligibility Age
Minimum: 18 Years ~ Maximum: N/A
Countries
United States
Locations

University of Alabama
Birmingham, Alabama, United States

Cedars Sinai Medical Care Foundation
Los Angeles, California, United States

Northwestern University
Chicago, Illinois, United States

University of Wisconsin
Madison, Wisconsin, United States

Medical College of Wisconsin
Milwaukee, Wisconsin, United States

Contacts

Leap Therapeutics, Inc.
617-714-0360
EarlyAccess@leaptx.com

Leap Therapeutics, Inc.
NCT Number
Keywords
DKK1
DKN-01
epithelial histology
Wnt pathway
endometrial
uterine
ovarian
carcinosarcoma
gastric cancer
gastroesophageal junction
MeSH Terms
Adenocarcinoma
Stomach Neoplasms
Endometrial Neoplasms
Esophageal Neoplasms
Uterine Neoplasms
Carcinosarcoma
Mixed Tumor, Mullerian