An Expanded Access Protocol for use of DKN-01 for the treatment of advanced solid tumors.
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.
Drug: DKN-01
Administered by IV infusion
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).
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
Leap Therapeutics, Inc.
617-714-0360
EarlyAccess@leaptx.com