This study employs a "basket" design to concurrently investigate DKN-01 as monotherapy and in
combination with paclitaxel in patients with recurrent epithelial endometrial cancer (EEC),
epithelial ovarian cancer (EOC), or carcinosarcoma (malignant mixed Mullerian tumor [MMMT].
Thus, 6 distinct patient groups are being independently investigated:
1. 300mg DKN-01 monotherapy in recurrent EEC (Group 1)
2. 300mg DKN-01+paclitaxel in recurrent EEC (Group 2)
3. 300mg DKN-01 monotherapy in recurrent EOC (Group 3)
4. 300mg DKN-01+paclitaxel in recurrent EOC (Group 4)
5. 600mg DKN-01 monotherapy in recurrent carcinosarcoma (MMMT) (Group 5)
6. 600mg DKN-01+paclitaxel in recurrent carcinosarcoma (MMMT) (Group 6)
1. Epithelial Endometrial Cancer: histologically confirmed diagnosis (by either
primary surgical specimen or biopsy for recurrence) of recurrent previously
2. Epithelial Ovarian Cancer: histologically confirmed diagnosis (by either primary
surgical specimen or biopsy for recurrence) of recurrent
platinum-resistant/refractory EOC, primary peritoneal, or fallopian tube cancer
(i.e., disease recurrence within 6 months of completion of or progression during
3. Carcinosarcoma/Malignant Mixed Mullerian Tumors: histologically confirmed
diagnosis (by either primary surgical specimen or biopsy for recurrence) of
recurrent uterine or ovarian carcinosarcoma (MMMT). Patients must have had only 1
prior chemotherapeutic regimen for management of carcinosarcoma that may have
been included chemotherapy (including in adjuvant setting), chemotherapy and
radiotherapy, and/or consolidation/maintenance therapy.
2. Refractory or intolerant to at least one prior standard therapy(ies) for metastatic or
locally advanced disease (see Inclusion Criterion #1c for Groups 5-6).
1. If prior therapy consisted of palliative chemoradiation therapy, it will be
considered one line of therapy.
2. Prior treatment with paclitaxel as part of definitive therapy regimen is
acceptable, provided the patient is not intolerant of paclitaxel.
3. Patients who are not eligible to receive paclitaxel will be allowed to receive
single agent DKN-01.
3. Tumor tissue for mandatory pre-treatment and on-treatment biopsies.
4. One or more tumors measurable on radiographic imaging as defined by RECIST 1.1.
5. Ambulatory and ≥18 years of age.
6. ECOG performance status (PS) of 0 or 1
a. ECOG PS of 2 may be eligible upon the review and approval of the Medical Monitor.
7. Estimated life expectancy of at least 3 months, in the judgment of the Investigator.
8. Disease-free of active second/secondary or prior malignancies for ≥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.
9. Acceptable liver, renal, hematologic and coagulation function
10. Females of child bearing potential and male partners of female patients must agree to
use adequate contraception during the study and for 6 months after their last dose of
11. Reliable and willing to make themselves available for the duration of the study and
are willing to follow study-specific procedures.
12. Provided written informed consent prior to any study-specific procedures.
1. Patients with the following pure histologies of endometrial or ovarian cancer are not
eligible for enrollment: germ cell, sex cord stroma, or sarcoma.
2. New York Heart Association Class III or IV cardiac disease, myocardial infarction
within the past 6 months, or unstable arrhythmia.
3. Fridericia-corrected QT interval (QTcF) > 470 msec (female) or history of congenital
long QT syndrome.
4. Active, uncontrolled bacterial, viral, or fungal infections, within 7 days of study
entry requiring systemic therapy.
5. Known to be human immunodeficiency virus (HIV) positive, have hepatitis B surface
antigen (HBSAg), or hepatitis C antibodies (HCAb), unless hepatitis C virus
ribonucleic acid (HCV RNA) undetected/negative.
6. History of major organ transplant (i.e., heart, lungs, liver, or kidney).
7. History of autologous/allogenic bone marrow transplant.
8. Serious nonmalignant disease
9. Pregnant or nursing.
10. 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.
11. Symptomatic central nervous system (CNS) malignancy or metastasis.
12. Known osteoblastic bony metastasis
13. Treatment with surgery or chemotherapy within 21 days prior to study entry (42 days
for nitrosoureas or mitomycin C)
14. Any hormonal therapy directed at the malignant tumor must be discontinued at least one
week prior to study entry.
15. 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
16. History of hypersensitivity reactions to paclitaxel or other drugs formulated in
Cremophor® EL (polyoxyethylated castor oil). Patients who exhibit these
hypersensitivities will be eligible to receive single agent DKN-01
17. Prior radiation therapy within 14 days prior to study entry
18. Currently receiving any other investigational agent or received an investigational
agent within last 30 days of study entry.
19. Previously treated with an anti-DKK1 therapy
20. Significant allergy to a pharmaceutical therapy that, in the opinion of the
Investigator, poses an increased risk to the patient
21. Active substance abuse