Carcinosarcoma, Endometrial Cancer, Ovarian Cancer, Uterine Cancer
Conditions
Keywords
epithelial histology, Wnt pathway, DKK1, endometrial, uterine, ovarian, carcinosarcoma
Brief summary
A Phase 2 Study Evaluating the Efficacy and Safety of DKN-01 as a Monotherapy or in Combination with Paclitaxel in Patients With Recurrent Epithelial Endometrial Cancer, Epithelial Ovarian Cancer, or Carcinosarcoma
Detailed description
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)
Interventions
DRUGPaclitaxel
Administered by IV infusion
DRUG300mg DKN-01
Administered by IV infusion
DRUG600mg DKN-01
Administered by IV infusion
Sponsors
Leap Therapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Diagnosis: 1. Epithelial Endometrial Cancer: histologically confirmed diagnosis (by either primary surgical specimen or biopsy for recurrence) of recurrent previously treated EEC. 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 platinum-based chemotherapy). 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 study drug. 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.
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Objective Response Rate (ORR) in EEC or EOC Patients | Baseline to study completion (approximately 6 months) | Best overall response of Complete Response (CR; disappearance of all target lesions, any pathological lymph nodes whether target or non-target must have reduction in short axis to \<10mm) or Partial Response (PR; at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters) as assessed by the Investigator per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1) |
| Number of Subjects With Objective Response Rate (ORR) in Carcinosarcoma (MMMT) Patients | Baseline to study completion (approximately 6 months) | Best overall response of Complete Response (CR; disappearance of all target lesions, any pathological lymph nodes whether target or non-target must have reduction in short axis to \<10mm) or Partial Response (PR; at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters) as assessed by the Investigator per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT). | Baseline to study completion (maximum 7.1 months) | Progression-free survival (PFS) is defined as time from first dose of study drug to first documentation of PD (per RECIST 1.1) or death due to any cause. |
| Duration of Response (DoR) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT). | Baseline to study completion (approximately 11 months) | Duration of Response (DoR) includes only patients that have responded with an objective disease response (PR or CR) and is defined as the time from the first tumor assessment that supports the patient's objective disease response to the time of PD or death due to any cause. |
| Number of Subjects With Objective Disease Control Rate (ODCR) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT). | Baseline to study completion (approximately 6 months) | Objective Disease Control Rate (ODCR) was defined as the percentage of subjects with a Best Overall Response of Complete Response (CR; disappearance of all target lesions, any pathological lymph nodes whether target or non-target must have reduction in short axis to \<10mm), Partial Response (PR; at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters), or Stable Disease (neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify as Progressive Disease) as assessed by the Investigator per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1) |
| Duration of Clinical Benefit (DoCB) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT). | Baseline to study completion (approximately 13.1 months) | Duration of Clinical Benefit (DoCB) includes patients with a Best Overall Response of CR, PR, or SD and is defined as the time from the first tumor assessment of CR, PR or SD to the time of PD or death due to any cause. |
| Duration of Complete Response (DoCR) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT). | Baseline to study completion (approximately 11 months) | Number of participants analyzed only includes patients with a CR and is otherwise defined and analyzed similar to DoR. |
| Overall Survival (OS) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT). | Baseline to study completion (maximum 17.6 months) | Overall Survival (OS) is defined as the time from first dose of study drug until date of death due to any cause. |
Other
| Measure | Time frame |
|---|---|
| Number of Subjects With Adverse Drug Reactions and Toxicities to Study Treatment Regimen in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT) as Evaluated by NCI CTCAE v5.0 | Baseline to study completion (approximately 6 months) |
| Number of Subjects With Response to Therapy in Patients With and Without Activating β-catenin Mutations and/or Wnt Signaling Genetic Alterations in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT) | Baseline to study completion (approximately 6 months) |
| Concentration of DKN-01 Antibodies in Human Serum in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT) | Baseline to study completion (approximately 6 months) |
| Dickkopf-1 (DKK1) Concentration in Serum and Plasma Relative to Safety and Efficacy Outcomes in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT). | Baseline to study completion (approximately 6 months) |
| Number of Subjects With Adverse Drug Reactions and Toxicities as Evaluated by NCI CTCAE v5.0 of DKN-01 600 mg +/- Paclitaxel in Patients With Recurrent Carcinosarcoma (MMMT) in Carcinosarcoma (MMMT) Patients | Baseline to study completion (approximately 6 months) |
| Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | Baseline to study completion (approximately 6 months) |
| Maximum Plasma Concentration (Cmax) | Baseline to study completion (approximately 6 months) |
| Time Taken to Reach the Maximum Plasma Concentration (Tmax) | Baseline to study completion (approximately 6 months) |
| Area Under the Curve (AUC) | Baseline to study completion (approximately 6 months) |
| Number of Subjects With Adverse Drug Reactions and Toxicities as Evaluated by NCI CTCAE v4.03 as DKN-01 as Monotherapy or in Combination With Paclitaxel in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT) | Baseline to study completion (approximately 6 months) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| DKN-01 Monotherapy in Recurrent EEC 300mg DKN-01 monotherapy in recurrent EEC. DKN-01 administered by IV infusion. | 29 |
| DKN-01+Paclitaxel in Recurrent EEC 300mg DKN-01+paclitaxel in recurrent EEC. DKN-01 and paclitaxel administered by IV infusion. | 24 |
| DKN-01 Monotherapy in Recurrent EOC 300mg DKN-01 monotherapy in recurrent EOC. DKN-01 administered by IV infusion. | 14 |
| DKN-01+Paclitaxel in Recurrent EOC 300mg DKN-01+paclitaxel in recurrent EOC. DKN-01 and paclitaxel administered by IV infusion. | 19 |
| DKN-01 300mg Monotherapy in Carcinosarcoma 300mg DKN-01 monotherapy in carcinosarcoma. DKN-01 administered by IV infusion. | 1 |
| DKN-01 600mg Monotherapy in Carcinosarcoma 600mg DKN-01 monotherapy in carcinosarcoma. DKN-01 administered by IV infusion. | 8 |
| DKN-01 300mg+Paclitaxel in Carcinosarcoma 300mg DKN-01 +paclitaxel in carcinosarcoma. DKN-01 and paclitaxel administered by IV infusion. | 4 |
| DKN-01 600mg+Paclitaxel in Carcinosarcoma 600mg DKN-01 +paclitaxel in carcinosarcoma. DKN-01 and paclitaxel administered by IV infusion. | 12 |
| Total | 111 |
Baseline characteristics
| Characteristic | Total | DKN-01+Paclitaxel in Recurrent EEC | DKN-01 Monotherapy in Recurrent EEC | DKN-01 Monotherapy in Recurrent EOC | DKN-01+Paclitaxel in Recurrent EOC | DKN-01 300mg Monotherapy in Carcinosarcoma | DKN-01 600mg Monotherapy in Carcinosarcoma | DKN-01 300mg+Paclitaxel in Carcinosarcoma | DKN-01 600mg+Paclitaxel in Carcinosarcoma |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 52 Participants | 12 Participants | 10 Participants | 9 Participants | 9 Participants | 0 Participants | 6 Participants | 2 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 59 Participants | 12 Participants | 19 Participants | 5 Participants | 10 Participants | 1 Participants | 2 Participants | 2 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 0 Participants | 4 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 102 Participants | 23 Participants | 25 Participants | 14 Participants | 18 Participants | 1 Participants | 7 Participants | 4 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 2 Participants | 0 Participants | 2 Participants | 3 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 97 Participants | 21 Participants | 27 Participants | 12 Participants | 16 Participants | 1 Participants | 7 Participants | 4 Participants | 9 Participants |
| Sex: Female, Male Female | 111 Participants | 24 Participants | 29 Participants | 14 Participants | 19 Participants | 1 Participants | 8 Participants | 4 Participants | 12 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 14 / 29 | 16 / 24 | 11 / 14 | 12 / 19 | 0 / 1 | 4 / 8 | 2 / 4 | 8 / 12 |
| other Total, other adverse events | 29 / 29 | 24 / 24 | 13 / 14 | 19 / 19 | 1 / 1 | 8 / 8 | 4 / 4 | 12 / 12 |
| serious Total, serious adverse events | 8 / 29 | 13 / 24 | 1 / 14 | 6 / 19 | 1 / 1 | 2 / 8 | 0 / 4 | 6 / 12 |
Outcome results
Primary
Number of Subjects With Objective Response Rate (ORR) in Carcinosarcoma (MMMT) Patients
Best overall response of Complete Response (CR; disappearance of all target lesions, any pathological lymph nodes whether target or non-target must have reduction in short axis to \<10mm) or Partial Response (PR; at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters) as assessed by the Investigator per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1)
Time frame: Baseline to study completion (approximately 6 months)
Population: Evaluable Analysis Set, all subjects who received any amount of DKN-01 and had at least 1 evaluated post-baseline RECIST assessment or were discontinued due to death.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DKN-01 Monotherapy in Recurrent EEC | Number of Subjects With Objective Response Rate (ORR) in Carcinosarcoma (MMMT) Patients | Complete Response | 0 participants |
| DKN-01 Monotherapy in Recurrent EEC | Number of Subjects With Objective Response Rate (ORR) in Carcinosarcoma (MMMT) Patients | Confirmed ORR | 0 participants |
| DKN-01 Monotherapy in Recurrent EEC | Number of Subjects With Objective Response Rate (ORR) in Carcinosarcoma (MMMT) Patients | Partial Response | 0 participants |
| DKN-01 Monotherapy in Recurrent EEC | Number of Subjects With Objective Response Rate (ORR) in Carcinosarcoma (MMMT) Patients | Progressive Disease | 0 participants |
| DKN-01 Monotherapy in Recurrent EEC | Number of Subjects With Objective Response Rate (ORR) in Carcinosarcoma (MMMT) Patients | Stable Disease | 1 participants |
| DKN-01 + Paclitaxel in Recurrent EEC | Number of Subjects With Objective Response Rate (ORR) in Carcinosarcoma (MMMT) Patients | Progressive Disease | 7 participants |
| DKN-01 + Paclitaxel in Recurrent EEC | Number of Subjects With Objective Response Rate (ORR) in Carcinosarcoma (MMMT) Patients | Confirmed ORR | 0 participants |
| DKN-01 + Paclitaxel in Recurrent EEC | Number of Subjects With Objective Response Rate (ORR) in Carcinosarcoma (MMMT) Patients | Complete Response | 0 participants |
| DKN-01 + Paclitaxel in Recurrent EEC | Number of Subjects With Objective Response Rate (ORR) in Carcinosarcoma (MMMT) Patients | Partial Response | 0 participants |
| DKN-01 + Paclitaxel in Recurrent EEC | Number of Subjects With Objective Response Rate (ORR) in Carcinosarcoma (MMMT) Patients | Stable Disease | 1 participants |
| DKN-01 Monotherapy in Recurrent EOC | Number of Subjects With Objective Response Rate (ORR) in Carcinosarcoma (MMMT) Patients | Complete Response | 0 participants |
| DKN-01 Monotherapy in Recurrent EOC | Number of Subjects With Objective Response Rate (ORR) in Carcinosarcoma (MMMT) Patients | Partial Response | 1 participants |
| DKN-01 Monotherapy in Recurrent EOC | Number of Subjects With Objective Response Rate (ORR) in Carcinosarcoma (MMMT) Patients | Stable Disease | 0 participants |
| DKN-01 Monotherapy in Recurrent EOC | Number of Subjects With Objective Response Rate (ORR) in Carcinosarcoma (MMMT) Patients | Confirmed ORR | 1 participants |
| DKN-01 Monotherapy in Recurrent EOC | Number of Subjects With Objective Response Rate (ORR) in Carcinosarcoma (MMMT) Patients | Progressive Disease | 3 participants |
| DKN-01 + Paclitaxel in Recurrent EOC | Number of Subjects With Objective Response Rate (ORR) in Carcinosarcoma (MMMT) Patients | Complete Response | 0 participants |
| DKN-01 + Paclitaxel in Recurrent EOC | Number of Subjects With Objective Response Rate (ORR) in Carcinosarcoma (MMMT) Patients | Stable Disease | 4 participants |
| DKN-01 + Paclitaxel in Recurrent EOC | Number of Subjects With Objective Response Rate (ORR) in Carcinosarcoma (MMMT) Patients | Partial Response | 1 participants |
| DKN-01 + Paclitaxel in Recurrent EOC | Number of Subjects With Objective Response Rate (ORR) in Carcinosarcoma (MMMT) Patients | Confirmed ORR | 1 participants |
| DKN-01 + Paclitaxel in Recurrent EOC | Number of Subjects With Objective Response Rate (ORR) in Carcinosarcoma (MMMT) Patients | Progressive Disease | 5 participants |
Primary
Number of Subjects With Objective Response Rate (ORR) in EEC or EOC Patients
Best overall response of Complete Response (CR; disappearance of all target lesions, any pathological lymph nodes whether target or non-target must have reduction in short axis to \<10mm) or Partial Response (PR; at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters) as assessed by the Investigator per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1)
Time frame: Baseline to study completion (approximately 6 months)
Population: Evaluable Analysis Set (EAS), all subjects who received any amount of DKN-01 and had at least 1 evaluated post-baseline RECIST assessment or were discontinued due to death.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DKN-01 Monotherapy in Recurrent EEC | Number of Subjects With Objective Response Rate (ORR) in EEC or EOC Patients | Stable Disease | 9 participants |
| DKN-01 Monotherapy in Recurrent EEC | Number of Subjects With Objective Response Rate (ORR) in EEC or EOC Patients | Complete Response | 1 participants |
| DKN-01 Monotherapy in Recurrent EEC | Number of Subjects With Objective Response Rate (ORR) in EEC or EOC Patients | Progressive Disease | 15 participants |
| DKN-01 Monotherapy in Recurrent EEC | Number of Subjects With Objective Response Rate (ORR) in EEC or EOC Patients | Partial Response | 1 participants |
| DKN-01 Monotherapy in Recurrent EEC | Number of Subjects With Objective Response Rate (ORR) in EEC or EOC Patients | ORR | 2 participants |
| DKN-01 + Paclitaxel in Recurrent EEC | Number of Subjects With Objective Response Rate (ORR) in EEC or EOC Patients | Partial Response | 0 participants |
| DKN-01 + Paclitaxel in Recurrent EEC | Number of Subjects With Objective Response Rate (ORR) in EEC or EOC Patients | Stable Disease | 12 participants |
| DKN-01 + Paclitaxel in Recurrent EEC | Number of Subjects With Objective Response Rate (ORR) in EEC or EOC Patients | Progressive Disease | 9 participants |
| DKN-01 + Paclitaxel in Recurrent EEC | Number of Subjects With Objective Response Rate (ORR) in EEC or EOC Patients | Complete Response | 0 participants |
| DKN-01 + Paclitaxel in Recurrent EEC | Number of Subjects With Objective Response Rate (ORR) in EEC or EOC Patients | ORR | 0 participants |
| DKN-01 Monotherapy in Recurrent EOC | Number of Subjects With Objective Response Rate (ORR) in EEC or EOC Patients | Partial Response | 0 participants |
| DKN-01 Monotherapy in Recurrent EOC | Number of Subjects With Objective Response Rate (ORR) in EEC or EOC Patients | ORR | 0 participants |
| DKN-01 Monotherapy in Recurrent EOC | Number of Subjects With Objective Response Rate (ORR) in EEC or EOC Patients | Complete Response | 0 participants |
| DKN-01 Monotherapy in Recurrent EOC | Number of Subjects With Objective Response Rate (ORR) in EEC or EOC Patients | Stable Disease | 6 participants |
| DKN-01 Monotherapy in Recurrent EOC | Number of Subjects With Objective Response Rate (ORR) in EEC or EOC Patients | Progressive Disease | 7 participants |
| DKN-01 + Paclitaxel in Recurrent EOC | Number of Subjects With Objective Response Rate (ORR) in EEC or EOC Patients | Stable Disease | 13 participants |
| DKN-01 + Paclitaxel in Recurrent EOC | Number of Subjects With Objective Response Rate (ORR) in EEC or EOC Patients | Complete Response | 0 participants |
| DKN-01 + Paclitaxel in Recurrent EOC | Number of Subjects With Objective Response Rate (ORR) in EEC or EOC Patients | ORR | 0 participants |
| DKN-01 + Paclitaxel in Recurrent EOC | Number of Subjects With Objective Response Rate (ORR) in EEC or EOC Patients | Partial Response | 0 participants |
| DKN-01 + Paclitaxel in Recurrent EOC | Number of Subjects With Objective Response Rate (ORR) in EEC or EOC Patients | Progressive Disease | 6 participants |
Secondary
Duration of Clinical Benefit (DoCB) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT).
Duration of Clinical Benefit (DoCB) includes patients with a Best Overall Response of CR, PR, or SD and is defined as the time from the first tumor assessment of CR, PR or SD to the time of PD or death due to any cause.
Time frame: Baseline to study completion (approximately 13.1 months)
Population: Number of participants analyzed only includes patients who had CR, PR, or SD.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DKN-01 Monotherapy in Recurrent EEC | Duration of Clinical Benefit (DoCB) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT). | 4.7 months |
| DKN-01 + Paclitaxel in Recurrent EEC | Duration of Clinical Benefit (DoCB) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT). | 3.8 months |
| DKN-01 Monotherapy in Recurrent EOC | Duration of Clinical Benefit (DoCB) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT). | 1.9 months |
| DKN-01 + Paclitaxel in Recurrent EOC | Duration of Clinical Benefit (DoCB) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT). | 3.9 months |
| DKN-01 300mg Monotherapy in Carcinosarcoma | Duration of Clinical Benefit (DoCB) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT). | NA months |
| DKN-01 600mg Monotherapy in Carcinosarcoma | Duration of Clinical Benefit (DoCB) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT). | 6.0 months |
| DKN-01 300mg + Paclitaxel in Carcinosarcoma | Duration of Clinical Benefit (DoCB) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT). | 3.7 months |
| DKN-01 600mg + Paclitaxel in Carcinosarcoma | Duration of Clinical Benefit (DoCB) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT). | 2.2 months |
Secondary
Duration of Complete Response (DoCR) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT).
Number of participants analyzed only includes patients with a CR and is otherwise defined and analyzed similar to DoR.
Time frame: Baseline to study completion (approximately 11 months)
Population: Number of participants analyzed only includes patients who have responded with an objective disease response (CR).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DKN-01 Monotherapy in Recurrent EEC | Duration of Complete Response (DoCR) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT). | NA months |
Secondary
Duration of Response (DoR) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT).
Duration of Response (DoR) includes only patients that have responded with an objective disease response (PR or CR) and is defined as the time from the first tumor assessment that supports the patient's objective disease response to the time of PD or death due to any cause.
Time frame: Baseline to study completion (approximately 11 months)
Population: Number of participants analyzed only includes the responders in each group.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DKN-01 Monotherapy in Recurrent EEC | Duration of Response (DoR) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT). | NA months |
| DKN-01 300mg + Paclitaxel in Carcinosarcoma | Duration of Response (DoR) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT). | 3.7 months |
| DKN-01 600mg + Paclitaxel in Carcinosarcoma | Duration of Response (DoR) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT). | NA months |
Secondary
Number of Subjects With Objective Disease Control Rate (ODCR) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT).
Objective Disease Control Rate (ODCR) was defined as the percentage of subjects with a Best Overall Response of Complete Response (CR; disappearance of all target lesions, any pathological lymph nodes whether target or non-target must have reduction in short axis to \<10mm), Partial Response (PR; at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters), or Stable Disease (neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify as Progressive Disease) as assessed by the Investigator per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1)
Time frame: Baseline to study completion (approximately 6 months)
Population: Evaluable Analysis Set (EAS), all subjects who received any amount of DKN-01 and had at least 1 evaluated post-baseline RECIST assessment or were discontinued due to death.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DKN-01 Monotherapy in Recurrent EEC | Number of Subjects With Objective Disease Control Rate (ODCR) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT). | 11 Participants |
| DKN-01 + Paclitaxel in Recurrent EEC | Number of Subjects With Objective Disease Control Rate (ODCR) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT). | 12 Participants |
| DKN-01 Monotherapy in Recurrent EOC | Number of Subjects With Objective Disease Control Rate (ODCR) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT). | 6 Participants |
| DKN-01 + Paclitaxel in Recurrent EOC | Number of Subjects With Objective Disease Control Rate (ODCR) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT). | 13 Participants |
| DKN-01 300mg Monotherapy in Carcinosarcoma | Number of Subjects With Objective Disease Control Rate (ODCR) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT). | 1 Participants |
| DKN-01 600mg Monotherapy in Carcinosarcoma | Number of Subjects With Objective Disease Control Rate (ODCR) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT). | 1 Participants |
| DKN-01 300mg + Paclitaxel in Carcinosarcoma | Number of Subjects With Objective Disease Control Rate (ODCR) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT). | 1 Participants |
| DKN-01 600mg + Paclitaxel in Carcinosarcoma | Number of Subjects With Objective Disease Control Rate (ODCR) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT). | 5 Participants |
Secondary
Overall Survival (OS) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT).
Overall Survival (OS) is defined as the time from first dose of study drug until date of death due to any cause.
Time frame: Baseline to study completion (maximum 17.6 months)
Population: Full Analysis Set (FAS), all subjects who received any amount of DKN-01.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DKN-01 Monotherapy in Recurrent EEC | Overall Survival (OS) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT). | 12.2 months |
| DKN-01 + Paclitaxel in Recurrent EEC | Overall Survival (OS) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT). | 10.1 months |
| DKN-01 Monotherapy in Recurrent EOC | Overall Survival (OS) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT). | 10.8 months |
| DKN-01 + Paclitaxel in Recurrent EOC | Overall Survival (OS) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT). | 11.9 months |
| DKN-01 300mg Monotherapy in Carcinosarcoma | Overall Survival (OS) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT). | NA months |
| DKN-01 600mg Monotherapy in Carcinosarcoma | Overall Survival (OS) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT). | 8.4 months |
| DKN-01 300mg + Paclitaxel in Carcinosarcoma | Overall Survival (OS) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT). | 7.3 months |
| DKN-01 600mg + Paclitaxel in Carcinosarcoma | Overall Survival (OS) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT). | 5.7 months |
Secondary
Progression-free Survival (PFS) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT).
Progression-free survival (PFS) is defined as time from first dose of study drug to first documentation of PD (per RECIST 1.1) or death due to any cause.
Time frame: Baseline to study completion (maximum 7.1 months)
Population: Full Analysis Set (FAS), all subjects who received any amount of DKN-01.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DKN-01 Monotherapy in Recurrent EEC | Progression-free Survival (PFS) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT). | 1.8 months |
| DKN-01 + Paclitaxel in Recurrent EEC | Progression-free Survival (PFS) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT). | 3.8 months |
| DKN-01 Monotherapy in Recurrent EOC | Progression-free Survival (PFS) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT). | 2.1 months |
| DKN-01 + Paclitaxel in Recurrent EOC | Progression-free Survival (PFS) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT). | 3.6 months |
| DKN-01 300mg Monotherapy in Carcinosarcoma | Progression-free Survival (PFS) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT). | 11.6 months |
| DKN-01 600mg Monotherapy in Carcinosarcoma | Progression-free Survival (PFS) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT). | 1.6 months |
| DKN-01 300mg + Paclitaxel in Carcinosarcoma | Progression-free Survival (PFS) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT). | 2.0 months |
| DKN-01 600mg + Paclitaxel in Carcinosarcoma | Progression-free Survival (PFS) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT). | 1.9 months |
Other Pre-specified
Area Under the Curve (AUC)
Time frame: Baseline to study completion (approximately 6 months)
Other Pre-specified
Concentration of DKN-01 Antibodies in Human Serum in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT)
Time frame: Baseline to study completion (approximately 6 months)
Other Pre-specified
Dickkopf-1 (DKK1) Concentration in Serum and Plasma Relative to Safety and Efficacy Outcomes in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT).
Time frame: Baseline to study completion (approximately 6 months)
Other Pre-specified
Maximum Plasma Concentration (Cmax)
Time frame: Baseline to study completion (approximately 6 months)
Other Pre-specified
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0
Time frame: Baseline to study completion (approximately 6 months)
Other Pre-specified
Number of Subjects With Adverse Drug Reactions and Toxicities as Evaluated by NCI CTCAE v4.03 as DKN-01 as Monotherapy or in Combination With Paclitaxel in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT)
Time frame: Baseline to study completion (approximately 6 months)
Other Pre-specified
Number of Subjects With Adverse Drug Reactions and Toxicities as Evaluated by NCI CTCAE v5.0 of DKN-01 600 mg +/- Paclitaxel in Patients With Recurrent Carcinosarcoma (MMMT) in Carcinosarcoma (MMMT) Patients
Time frame: Baseline to study completion (approximately 6 months)
Other Pre-specified
Number of Subjects With Adverse Drug Reactions and Toxicities to Study Treatment Regimen in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT) as Evaluated by NCI CTCAE v5.0
Time frame: Baseline to study completion (approximately 6 months)
Other Pre-specified
Number of Subjects With Response to Therapy in Patients With and Without Activating β-catenin Mutations and/or Wnt Signaling Genetic Alterations in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT)
Time frame: Baseline to study completion (approximately 6 months)
Other Pre-specified
Time Taken to Reach the Maximum Plasma Concentration (Tmax)
Time frame: Baseline to study completion (approximately 6 months)