Symptoms and General Pathology

All Conditions

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Recurrence

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Uterine Neoplasms

Carcinosarcoma

Mixed Tumor, Mullerian

Carcinoma

Endometrial Neoplasms

Adenoma, Pleomorphic

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Uterine Diseases

Sarcoma

Neoplasms, Connective and Soft Tissue

Ovarian Cancer

Ovarian Epithelial Cancer

Malignant Mixed Mullerian Tumor

Soft Tissue Sarcoma

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

300mg DKN-01 monotherapy in recurrent EEC

300mg DKN-01 monotherapy in recurrent EOC

600mg DKN-01 monotherapy in carcinosarcoma

600mg DKN-01 +paclitaxel in carcinosarcoma

300mg DKN-01

600mg DKN-01

Cynthia Sirard, MD

Rebecca Arend, MD

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

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)

A Study of DKN-01 as a Monotherapy or in Combination With Paclitaxel in Patients With Recurrent Epithelial Endometrial or Epithelial Ovarian Cancer or Carcinosarcoma

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, Epithelial Ovarian Cancer, or Carcinosarcoma

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)

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)

Overall Survival (OS) is defined as the time from first dose of study drug until date of death due to any cause.

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) 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 participants analyzed only includes patients with a CR and is otherwise defined and analyzed similar to DoR.

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.

Leap Therapeutics, Inc.

Adverse events and serious adverse events reported are those that started or worsened after the first dose of study treatment and within 30 days after the last study treatment dose.

300mg DKN-01 monotherapy in recurrent EEC. DKN-01 administered by IV infusion.

DKN-01 Monotherapy in Recurrent EEC

300mg DKN-01+paclitaxel in recurrent EEC. DKN-01 administered by IV infusion.

DKN-01+Paclitaxel in Recurrent EEC

300mg DKN-01 monotherapy in recurrent EOC. DKN-01 administered by IV infusion.

DKN-01 Monotherapy in Recurrent EOC

300mg DKN-01+paclitaxel in recurrent EOC. DKN-01and paclitaxel administered by IV infusion.

DKN-01+Paclitaxel in Recurrent EOC

300mg DKN-01 monotherapy in carcinosarcoma. DKN-01 administered by IV infusion.

300mg DKN-01 Monotherapy in Carcinosarcoma

600mg DKN-01 monotherapy in carcinosarcoma. DKN-01 administered by IV infusion.

600mg DKN-01 Monotherapy in Carcinosarcoma

300mg DKN-01+paclitaxel in carcinosarcoma. DKN-01 and paclitaxel administered by IV infusion.

300mg DKN-01+Paclitaxel in Carcinosarcoma

600mg DKN-01+paclitaxel in carcinosarcoma. DKN-01 and paclitaxel administered by IV infusion.

600mg DKN-01+Paclitaxel in Carcinosarcoma

300mg DKN-01+paclitaxel in recurrent EEC. DKN-01 and paclitaxel administered by IV infusion.

300mg DKN-01+paclitaxel in recurrent EOC. DKN-01 and paclitaxel administered by IV infusion.

DKN-01 300mg Monotherapy in Carcinosarcoma

DKN-01 600mg Monotherapy in Carcinosarcoma

300mg DKN-01 +paclitaxel in carcinosarcoma. DKN-01 and paclitaxel administered by IV infusion.

DKN-01 300mg+Paclitaxel in Carcinosarcoma

600mg DKN-01 +paclitaxel in carcinosarcoma. DKN-01 and paclitaxel administered by IV infusion.

DKN-01 600mg+Paclitaxel in Carcinosarcoma

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Cynthia Sirard, MD, Chief Medical Officer

Complete Response

Partial Response

Stable Disease

Progressive Disease

DKN-01 + Paclitaxel in Recurrent EEC

DKN-01 + Paclitaxel in Recurrent EOC

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.

Number of Subjects With Objective Response Rate (ORR) in EEC or EOC Patients

Confirmed ORR

300mg DKN-01 + paclitaxel in carcinosarcoma. DKN-01 and paclitaxel administered by IV infusion.

DKN-01 300mg + Paclitaxel in Carcinosarcoma

600mg DKN-01 + paclitaxel in carcinosarcoma. DKN-01 and paclitaxel administered by IV infusion.

DKN-01 600mg + Paclitaxel in Carcinosarcoma

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.

Number of Subjects With Objective Response Rate (ORR) in Carcinosarcoma (MMMT) Patients

Number of Subjects With Objective Disease Control Rate (ODCR) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT).

Full Analysis Set (FAS), all subjects who received any amount of DKN-01.

Overall Survival (OS) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT).

600mg DKN-01 onotherapy in carcinosarcoma. DKN-01 administered by IV infusion.

Progression-free Survival (PFS) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT).

DKN-01 + Paclitaxel in Eecurrent EOC

300mg DKN-01 in carcinosarcoma. DKN-01 administered by IV infusion.

Number of participants analyzed only includes the responders in each group.

Duration of Response (DoR) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT).

300mg DKN-01 + paclitaxel in recurrent EEC. DKN-01 and paclitaxel administered by IV infusion.

300mg DKN-01 + paclitaxel in recurrent EOC. DKN-01 and paclitaxel administered by IV infusion.

Number of participants analyzed only includes patients who have responded with an objective disease response (CR).

Duration of Complete Response (DoCR) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT).

DKN-01 300mg + Paclitaxel in Carcinsarcoma

Number of participants analyzed only includes patients who had CR, PR, or SD.

Duration of Clinical Benefit (DoCB) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT).

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)

Dickkopf-1 (DKK1) Concentration in Serum and Plasma Relative to Safety and Efficacy Outcomes in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT).

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

Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0

Maximum Plasma Concentration (Cmax)

Time Taken to Reach the Maximum Plasma Concentration (Tmax)

Area Under the Curve (AUC)

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)

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

Concentration of DKN-01 Antibodies in Human Serum in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT)

DKN-01 600 mg + Paclitaxel in Carcinosarcoma

Overall Study

Digestive System Diseases

Carcinoma, Squamous Cell

Adenocarcinoma

Stomach Neoplasms

Esophageal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Stomach Diseases

Head and Neck Neoplasms

Esophageal Diseases

Stomach Cancer

Esophageal Cancer

DKN-01

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of DKN-01 as a Monotherapy or in Combination With Paclitaxel in Patients With Recurrent Epithelial Endometrial or Epithelial Ovarian Cancer or Carcinosarcoma	NCT03395080	Endometrial Can... Uterine Cancer Ovarian Cancer Carcinosarcoma	Paclitaxel 300mg DKN-01 600mg DKN-01	18 Years -	Leap Therapeutics, Inc.
Expanded Access Use of DKN-01 for the Treatment of Advanced Solid Tumors	NCT04681248	Esophageal Neop... Adenocarcinoma ... GastroEsophagea... Squamous Cell C... Gastric Adenoca... Endometrial Can... Uterine Cancer Ovarian Cancer Carcinosarcoma Gastric Cancer	DKN-01	18 Years -	Leap Therapeutics, Inc.
A Study of DKN-01 as a Monotherapy or in Combination With Paclitaxel in Patients With Recurrent Epithelial Endometrial or Epithelial Ovarian Cancer or Carcinosarcoma	NCT03395080	Endometrial Can... Uterine Cancer Ovarian Cancer Carcinosarcoma	Paclitaxel 300mg DKN-01 600mg DKN-01	18 Years -	Leap Therapeutics, Inc.

Spots Global Cancer Trial Database for epithelial histology