Phase 2 Study Evaluating the Efficacy of the Combination of DKN-01 (DKK1 Inhibitor, Leap Therapeutics) and Pembrolizumab in the Treatment of Advanced or Recurrent Endometrial Cancer

NCT05761951 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2022-0526NCI-2023-01855
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

To learn if the combination of DKN-01 and pembrolizumab can help to control advanced or recurrent endometrial cancer.

Conditions

Endometrial Cancer

Outcome Measures

Primary Outcomes (1)

• ). Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  through study completion; an average of 1 year.

Study Arms (2)

DKN-01

EXPERIMENTAL

Participants will receive DKN-01 by vein over about 30 minutes to 2 hours on Day 1 of each cycle, as well ason Day 15 of Cycle 1.

Drug: DKN-01; Drug: Pembrolizumab

Pembrolizumab

EXPERIMENTAL

Participants will receive pembrolizumab by vein over about 30 minutes on Day 1 of each cycle for up to 24 months.

Drug: DKN-01; Drug: Pembrolizumab

Interventions

DKN-01 DRUG

Given by IV (vein)

DKN-01; Pembrolizumab

Pembrolizumab DRUG

Given by IV (vein)

DKN-01; Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent and any locally-required authorization (e.g., HIPAA in the USA) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations.
• Female participants age ≥ 18 years at the time of signing informed consent.
• Must have histologically confirmed diagnosis of advanced or recurrent endometrioid endometrial cancer that is deemed non-curable with either surgery or radiation therapy. Mixed endometrioid patient will be allowed if the endometrioid component is greater than 50% of the tumor and does not include serous or carcinosarcoma. Non-endometrioid endometrial cancer must have a confirmed Wnt-activating mutation (CTNNB1, RNF-43, APC, AXIN1/2, RSPO2/3, and ZNRF3).
• Patients may have received up to 2 prior systemic therapies for recurrent disease. Note: Chemotherapy given in conjunction with radiation or as part of primary therapy does not count as prior systemic therapy for recurrence. Hormonal therapy does not count toward prior therapy.
• Must consent to allow for a pre-treatment tumor biopsy. Tumor material from biopsies done before the screening period are acceptable if the biopsy was performed within 3 months prior to the planned treatment start and no other systemic cancer therapy was administered in the interim. If a biopsy is performed as part of the study and the specimen is considered non-diagnostic or does not have enough tissue (occurs less than 10% of the time), archival tissue can be used to determine the study cohort and the patient can still participate in the trial.
• Must not have received/progressed on treatment with an anti-PD-1/L1 mAb administered either as monotherapy or in combination with other checkpoint inhibitors or other therapies.
• Patients must be off all other anti-tumor therapies (including immunologic agents) for at least four weeks prior to start of treatment. Patients on hormonal agents require a washout for 10 days
• Patients must be off all other anti-tumor therapies (including immunologic agents) for at least four weeks prior to study registration. Patients on hormonal agents require a washout for 10 days
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention.
• Women of childbearing potential (WoCBP) must be permanently or surgically sterilized (undergone a total hysterectomy, bilateral lubal tigation, or bilateral oophorectomy) or are postmenopausal for greater than 12 months. (If uncertain of amenorrhea for 12 months, a pregnancy test will be done to confirm pregnancy status.) If ovaries are present and were not previously menopausal at the time of hysterectomy, should have a serum estradiol \<10 pm/mL to confirm ovarian senescence.
• Adequate hematological organ function laboratory values are defined below:
• Absolute neutrophil count (ANC) ≥1500/µL
• Platelets ≥100 000/µL
• Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/La
• Adequate renal organ function laboratory values are defined below:

You may not qualify if:

• Have uterine sarcomas, carcinosarcomas, serous tumors (any component) or pure clear cell carcinomas without documentation of a Wnt-activating mutation (see Figure 2 for definition)
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
• Previously treated with an anti-DKK1 therapy.
• Has deficient mismatch repair (dMMR) or microsatellite instability (MSI-H) are excluded.
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to enrollment.
• Patient has not recovered from all toxicities related to prior anticancer therapies to NCI-CTCAEv5.0 Grade \<1 (Exception to this criterion: any grade of alopecia is eligible for the study).
• Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
• Major surgical procedures, open biopsy or significant traumatic injury within 4 weeks prior to treatment start (minor procedures within 1 week)
• Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. (Note: Administration of killed vaccines is allowed.)
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are eligible.
• Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging. Note: repeat imaging should be performed during study screening. Participants must be clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Note: Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Leap Therapeutics, Inc.: collaborator
• Merck Sharp & Dohme LLC: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Endometrial Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• Pamela Soliman, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2023
• First Posted: March 9, 2023
• Study Start: August 29, 2023
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): January 31, 2029
• Last Updated: February 11, 2026

Record last verified: 2026-02

Locations

US (1)