DKN-01 + Pembrolizumab for Endometrial Cancer

Overseen By Pamela Soliman, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Anti-PD-1, Anti-PD-L1

Disqualifiers: Uterine sarcomas, Autoimmune disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 24 months

60 Participants Needed

Trial Summary

What is the purpose of this trial?

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

Do I need to stop my current medications to join the trial?

Yes, you will need to stop taking all other anti-tumor therapies at least four weeks before starting the trial treatment. If you are on hormonal agents, you will need a 10-day break from them before starting the trial.

What data supports the effectiveness of the drug pembrolizumab for endometrial cancer?

Research shows that pembrolizumab, a drug that helps the immune system fight cancer, has been effective in treating advanced endometrial cancer with specific genetic features (MSI-H/dMMR) after other treatments have failed. It has shown durable antitumor activity and improved quality of life for patients in clinical studies. ^{1 2 3 4 5}

Is the combination of DKN-01 and Pembrolizumab safe for humans?

Pembrolizumab, also known as Keytruda, has been used safely in various cancers, including endometrial cancer and non-small-cell lung cancer, showing a good safety profile in clinical trials. However, specific safety data for the combination of DKN-01 and Pembrolizumab is not provided in the available research. ^{1 2 3 6 7}

What makes the drug DKN-01 + Pembrolizumab unique for treating endometrial cancer?

This drug combination is unique because it combines DKN-01, which targets a specific protein involved in cancer growth, with Pembrolizumab, an immune therapy that helps the body's immune system attack cancer cells. Pembrolizumab has shown effectiveness in treating advanced endometrial cancer with specific genetic features (MSI-H/dMMR), offering a new option for patients who have not responded to other treatments. ^{1 2 3 4 5}

Research Team

Pamela T. Soliman

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for women over 18 with advanced or recurrent endometrioid endometrial cancer that can't be cured by surgery or radiation. Participants may have had up to two prior treatments but not with anti-PD-1/L1 mAbs. They must have measurable disease, be in fair health (ECOG 0-2), and not pregnant or breastfeeding. Exclusions include certain other cancers, recent therapies, vaccines, surgeries, active infections, severe hypersensitivities, autoimmune diseases requiring treatment within the past two years, CNS metastases, and significant heart or gastrointestinal conditions.

Inclusion Criteria

I have not been treated with or worsened after anti-PD-1/L1 therapy.

Women of childbearing potential (WoCBP) must be permanently or surgically sterilized 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: ANC ≥1500/µL, Platelets ≥100 000/µL, Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/La

Exclusion Criteria

I have an autoimmune disease treated with medication in the last 2 years.

Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator

I have not received a live vaccine in the last 30 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive DKN-01 and pembrolizumab by vein. DKN-01 is administered on Day 1 and Day 15 of Cycle 1, and pembrolizumab is administered on Day 1 of each cycle for up to 24 months.

24 months

Day 1 and Day 15 of Cycle 1, then Day 1 of each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• DKN-01
• Pembrolizumab

Trial Overview The study tests if DKN-01 (a DKK1 inhibitor) combined with pembrolizumab controls advanced/recurrent endometrial cancer better than current options. It's a Phase 2 trial where participants receive both drugs to see how effective this combination is against their cancer.

Participant Groups

Group I: Pembrolizumab Experimental Treatment 2 Interventions

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

Group II: DKN-01 Experimental Treatment 2 Interventions

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.

DKN-01 is already approved in United States for the following indications:

Approved in United States as DKN-01 for:

• None approved; Orphan Drug Designation for gastric and gastroesophageal junction cancer

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Leap Therapeutics, Inc.

Industry Sponsor

Trials

16

Recruited

1,100+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In the KEYNOTE-158 study, pembrolizumab showed a clinically meaningful objective response rate in patients with advanced MSI-H/dMMR endometrial cancer, with 84 out of 90 patients completing health-related quality of life (HRQoL) assessments.

Patients receiving pembrolizumab experienced significant improvements in their quality of life, with mean scores on the QLQ-C30 and EQ-5D-3L questionnaires increasing notably, especially among those who achieved a complete or partial response to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related quality of life with pembrolizumab monotherapy in patients with previously treated advanced microsatellite instability high/mismatch repair deficient endometrial cancer in the KEYNOTE-158 study. O'Malley, DM., Bariani, GM., Cassier, PA., et al.[2022]

Pembrolizumab, an immune checkpoint inhibitor, has been approved for treating relapsed MSI-H endometrial cancer after chemotherapy, showing promise in restoring anti-tumor immunity by blocking PD-1 interactions.

Despite encouraging response rates in MSI-H patients, over 50% do not respond to pembrolizumab, highlighting the need for better understanding of MSI status and identifying specific patient populations that may benefit from treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab as a single agent for patients with MSI-H advanced endometrial carcinoma. Turinetto, M., Lombardo, V., Pisano, C., et al.[2022]

Pembrolizumab (Keytruda) is approved for treating advanced endometrial carcinoma that is microsatellite instability-high or mismatch repair deficient, specifically for patients whose disease has progressed after previous treatments.

This approval is significant for patients who are not candidates for curative surgery or radiation, providing a new therapeutic option for a challenging stage of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Approved Use for Keytruda. Aschenbrenner, DS.[2022]

In the KEYNOTE-158 study, pembrolizumab showed a 48% objective response rate in patients with advanced MSI-H/dMMR endometrial cancer, indicating significant antitumor activity.

The treatment was associated with manageable safety, with 76% of patients experiencing treatment-related adverse events, but no fatal events reported, highlighting its potential as a viable option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in Patients With Microsatellite Instability-High Advanced Endometrial Cancer: Results From the KEYNOTE-158 Study. O'Malley, DM., Bariani, GM., Cassier, PA., et al.[2023]

Pembrolizumab, a monoclonal antibody targeting PD-1, showed significant efficacy in treating a 79-year-old patient with advanced squamous cell lung cancer, leading to a complete response after just 3 cycles of treatment.

However, the patient developed acute myelomonocytic leukemia after starting pembrolizumab, highlighting a potential safety concern that warrants further investigation into the drug's effects on blood cell production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. Kim, HB., Park, SG., Hong, R., et al.[2020]

The TROPION-Lung08 phase III study is investigating the combination of datopotamab deruxtecan (Dato-DXd) and pembrolizumab as a first-line treatment for patients with advanced non-small-cell lung cancer (NSCLC) who have high PD-L1 expression and no actionable genomic alterations, aiming to improve long-term disease control compared to pembrolizumab alone.

Primary endpoints of the study include progression-free survival and overall survival, with secondary endpoints assessing response rates and safety, indicating a comprehensive evaluation of the new treatment's efficacy and safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TROPION-Lung08: phase III study of datopotamab deruxtecan plus pembrolizumab as first-line therapy for advanced NSCLC. Levy, BP., Felip, E., Reck, M., et al.[2023]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

References

1. United States pubmed.ncbi.nlm.nih.gov

Health-related quality of life with pembrolizumab monotherapy in patients with previously treated advanced microsatellite instability high/mismatch repair deficient endometrial cancer in the KEYNOTE-158 study. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab as a single agent for patients with MSI-H advanced endometrial carcinoma. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

New Approved Use for Keytruda. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Pembrolizumab in Patients With Microsatellite Instability-High Advanced Endometrial Cancer: Results From the KEYNOTE-158 Study. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. [2020]

6. England pubmed.ncbi.nlm.nih.gov

TROPION-Lung08: phase III study of datopotamab deruxtecan plus pembrolizumab as first-line therapy for advanced NSCLC. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]