Pembrolizumab for Endometrial Cancer

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Yale University

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Autoimmune disease, Active infection, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 4 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of pembrolizumab in treating certain types of endometrial cancer, particularly in cases that have recurred or spread after treatment. Pembrolizumab helps the immune system target and destroy cancer cells. Researchers aim to assess its effectiveness and understand potential side effects. Individuals with endometrial cancer that hasn't responded to previous treatments and whose tumors have specific genetic changes might be suitable for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that you stop any prior hormonal therapy at least one week before starting the study and any other therapy, including chemotherapy and immunotherapy, at least three weeks before. If you are on investigational agents, they must be stopped at least 30 days before the study begins.

Is there any evidence suggesting that pembrolizumab is likely to be safe for humans?

Research has shown that pembrolizumab has been studied as a treatment for patients with advanced endometrial cancer. In studies involving patients with certain gene mutations, pembrolizumab was generally well-tolerated. These mutations, known as mismatch repair deficiencies, cause cancer cells to struggle with fixing DNA errors.

Safety data from various studies indicate that pembrolizumab is manageable for most patients. While side effects have been reported, many are not severe. Common side effects include tiredness, itching, rash, and diarrhea. More serious side effects can occur but are less common.

In another study, pembrolizumab was used with another drug, and no new safety issues emerged. This suggests that the safety of pembrolizumab aligns with previous findings.

Overall, pembrolizumab has demonstrated a safety profile consistent with earlier research. It is considered safe enough for testing in clinical trials for endometrial cancer, though monitoring for side effects remains important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for endometrial cancer?

Pembrolizumab is unique because it harnesses the power of the immune system to target endometrial cancer cells. Unlike standard chemotherapy treatments that attack cancer cells directly and often harm healthy cells, pembrolizumab is an immunotherapy that blocks the PD-1 pathway, helping the immune system recognize and destroy cancer cells more effectively. Researchers are excited about pembrolizumab because it offers a targeted approach with potentially fewer side effects, and it could provide a new option for patients whose cancer is resistant to traditional therapies.

What evidence suggests that pembrolizumab might be an effective treatment for endometrial cancer?

Research has shown that pembrolizumab, which participants in this trial will receive, can help treat certain types of advanced endometrial cancer. One study found that 46% of patients responded positively to pembrolizumab, with their tumors shrinking. Another study discovered that the drug delayed cancer progression by about 4.4 months compared to a placebo. These findings offer hope for patients with endometrial cancer that has a specific gene defect (MMR gene-defective), suggesting pembrolizumab might help control the disease. ^{5 6 7 8 9}

Who Is on the Research Team?

Alessandro Santin

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for adults with endometrial cancer that has returned or spread after chemotherapy. Participants must have a certain type of genetic change in their tumors, be in good physical condition (ECOG 0-1), and have recovered from previous treatments. Women who can bear children must agree to use contraception and not be pregnant.

Inclusion Criteria

My tumor is highly mutated according to specific genetic tests.

I have recovered from recent cancer treatments, but I may still have some nerve pain or damage.

I've had chemotherapy with radiation to enhance its effect.

Exclusion Criteria

I have previously been treated with specific immunotherapy drugs.

You have not used any experimental drugs or devices within the last four weeks before starting the trial.

You are pregnant or breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab 200 mg every 3 weeks via IV infusion

4 years

1 visit every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 years

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab

Trial Overview

The trial tests Pembrolizumab's effectiveness on patients with ultramutated or hypermutated endometrial cancer by measuring tumor response rates and monitoring the drug's safety profile. It also aims to estimate how long patients live without disease progression and overall survival time.

How Is the Trial Designed?

Group I: Pembrolizumab Experimental Treatment 1 Intervention

Pembrolizumab 200 mg, Q3W, IV Infusion, Day 1 of each 3 week cycle

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

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

Published Research Related to This Trial

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 a study of 44 women with advanced or recurrent MMRd/MSI-H endometrial adenocarcinomas treated with pembrolizumab, obesity (BMI≥30) was linked to a higher disease control rate (85.2%) compared to those with a BMI<30 (59.8%).

Patients with obesity also experienced significantly longer progression-free survival (PFS) while overall survival (OS) rates remained similar regardless of BMI, suggesting that body weight may influence treatment outcomes with pembrolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obesity is associated with improved progression-free survival in Microsatellite-Instability-High endometrial cancer treated with pembrolizumab. Bernard, L., How, JA., Patel, S., et al.[2023]

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, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[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 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]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Citations

1.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa2302312

Pembrolizumab plus Chemotherapy in Advanced ...

In the pMMR cohort, median progression-free survival was 13.1 months with pembrolizumab and 8.7 months with placebo (hazard ratio, 0.54; 95% CI, 0.41 to 0.71; P ...

2.

keytruda.com

keytruda.com/advanced-endometrial-cancer/clinical-trial-results-after-chemotherapy/

results from a clinical trial of keytruda after chemotherapy

KEYTRUDA may help shrink tumors in adults with certain types of advanced endometrial cancer · 46% of 90 adults responded to therapy and saw their tumors either ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8527559/

Pembrolizumab in endometrial cancer: Where we stand now

Indeed, 5-year survival ranges from 91% for FIGO IA disease to as low as 47% for FIGO IIIC and 17% for FIGO IV disease. Chemotherapy with carboplatin plus ...

4.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/41009360/

The Efficacy of Pembrolizumab Immunotherapy in ...

The results suggest a potential long-term treatment effect, although the limitations of the RCT and the variability in the therapeutic regimens ...

5.

cancer.gov

cancer.gov/news-events/cancer-currents-blog/2024/endometrial-cancer-durvalumab-pembrolizumab-chemotherapy

Imfinzi, Keytruda Approved for Some Endometrial Cancers

The most recent data from the clinical trial that led to the dostarlimab approval, called RUBY, showed that it improved overall survival for ...

6.

ncbi.nlm.nih.gov

ncbi.nlm.nih.gov/books/NBK596607/

Clinical Review - Pembrolizumab (Keytruda) - NCBI Bookshelf

The ITC included data from 79 patients with MSI-H advanced endometrial cancer who received pembrolizumab and 65 patients with dMMR advanced endometrial cancer ...

7.

merck.com

merck.com/news/keytruda-pembrolizumab-plus-lenvima-lenvatinib-demonstrates-durable-5-year-survival-benefit-versus-chemotherapy-for-patients-with-advanced-endometrial-carcinoma-following-one-prior-pla/

KEYTRUDA® (pembrolizumab) Plus LENVIMA® ...

At five years, KEYTRUDA plus LENVIMA showed a 16.7% overall survival (OS) rate for these patients with mismatch repair proficient (pMMR) advanced ...

8.

eisai.com

eisai.com/news/2025/news202573.html

LENVIMA® (lenvatinib) Plus KEYTRUDA® ...

In the five-year analysis, there were no new safety signals and the safety profile of LENVIMA plus KEYTRUDA was consistent with previously ...

9.

keytrudahcp.com

keytrudahcp.com/safety/adverse-reactions/advanced-or-recurrent-endometrial-carcinoma/

KEYNOTE-868: Selected Safety Profile & Adverse Reactions

Learn about adverse reactions to KEYTRUDA® (pembrolizumab) in patients with advanced or recurrent endometrial carcinoma. See selected safety profile in ...