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

25 Participants Needed

Trial Summary

What is the purpose of this trial?

Primary Objectives: To assess the antitumor activity (proportion of objective response by RECIST 1.1 criteria) of pembrolizumab with objective tumor response in patients with persistent, recurrent or metastatic endometrial cancer harboring an ultra-mutated or hyper-mutated (MMR gene-defective) phenotype identified by next generation sequencing (NGS) and comprehensive genomic profiling (CGP). To determine the nature and degree of toxicity of pembrolizumab as assessed by CTCAE in patients with persistent, recurrent or metastatic endometrial carcinoma. Secondary Objective(s): To estimate the duration of progression-free survival (PFS) and overall survival (OS).

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.

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

Pembrolizumab has shown effectiveness in treating advanced endometrial cancer that is microsatellite instability-high or mismatch repair deficient, especially in patients who have already tried other treatments. Studies like KEYNOTE-158 have demonstrated that pembrolizumab can lead to meaningful responses and improve quality of life in these patients. ^{1 2 3 4 5}

Is Pembrolizumab (Keytruda) generally safe for humans?

Pembrolizumab (Keytruda) is generally considered less toxic than traditional chemotherapy, but it can cause serious side effects. Some patients have experienced pneumonitis (lung inflammation) and type 1 diabetes (a condition where the body can't produce insulin), though these are rare. It's important to discuss potential risks with your doctor. ^{3 5 6 7 8}

What makes the drug pembrolizumab unique for treating endometrial cancer?

Pembrolizumab is unique for treating endometrial cancer because it is specifically approved for advanced cases that are microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), targeting the PD-1 pathway to help the immune system fight cancer cells. This makes it a novel option for patients who have progressed after other treatments and are not candidates for surgery or radiation. ^{1 2 3 4 5}

Research Team

Alessandro Santin

Principal Investigator

Yale University

Eligibility Criteria

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 am 18 years old or older.

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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, 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]

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 (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]

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]

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]

References

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

Obesity is associated with improved progression-free survival in Microsatellite-Instability-High endometrial cancer treated with pembrolizumab. [2023]

2. 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]

3. England pubmed.ncbi.nlm.nih.gov

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

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

New Approved Use for Keytruda. [2022]

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

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

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

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]

8. Korea (South) pubmed.ncbi.nlm.nih.gov

Real-World Experience with Pembrolizumab Treatment in Patients with Heavily Treated Recurrent Gynecologic Malignancies. [2023]