Pembrolizumab + Chemotherapy/Radiotherapy for Endometrial Cancer

Not currently recruiting at 298 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme Corp.

Must not be taking: Immunosuppressants, Steroids, PD-1 inhibitors

Disqualifiers: Recurrent cancer, Autoimmune disease, HIV, others

Stay on Your Current Meds You can continue your current medications while participating

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: 12

Duration: 36 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding pembrolizumab, an immunotherapy drug, to the usual chemotherapy and possibly radiotherapy can help people with endometrial cancer remain disease-free longer and improve survival rates. Participants will receive either pembrolizumab with chemotherapy or a placebo with chemotherapy, and some might also receive radiation treatment. This study suits individuals who have had surgery for endometrial cancer and are at high risk of recurrence. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on chronic systemic steroid therapy or any form of immunosuppressive therapy, you may need to stop or adjust it before starting the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that pembrolizumab, when combined with chemotherapy, is generally well-tolerated. In previous studies, patients receiving this combination had a 70% lower risk of disease progression compared to those who did not. This suggests the treatment can be effective with manageable side effects.

However, like any medication, pembrolizumab can cause side effects. Some patients experienced tiredness, nausea, and skin rash, but these were mostly mild. Serious side effects occurred less frequently. Pembrolizumab is already FDA-approved for other uses, indicating it has undergone safety testing in people.

In this trial, pembrolizumab is tested with standard chemotherapy. This combination has been used in other studies and has consistently shown a strong safety record. Participants will be closely monitored to manage any side effects. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for endometrial cancer?

Researchers are excited about pembrolizumab for endometrial cancer because it leverages a unique mechanism of action, unlike traditional chemotherapy. Pembrolizumab is an immunotherapy drug that works by blocking the PD-1 pathway, which can help the immune system recognize and attack cancer cells more effectively. Unlike the standard chemotherapy options, such as carboplatin and paclitaxel, which directly target and kill rapidly dividing cells, pembrolizumab empowers the body's own defenses to fight the cancer. This innovative approach has the potential to improve outcomes and offer a new line of defense against endometrial cancer.

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

Research has shown that adding pembrolizumab to chemotherapy can significantly reduce the risk of endometrial cancer progression. In this trial, participants in the pembrolizumab plus chemotherapy arm may experience similar benefits. Previous studies have shown that patients receiving both pembrolizumab and chemotherapy had a 70% lower chance of cancer progression compared to those who did not receive pembrolizumab. Specifically, one study found that 46% of adults with advanced endometrial cancer experienced tumor shrinkage with this combination treatment. Pembrolizumab has also demonstrated strong and lasting effects in fighting tumors, with generally manageable side effects. Overall, these findings suggest that pembrolizumab can be a powerful addition to chemotherapy for treating endometrial cancer. ^{1 6 7 8 9}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

This trial is for individuals with newly diagnosed endometrial cancer who've had surgery with curative intent and are at high risk of recurrence. They must be disease-free post-surgery, have not received prior radiation or systemic therapy, and have good performance status (ECOG 0 or 1). Participants need adequate organ function and cannot have certain conditions like active infections, known HIV/Hepatitis B/C infection, autoimmune diseases requiring recent treatment, or a history of severe reactions to the study drugs.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

I haven't had any treatments, including radiation or drugs, for my endometrial cancer.

I have provided a tissue sample from my current diagnosis for testing.

Exclusion Criteria

Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention

Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study

I have a type of uterine sarcoma, but not adenosarcoma.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab or placebo in combination with adjuvant chemotherapy, with optional radiotherapy

36 weeks

12 visits (in-person)

Radiotherapy (optional)

Participants may receive radiotherapy starting within 6 weeks of completion of chemotherapy

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 54 months

What Are the Treatments Tested in This Trial?

Interventions

• Brachytherapy
• Cisplatin
• Docetaxel
• External Beam Radiotherapy (EBRT)
• Paclitaxel
• Pembrolizumab

Trial Overview The study tests pembrolizumab combined with adjuvant chemotherapy versus placebo plus chemotherapy in patients who may also receive radiotherapy. The goal is to see if pembrolizumab improves disease-free survival (DFS) and overall survival (OS) compared to the placebo when both are added to standard chemotherapy after surgery.

How Is the Trial Designed?

Group I: Pembrolizumab + Chemotherapy Experimental Treatment 8 Interventions

Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for 6 cycles followed by pembrolizumab 400 mg IV on Day 1 of each 6-week cycle (Q6W) for an additional 6 cycles. During the Q3W dosing period of pembrolizumab, participants receive concurrent standard of care (SoC) chemotherapy for 4 or 6 cycles. Participants optionally receive radiotherapy starting within 6 weeks of completion of SoC chemotherapy. The SoC chemotherapy regimen includes carboplatin AUC 5 or 6 IV Q3W plus paclitaxel 175 mg/m\^2 IV Q3W. In the event of severe hypersensitivity to, or an AE requiring discontinuation of, carboplatin or paclitaxel, cisplatin or docetaxel may be substituted after investigator consults with sponsor. The SoC radiotherapy regimen may include, at the discretion of the investigator, external beam radiotherapy (EBRT) ≥4500 cGY with variable dose frequency, with or without cisplatin 50 mg/m\^2 IV on days 1 and 29 of EBRT, and/or brachytherapy radiation.

Group II: Placebo + Chemotherapy Placebo Group 8 Interventions

Participants receive placebo to pembrolizumab intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for 6 cycles followed by placebo IV on Day 1 of each 6-week cycle (Q6W) for an additional 6 cycles. During the Q3W dosing period of placebo, participants receive concurrent standard of care (SoC) chemotherapy for 4 or 6 cycles. Participants optionally receive radiotherapy starting within 6 weeks of completion of SoC chemotherapy. The SoC chemotherapy regimen includes carboplatin AUC 5 or 6 IV Q3W plus paclitaxel 175 mg/m\^2 IV Q3W. In the event of severe hypersensitivity to, or an AE requiring discontinuation of, carboplatin or paclitaxel, cisplatin or docetaxel may be substituted after investigator consults with sponsor. The SoC radiotherapy regimen may include, at the discretion of the investigator, external beam radiotherapy (EBRT) ≥4500 cGY with variable dose frequency, with or without cisplatin 50 mg/m\^2 IV on days 1 and 29 of EBRT, and/or brachytherapy radiation.

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?

Merck Sharp & Dohme Corp.

Lead Sponsor

Trials

2,287

Recruited

4,582,000+

Chirfi Guindo

Merck Sharp & Dohme Corp.

Chief Medical Officer

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

Robert M. Davis

Merck Sharp & Dohme Corp.

Chief Executive Officer since 2021

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

Merck Sharp & Dohme LLC

Lead 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

European Network for Gynaecological Oncological Trial Groups

Collaborator

Trials

4

Recruited

2,900+

Gynecologic Oncology Group

Collaborator

Trials

251

Recruited

65,400+

Published Research Related to This Trial

A case of advanced endometrial clear cell carcinoma (CCC), which typically has a poor prognosis and is resistant to standard chemotherapy, showed a successful treatment response using a combination of pembrolizumab (an immunotherapy), localized radiotherapy, and a few cycles of chemotherapy.

The patient experienced an extremely durable response, maintaining benefits even 3 years after stopping immunotherapy, highlighting the potential effectiveness of this treatment strategy for difficult-to-treat CCC cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case report: Durable response after pembrolizumab in combination with radiation - induced abscopal effect in platinum - refractory metastatic endometrial clear cell carcinoma. Kao, CH., Liu, CT., Lin, H., et al.[2023]

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 (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 phase 3 trial involving 816 patients with advanced or recurrent endometrial cancer, the addition of pembrolizumab to standard chemotherapy (paclitaxel plus carboplatin) significantly improved progression-free survival, especially in patients with mismatch repair-deficient (dMMR) tumors, showing a 70% reduction in the risk of progression or death.

For patients with mismatch repair-proficient (pMMR) tumors, pembrolizumab also enhanced progression-free survival compared to placebo, indicating its efficacy across different tumor types, while the safety profile was consistent with known effects of pembrolizumab and chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus Chemotherapy in Advanced Endometrial Cancer. Eskander, RN., Sill, MW., Beffa, L., et al.[2023]

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]

In a study of 48 patients with recurrent endometrial cancer treated with pembrolizumab and lenvatinib, the best objective response rate was 23.8%, indicating a lower effectiveness compared to clinical trial results.

The treatment was associated with notable side effects, with 56.2% of patients requiring a dose reduction of lenvatinib and 16.7% discontinuing treatment due to adverse events, highlighting the importance of monitoring for safety in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience of pembrolizumab and lenvatinib in recurrent endometrial cancer: A multicenter study in Korea. Kim, J., Noh, JJ., Lee, TK., et al.[2022]

In a phase II study involving 46 patients with advanced endometrial cancer, the combination of pembrolizumab with carboplatin and paclitaxel resulted in a high objective response rate (ORR) of 74.4%, significantly exceeding the historical control rate of 50%.

The treatment was generally well-tolerated, with common mild side effects like anemia and fatigue, while immune profiling indicated that responders had enriched CD8+ and CD4+ T cell populations, suggesting a potential mechanism of action related to immune response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and Biological Activity of Chemoimmunotherapy in Advanced Endometrial Adenocarcinoma: A Phase II Trial of the Big Ten Cancer Research Consortium. Barber, EL., Chen, S., Pineda, MJ., et al.[2023]

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, 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 this phase 3 trial, we found that the addition of pembrolizumab to standard chemotherapy, followed by pembrolizumab maintenance, resulted in a 70% lower risk ...

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. keytrudahcp.com keytrudahcp.com/efficacy/advanced-or-recurrent-endometrial-carcinoma/

KEYNOTE-868 - Clinical Trial Results & Study Design - Keytruda Surgical cancellation on the KEYTRUDA arm was due to disease progression in 4%, patient decision in 3%, adverse reactions in 1.4%, physician's decision in 1.1%, ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34990208/

Results From the KEYNOTE-158 Study - PubMed - NIH Conclusion: Pembrolizumab demonstrated robust and durable antitumor activity and encouraging survival outcomes with manageable toxicity in ...

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

Clinical Review - Pembrolizumab (Keytruda) - NCBI Bookshelf The objective of study KN-158 was to assess the efficacy and safety of pembrolizumab monotherapy for the treatment of adult patients with unresectable or ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02630823

MK-3475 Immunotherapy in Endometrial Carcinoma For patients whose pathology confirms high-risk features and advanced stage, MK-3475 will be given every 3 weeks starting 4 -6 weeks after completion of ...

8. keytruda.com keytruda.com/advanced-endometrial-cancer/clinical-trial-results/

Clinical Trial Results - Advanced Endometrial Cancer Review the results from clinical trials with KEYTRUDA® (pembrolizumab) in adults with certain types of advanced endometrial cancer. View results here.

9. 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 ...