Pembrolizumab + Radiation for Endometrial Cancer

Recruiting at 322 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

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

Disqualifiers: Autoimmune disease, Pneumonitis, Liver disease, others

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

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

Compensation: Varies

Number of Visits: 9

168 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This phase III trial compares whether the addition of pembrolizumab to radiation therapy is more effective than radiation therapy alone in reducing the risk of cancer coming back (recurrence) in patients with newly diagnosed stage I-II endometrial cancer. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. The addition of pembrolizumab to radiation treatment may be more effective than radiation treatment alone in reducing cancer recurrence.

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

The trial protocol does not specify whether you need to stop taking your current medications. However, it mentions that patients who have received any prohibited medications are excluded, so it's best to discuss your current medications with the trial team.

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

Research has shown that pembrolizumab, when combined with radiation therapy, has been studied for safety in treating endometrial cancer. In various studies, patients have generally tolerated pembrolizumab well. Most side effects, such as tiredness, nausea, and mild skin reactions, can be managed. However, some patients might experience more serious side effects, like inflammation of the lungs or liver, which are less common but important to monitor.

The FDA has already approved pembrolizumab for certain cancers, indicating that its safety is well-understood. The combination with radiation remains under study, but early results are promising regarding patient tolerance. It is essential to consult a healthcare provider about potential risks and benefits before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of pembrolizumab with radiation therapy for endometrial cancer because it introduces a novel approach to treatment. Unlike standard treatments that primarily rely on surgery and radiation, this investigational treatment combines immune checkpoint inhibition with pembrolizumab, which helps the immune system recognize and attack cancer cells more effectively. This combination could potentially enhance the overall effectiveness of radiation therapy by boosting the body's natural defenses against cancer. The use of pembrolizumab, which targets the PD-1/PD-L1 pathway, offers a promising new mechanism of action that is different from conventional therapies, providing hope for improved outcomes in patients with endometrial cancer.

What evidence suggests that this trial's treatments could be effective for endometrial cancer?

Research has shown that combining pembrolizumab with radiation therapy might reduce the chances of endometrial cancer returning. In this trial, participants in Arm II will receive pembrolizumab alongside radiation therapy. One study found that patients with advanced endometrial cancer who took pembrolizumab lived without their cancer worsening for an average of 13.1 months, compared to 8.7 months for those on a placebo. Additionally, 46% of patients responded positively to pembrolizumab, with their tumors shrinking or disappearing. This suggests that pembrolizumab, when combined with radiation, could be more effective than radiation alone, as in Arm I, in preventing cancer recurrence. ^{1 6 7 8 9}

Who Is on the Research Team?

Floor Backes

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

This trial is for patients with newly diagnosed stage I-II endometrioid endometrial cancer. They must have had specific imaging, surgery, and show no signs of disease outside the uterus. Eligible participants should not have received prior therapy for their cancer, meet certain health criteria, and be within a set time after initial surgery.

Inclusion Criteria

You need to have had a specific type of imaging that shows no signs of disease outside of the uterus.

My cancer shows signs of high microsatellite instability or lacks certain proteins.

I registered for the trial soon after my initial surgery.

Exclusion Criteria

I have an autoimmune disease that could come back and harm my organs.

I do not have any severe illnesses or social situations that would stop me from following the study's requirements.

I am currently in a clinical trial for endometrial cancer or was in one within the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Patients undergo pelvic external beam radiation therapy (EBRT) daily for 5-6 weeks and vaginal brachytherapy completed within 7 days after completion of EBRT

5-6 weeks

Daily visits for radiation therapy

Immunotherapy

Patients receive pembrolizumab intravenously every 6 weeks for up to 1 year (9 cycles) in the absence of disease progression or unacceptable toxicity

1 year

Every 6 weeks for pembrolizumab infusion

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Every 3 months for 2 years, then every 6 months for 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Brachytherapy
• External Beam Radiation Therapy
• Pembrolizumab

Trial Overview The study is testing if adding pembrolizumab (an immunotherapy drug) to usual radiation therapy reduces the risk of cancer recurrence better than radiation alone in early-stage high intermediate risk endometrial cancer.

How Is the Trial Designed?

Group I: Arm II (EBRT, brachytherapy, pembrolizumab) Experimental Treatment 9 Interventions

Patients undergo EBRT and brachytherapy as in Arm I. Within 7 days prior to the start of radiation therapy, patients also receive pembrolizumab IV over 30 minutes on day 1. Treatment with pembrolizumab repeats every 6 weeks for up to 1 year (9 cycles) in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples and CT scans, MRI scans, or x-ray imaging throughout the trial.

Group II: Arm I (EBRT, brachytherapy) Active Control 8 Interventions

Patients undergo pelvic EBRT daily for 5-6 weeks and vaginal brachytherapy completed within 7 days after completion of EBRT in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples and CT scans, MRI scans, or x-ray imaging throughout the trial.

Brachytherapy is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Brachytherapy for:

• Prostate cancer
• Cervical cancer
• Breast cancer
• Skin cancer
• Esophageal cancer

Approved in European Union as Brachytherapy for:

• Prostate cancer
• Cervical cancer
• Breast cancer
• Skin cancer
• Esophageal cancer
• Brain tumors

Approved in Canada as Brachytherapy for:

• Prostate cancer
• Cervical cancer
• Breast cancer
• Skin cancer
• Esophageal cancer

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

NRG Oncology

Collaborator

Trials

242

Recruited

105,000+

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]

High-dose rate electronic brachytherapy (EBT) is a feasible and safe option for postoperative adjuvant radiation therapy in endometrial cancer, with 41 patients treated and no reported recurrences during a median follow-up of 3.8 months.

Adverse events were mostly mild to moderate, with no severe complications in the EBT-only group, indicating a favorable safety profile for this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of electronic brachytherapy to deliver postsurgical adjuvant radiation therapy for endometrial cancer: a retrospective multicenter study. Dooley, WC., Thropay, JP., Schreiber, GJ., et al.[2021]

A study of 26 elderly women (median age 83) with endometrial cancer who were not surgical candidates showed that definitive radiation therapy, including external beam radiation and brachytherapy, is a feasible and well-tolerated treatment option.

The treatment resulted in an overall survival rate of 89% at 1 year and 73% at 3 years, with only 8% of patients experiencing late toxicity, indicating a favorable safety profile for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Definitive radiation therapy for endometrial cancer in medically inoperable elderly patients. Wegner, RE., Beriwal, S., Heron, DE., et al.[2010]

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]

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]

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]

In a study of 79 patients with early-stage endometrial cancer, the addition of pelvic radiotherapy to brachytherapy (EBRT-BT) resulted in a significant increase in acute toxicities, including a 37% rise in Grade 1-3 diarrhea and a 34% increase in lethargy compared to brachytherapy alone.

Despite the increased acute toxicities associated with EBRT-BT, all reported side effects resolved within three months post-treatment, highlighting the importance of patient counseling regarding potential risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant radiotherapy for endometrial cancer--a comparative review of radiotherapy technique with acute toxicity. Koh, YV., Tang, JI., Choo, BA., et al.[2020]

Postoperative external-beam pelvic radiotherapy (EBRT) increases the risk of death in low-risk endometrial cancer patients, suggesting it should not be used for this group.

For high-risk endometrial cancer, EBRT provides a significant disease-free survival advantage, benefiting about 10% of women, while also reducing the risk of pelvic recurrence across all invasive cancer types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival and recurrent disease after postoperative radiotherapy for early endometrial cancer: systematic review and meta-analysis. Johnson, N., Cornes, P.[2022]

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. 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. sciencedirect.com sciencedirect.com/science/article/pii/S0923753424000565

Adding immunotherapy to first-line treatment of advanced ... This trial assesses the efficacy and safety of first-line pembrolizumab plus lenvatinib versus paclitaxel plus carboplatin in patients with newly diagnosed ...

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 ...