Immunotherapy vs Chemotherapy for Endometrial Cancer

Recruiting at 196 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, Anti-PD-1

Disqualifiers: Immunodeficiency, Active infection, Autoimmune, 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: Unknown

Duration: Up to approximately 24 months

280 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to assess the safety and efficacy of treatment with pembrolizumab (MK-3475) compared to a combination of carboplatin and paclitaxel in women with mismatch repair deficient (dMMR) advanced or recurrent endometrial carcinoma who have not previously been treated with prior systemic chemotherapy. The primary study hypotheses are that pembrolizumab is superior to the combination of carboplatin and paclitaxel with respect to Progression Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR) and Overall Survival (OS).

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic steroid therapy or any form of immunosuppressive therapy, you must stop these at least 7 days before starting the study treatment.

What data supports the effectiveness of the drug combination of pembrolizumab, carboplatin, and paclitaxel for endometrial cancer?

Research suggests that adding immunotherapy, like pembrolizumab, to standard chemotherapy drugs carboplatin and paclitaxel might improve outcomes for patients with advanced or recurrent endometrial cancer, although the exact benefits are still being studied. ^{1 2 3 4 5}

Is the combination of carboplatin, paclitaxel, and pembrolizumab safe for humans?

Research shows that carboplatin and paclitaxel, often used together for treating endometrial cancer, have known safety profiles, but the safety of adding pembrolizumab (an immunotherapy drug) is still being studied. These treatments have been used in various conditions, and while they can have side effects, they are generally considered safe for human use. ^{1 2 3 6 7}

How is the drug combination of Carboplatin, Paclitaxel, and Pembrolizumab different from other treatments for endometrial cancer?

This drug combination is unique because it adds pembrolizumab, an immunotherapy drug, to the standard chemotherapy drugs carboplatin and paclitaxel, potentially enhancing the body's immune response against cancer cells. While the standard treatment involves only chemotherapy, the addition of pembrolizumab aims to improve outcomes by leveraging the immune system, although its benefits are still being studied. ^{1 2 3 8 9}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for women with advanced or recurrent endometrial carcinoma that's mismatch repair deficient (dMMR) and who haven't had systemic chemotherapy before. They should be in good physical condition, not pregnant, willing to use contraception, and able to provide a tumor tissue sample. Those with active CNS metastases, recent major surgeries, other cancers within 3 years (except certain skin cancers), active infections requiring therapy, HIV infection or autoimmune diseases treated in the last 2 years can't join.

Inclusion Criteria

I am positive for Hepatitis B but have been treated and now have an undetectable viral load.

My cancer can be seen and measured on scans.

I have esophageal cancer and have only had specific prior treatments like chemotherapy, radiation, or hormonal therapy.

Exclusion Criteria

Is currently participating in or has participated in certain types of studies or used investigational devices within specified timeframes before the first dose of study intervention.

I have had treatment for advanced or metastatic endometrial cancer.

I am still recovering from a major surgery.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab 400 mg via IV infusion on Day 1 of each 6-week cycle for up to 18 cycles or a combination of paclitaxel and carboplatin for 6 cycles

Up to approximately 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 59 months

Treatment Details

Interventions

• Carboplatin
• Paclitaxel
• Pembrolizumab

Trial Overview The study compares the safety and effectiveness of pembrolizumab against standard chemotherapy (carboplatin and paclitaxel). The goal is to see if pembrolizumab improves progression-free survival and overall survival better than the chemo combination. Participants will be randomly assigned to one of these treatments.

Participant Groups

Group I: Pembrolizumab Experimental Treatment 1 Intervention

Participants receive pembrolizumab 400 mg via IV infusion on Day 1 of each 6-week cycle (Q6W) for up to 18 cycles (up to approximately 2 years).

Group II: Carboplatin+paclitaxel Active Control 4 Interventions

Participants receive a combination of paclitaxel 175 mg/m\^2 on Day 1 of each 3-week cycle (Q3W) and carboplatin AUC 5 or 6 on Day 1 Q3W for 6 cycles (up to approximately 4 months). Participants who experience a severe hypersensitivity reaction to paclitaxel or an adverse event (AE) requiring discontinuation of paclitaxel may receive docetaxel 75 mg/m\^2 in place of paclitaxel on Day 1 Q3W after Sponsor consultation. Participants who experience a severe hypersensitivity reaction to carboplatin or an AE requiring discontinuation of carboplatin may receive cisplatin 75 mg/m\^2 in place of carboplatin on Day 1 Q3W after Sponsor consultation.

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

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

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

GOG Foundation

Collaborator

Trials

48

Recruited

18,500+

European Network of Gynaecological Oncological Trial Groups (ENGOT)

Collaborator

Trials

41

Recruited

19,200+

Gynecologic Oncology Group

Collaborator

Trials

251

Recruited

65,400+

Findings from Research

In a review of three studies involving 1,431 patients, the addition of PD-1/PD-L1 inhibitors to standard chemotherapy (carboplatin and paclitaxel) significantly improved progression-free survival (PFS) and overall survival (OS) in patients with mismatch repair-deficient endometrial cancer.

However, this benefit was not observed in patients with mismatch repair-proficient tumors, indicating that the effectiveness of the combination therapy may depend on the specific genetic characteristics of the cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-1/PD-L1 inhibitors plus carboplatin and paclitaxel compared with carboplatin and paclitaxel in primary advanced or recurrent endometrial cancer: a systematic review and meta-analysis of randomized clinical trials. de Moraes, FCA., Pasqualotto, E., Lopes, LM., et al.[2023]

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 a phase 2 trial involving 125 women with advanced or recurrent endometrial cancer, adding avelumab to standard chemotherapy (carboplatin and paclitaxel) showed a similar median progression-free survival of 9.6 months compared to 9.9 months for chemotherapy alone, suggesting no significant improvement in efficacy.

However, the experimental group receiving avelumab experienced more serious adverse events, indicating potential safety concerns that need to be addressed in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin and paclitaxel plus avelumab compared with carboplatin and paclitaxel in advanced or recurrent endometrial cancer (MITO END-3): a multicentre, open-label, randomised, controlled, phase 2 trial. Pignata, S., Scambia, G., Schettino, C., et al.[2023]

In a study of 122 patients with high and intermediate-high risk endometrial cancer, those treated with a dose dense regimen of paclitaxel plus carboplatin showed a significantly higher three-year progression-free survival (79.5%) compared to those on the standard three-weekly protocol (57.4%).

The dose dense protocol also resulted in fewer progression events and distant metastases, along with improved overall survival in advanced stage cases, while experiencing fewer complaints of musculoskeletal pain compared to the standard treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose dense carboplatin paclitaxel improves progression free survival in patients with endometrial cancer. Kogan, L., Laskov, I., Amajoud, Z., 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]

In a study of 37 patients with advanced or recurrent endometrial carcinoma, the combination of paclitaxel and carboplatin resulted in a 61% objective response rate, including one complete response and ten partial responses, indicating its efficacy in treating this cancer.

While the treatment was effective, it was associated with significant hematologic toxicity, with 59% of patients experiencing grade 3 or 4 leukopenia and 86% experiencing neutropenia, highlighting the need for monitoring and potential supportive care during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment with paclitaxel plus carboplatin, alone or with irradiation, of advanced or recurrent endometrial carcinoma. Arimoto, T., Nakagawa, S., Yasugi, T., et al.[2015]

In a study of 18 patients with advanced or recurrent endometrial cancer, the combination of carboplatin and paclitaxel showed a high overall response rate of 63%, with 35% achieving a complete response.

The treatment demonstrated minimal toxicity, as no patients experienced severe side effects like neutropenia or significant vomiting, and the median survival time was 27 months, indicating it is a promising option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin and paclitaxel for the treatment of advanced or recurrent endometrial cancer. Akram, T., Maseelall, P., Fanning, J.[2015]

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]

Checkpoint inhibitors like pembrolizumab and dostarlimab have become important treatment options for endometrial carcinoma, particularly for tumors that are mismatch repair deficient or have a high mutational load.

The review highlights the need for personalized immunotherapy approaches based on the distinct molecular subtypes of endometrial cancer, as these subtypes exhibit different characteristics that could influence treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Facts and Hopes in Immunotherapy of Endometrial Cancer. Marín-Jiménez, JA., García-Mulero, S., Matías-Guiu, X., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

PD-1/PD-L1 inhibitors plus carboplatin and paclitaxel compared with carboplatin and paclitaxel in primary advanced or recurrent endometrial cancer: a systematic review and meta-analysis of randomized clinical trials. [2023]

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

Pembrolizumab plus Chemotherapy in Advanced Endometrial Cancer. [2023]

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

Carboplatin and paclitaxel plus avelumab compared with carboplatin and paclitaxel in advanced or recurrent endometrial cancer (MITO END-3): a multicentre, open-label, randomised, controlled, phase 2 trial. [2023]

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

Dose dense carboplatin paclitaxel improves progression free survival in patients with endometrial cancer. [2022]

5. United States 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. [2023]

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

Treatment with paclitaxel plus carboplatin, alone or with irradiation, of advanced or recurrent endometrial carcinoma. [2015]

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

Carboplatin and paclitaxel for the treatment of advanced or recurrent endometrial cancer. [2015]

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

New Approved Use for Keytruda. [2022]

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

Facts and Hopes in Immunotherapy of Endometrial Cancer. [2023]