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No longer recruiting (closed or complete)Last updated: 1 May 2025

Keynote-C93: This phase III trial is evaluating how safe and effective immunotherapy (pembrolizumab) compared to chemotherapy (carboplatin and paclitaxel) is in people with mismatch repair deficient (dMMR) advanced or recurrent endometrial cancer who have not had prior systemic therapyA Phase 3 Randomized, Open-label, Active-comparator Controlled Clinical Study of Pembrolizumab Versus Platinum Doublet Chemotherapy in Participants With Mismatch Repair Deficient (dMMR) Advanced or Recurrent Endometrial Carcinoma in the First-line Setting (KEYNOTE-C93/GOG-3064/ENGOT-en15)

Trial purpose

Medical clipboardCancer treatment

Tumor type

Female Reproductive System Cancers Gynaecological

Age

People18+

Trial acronym

Keynote-C93

Clinical summary

Summary

Eligible participants will be randomly allocated to either the Experimental Arm or Active Comparator Arm.

In the Experimental Arm, participants will receive pembrolizumab (400mg) via intravenous infusion (IV) on Day 1 of each 6-week cycle for up to 18 cycles (approximately 2 years).

In the Active Comparator Arm, participants will receive a combination of paclitaxel (175mg/m^2) on Day 1 of each 3-week cycle and carboplatin (AUC 5 or 6) on Day 1 of each 3-week cycle 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 (75mg/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 (75mg/m^2) in place of carboplatin on Day 1 Q3W after Sponsor consultation.

Conditions

This trial is treating people with endometrial cancer

Eligibility

Inclusion

The main inclusion and exclusion criteria include but are not limited to the following:

  • Has a histologically confirmed diagnosis of inoperable, Stage III or IV or recurrent Endometrial Carcinoma (EC) or carcinosarcoma (mixed Mullerian tumor) that is centrally confirmed as dMMR.
  • Has radiographically evaluable disease, either measurable or non-measurable per RECIST 1.1, as assessed by the investigator. Note: primary Stage IVB that has undergone surgical resection is allowed regardless of presence of measurable or evaluable disease.
  • Has received no prior systemic therapy for EC except for the following:

    1. May have received 1 prior line of systemic platinum-based adjuvant and/or neoadjuvant chemotherapy in the setting of curative-intent resection if the recurrence occurred ≥6 months after the last dose of chemotherapy.
    2. May have received prior radiation with or without radiosensitizing chemotherapy if >2 weeks before the start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
    3. May have received prior hormonal therapy for treatment of EC, provided that it was discontinued ≥1 week prior to randomization.
  • Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days before randomization.
  • Is not pregnant or breastfeeding and agrees to not donate eggs and use a highly effective contraceptive method for 120 days after the last dose of pembrolizumab or 180 days after the last dose of chemotherapy if a woman of childbearing potential (WOCBP).
  • Has a negative highly sensitive pregnancy test (urine or serum) within 24 hours for urine or 72 hours for serum before the first dose of study intervention if a WOCBP.
  • Provides an archival tumor tissue sample or newly obtained (core, incisional, or excisional) biopsy of a tumor lesion not previously irradiated for verification of dMMR status and histology.
  • Is Hepatitis B surface antigen (HBsAg) positive but has received Hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and has undetectable HBV viral load prior to randomization.
  • Has a history of Hepatitis C virus (HCV) infection but has undetectable HCV viral load at screening.

Exclusion

  • Has uterine mesenchymal tumor such as an endometrial stromal sarcoma, leiomyosarcoma, or other types of pure sarcomas. Adenosarcomas and neuroendocrine tumors are not allowed.
  • Has EC of any histology that is proficient mismatch repair (pMMR).
  • Is a candidate for curative-intent surgery or curative-intent radiotherapy.
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], Tumor necrosis factor receptor superfamily, member 4 [OX 40], tumor necrosis factor receptor superfamily member 9 [CD137]).
  • Has received prior systemic anticancer therapy including investigational agents for any advanced or metastatic EC. (Note: Prior chemotherapy administered as adjuvant therapy, neoadjuvant therapy, and/or concurrently with radiation is permitted.
  • Has had a major operation and has not recovered adequately from the procedure and/or any complications from the operation before starting study intervention.
  • Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed.
  • Is currently participating in or has participated in a study of an investigational agent for EC, has participated in a study of an investigational agent for non-EC within 4 weeks before the first dose of study intervention, or has used an investigational device within 4 weeks before the first dose of study intervention.
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention.
  • Has a known additional malignancy that is progressing or has required active treatment within the past 3 years with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (excluding carcinoma in situ of the bladder) that have undergone potentially curative therapy are not excluded.
  • Has known active CNS metastases and/or carcinomatous meningitis.
  • Has a known intolerance to any study intervention and/or any of its excipients.
  • Has an active autoimmune disease that has required systemic treatment in past 2 years.
  • Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
  • Has an active infection, requiring systemic therapy.
  • Has a known history of human immunodeficiency virus (HIV) infection.
  • Has had an allogenic tissue/solid organ transplant.

Inclusion

  • Your cancer has spread to other parts of the body (metastatic) or has grown into nearby parts of the body (locally advanced).
  • Your cancer has not spread to other parts of the body (localised).

Exclusion

  • You have certain types of non-cancer medical conditions.
  • You have had certain treatments, surgical procedures or drugs.
  • You are currently being treated on a clinical trial.
Message

Clinical trials have complex eligibility criteria, and other criteria may apply for this trial. Ask your doctor about whether this trial could be right for you.

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More information

Trial Identifiers

Information on this page is partially produced from ClinicalTrials.gov *. View further details about this trial on the registry via the links below:

Trial sponsor

Merck, European Network of Gynaecological Oncological Trial Groups (ENGOT)

Scientific Title

A Phase 3 Randomized, Open-label, Active-comparator Controlled Clinical Study of Pembrolizumab Versus Platinum Doublet Chemotherapy in Participants With Mismatch Repair Deficient (dMMR) Advanced or Recurrent Endometrial Carcinoma in the First-line Setting (KEYNOTE-C93/GOG-3064/ENGOT-en15)

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