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History of Changes for Study: NCT05173987
Study of Pembrolizumab (MK-3475) Versus Chemotherapy in Mismatch Repair Deficient (dMMR) Advanced or Recurrent Endometrial Carcinoma (MK-3475-C93/KEYNOTE-C93/GOG-3064/ENGOT-en15)
Latest version (submitted November 11, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 December 20, 2021 None (earliest Version on record)
2 February 4, 2022 Recruitment Status, Study Status, Contacts/Locations and Study Identification
3 March 17, 2022 Study Status and Contacts/Locations
4 March 25, 2022 Contacts/Locations and Study Status
5 April 7, 2022 Study Status and Contacts/Locations
6 April 13, 2022 Contacts/Locations and Study Status
7 April 21, 2022 Contacts/Locations and Study Status
8 April 28, 2022 Contacts/Locations and Study Status
9 May 13, 2022 Study Status and Contacts/Locations
10 May 26, 2022 Contacts/Locations, Eligibility and Study Status
11 June 9, 2022 Study Status and Contacts/Locations
12 June 23, 2022 Contacts/Locations and Study Status
13 July 15, 2022 Contacts/Locations and Study Status
14 July 25, 2022 Contacts/Locations and Study Status
15 July 29, 2022 Contacts/Locations and Study Status
16 August 11, 2022 Contacts/Locations and Study Status
17 August 22, 2022 Contacts/Locations and Study Status
18 September 2, 2022 Contacts/Locations and Study Status
19 September 15, 2022 Contacts/Locations and Study Status
20 September 26, 2022 Contacts/Locations and Study Status
21 October 17, 2022 Contacts/Locations, Study Status, References, Eligibility and Outcome Measures
22 November 6, 2022 Contacts/Locations and Study Status
23 November 11, 2022 Contacts/Locations and Study Status
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Study NCT05173987
Submitted Date:  December 20, 2021 (v1)

Open or close this module Study Identification
Unique Protocol ID: 3475-C93
Brief Title: Study of Pembrolizumab (MK-3475) Versus Chemotherapy in Mismatch Repair Deficient (dMMR) Advanced or Recurrent Endometrial Carcinoma (MK-3475-C93/KEYNOTE-C93/GOG-3064/ENGOT-en15)
Official 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)
Secondary IDs: 2021-003185-12 [EudraCT Number]
MK-3475-C93 [Merck]
KEYNOTE-C93 [Merck]
GOG-3064 [Gynecologic Oncology Group]
ENGOT-en15 [European Network of Gynaecological Oncological Trial Groups (ENGOT)]
Open or close this module Study Status
Record Verification: December 2021
Overall Status: Not yet recruiting
Study Start: January 25, 2022
Primary Completion: July 17, 2026 [Anticipated]
Study Completion: July 17, 2026 [Anticipated]
First Submitted: December 20, 2021
First Submitted that
Met QC Criteria:
December 20, 2021
First Posted: December 30, 2021 [Actual]
Last Update Submitted that
Met QC Criteria:
December 20, 2021
Last Update Posted: December 30, 2021 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Merck Sharp & Dohme LLC
Responsible Party: Sponsor
Collaborators: European Network of Gynaecological Oncological Trial Groups (ENGOT)
Gynecologic Oncology Group
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
Brief Summary:

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).

Detailed Description:
Open or close this module Conditions
Conditions: Endometrial Neoplasms
Keywords: Programmed Cell Death-1 (PD1, PD-1)
Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1)
Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 3
Interventional Study Model: Parallel Assignment
Number of Arms: 2
Masking: None (Open Label)
Allocation: Randomized
Enrollment: 350 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Pembrolizumab
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).
Biological: pembrolizumab
Intravenous (IV) infusion
Other Names:
  • KEYTRUDA®
  • MK-3475
Active Comparator: Carboplatin+paclitaxel
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.
Drug: carboplatin
IV infusion
Other Names:
  • PARAPLATIN®
Drug: paclitaxel
IV infusion
Other Names:
  • TAXOL®
Drug: docetaxel
IV infusion
Other Names:
  • TAXOTERE®
Drug: cisplatin
IV infusion
Other Names:
  • PLATINOL-AQ®
Open or close this module Outcome Measures
Primary Outcome Measures:
1. 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)
[ Time Frame: Up to approximately 30 months ]

PFS is defined as the time from randomization to the first documented disease progression (PD) per RECIST 1.1 or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more lesions and the unequivocal progression of non-target lesions is also considered PD. The PFS per RECIST 1.1 as assessed by BICR will be reported for participants.
2. Overall Survival
[ Time Frame: Up to approximately 49 months ]

OS is defined as the time from randomization to death due to any cause. The OS will be reported for all participants.
Secondary Outcome Measures:
1. Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
[ Time Frame: Up to approximately 30 months ]

ORR is defined as the percentage of participants who have a best response of confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The percentage of participants who experience CR or PR as assessed by BICR will be presented.
2. Disease Control Rate (DCR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
[ Time Frame: Up to approximately 30 months ]

DCR is defined, per RECIST 1.1, as the percentage of participants who have achieved Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) or demonstrated Stable Disease (SD) for at least 24 weeks. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD.) The DCR as assessed by BICR will be presented.
3. Duration of Response (DOR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
[ Time Frame: Up to approximately 30 months ]

DOR is defined as the time from first documented evidence of CR or PR until the first documented date of disease progression (PD) or death due to any cause, whichever occurs first, for participants who demonstrate a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR as assessed by BICR will be presented.
4. Progression-Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator
[ Time Frame: Up to approximately 30 months ]

PFS is defined as the time from randomization to the first documented disease progression (PD) per RECIST 1.1 or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more lesions and the unequivocal progression of non-target lesions is also considered PD. The PFS per RECIST 1.1 as assessed by investigator will be reported for participants.
5. Progression-Free Survival 2 (PFS2) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator
[ Time Frame: Up to approximately 30 months ]

PFS2 is defined as the time from randomization to subsequent disease progression (PD) per RECIST 1.1 after initiation of a new anticancer therapy, or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more lesions and the unequivocal progression of non-target lesions is also considered PD. The PFS2 per RECIST 1.1 as assessed by investigator will be reported for participants.
6. Number of Participants Who Experience at Least One Adverse Event (AE)
[ Time Frame: Up to approximately 27 months ]

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experience an AE will be reported.
7. Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)
[ Time Frame: Up to approximately 24 months ]

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinue study treatment due to an AE will be reported.
8. Change From Baseline in European Organization for Research And Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status (GHS) (Item 29) And Quality of Life (QoL) (Item 30) Combined Score
[ Time Frame: Baseline and up to approximately 25 months ]

The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?" are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status. The change from baseline in EORTC QLQ-C30 Items 29 and 30 combined score will be presented.
9. Change From Baseline in European Organization for Research And Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Physical Functioning (Items 1-5) Combined Score
[ Time Frame: Baseline and up to approximately 25 months ]

The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in Physical Functioning (EORTC QLQ-C30 Items 1-5) score will be presented. A higher score indicates a better quality of life.
10. Time to Deterioration (TTD) in European Organization for Research And Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status (GHS) (Item 29) And Quality of Life (QoL) (Item 30) Combined Score
[ Time Frame: Up to approximately 25 months ]

TTD is defined as the time from baseline to the first onset of a ≥10-point deterioration (decrease) from baseline in EORTC QLQ-C30 GHS (Item 29) and QoL (Item 30) combined score. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point negative change (decrease) from baseline, in combined GHS (Item 29 and QoL (Item 30) score will be presented. A longer TTD indicates a better outcome.
11. Time to Deterioration (TTD) in European Organization for Research And Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Physical Functioning (Items 1-5) Combined Score
[ Time Frame: Up to approximately 25 months ]

TTD is defined as the time from baseline to the first onset of a ≥10-point deterioration (decrease) from baseline in EORTC QLQ-C30 physical functioning (Items 1-5) combined score. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point negative change (decrease) from baseline, in combined GHS (Item 29 and QoL (Item 30) score will be presented. A longer TTD indicates a better outcome.
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: Female
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

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

Inclusion Criteria:

  • Has a histologically confirmed diagnosis of Stage III or IV or recurrent Endometrial Carcinoma (EC) or carcinosarcoma (mixed Mullerian tumor) that is centrally confirmed as dMMR
  • Has received no prior systemic therapy for advanced EC except for the following:
    1. 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
    2. 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 Criteria:

  • 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 EC. This includes any chemotherapy given for EC other than as a radiosensitizer
  • 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
Open or close this module Contacts/Locations
Study Officials: Medical Director
Study Director
Merck Sharp & Dohme LLC
Locations:
Open or close this module IPDSharing
Plan to Share IPD: Yes
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Supporting Information:
Time Frame:
Access Criteria:
URL: http://engagezone.msd.com/ds_documentation.php
Open or close this module References
Citations:
Links:
Available IPD/Information:

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