Clinical Trials List
Protocol NumberMK-3475-B21
NCT Number(ClinicalTrials.gov Identfier)NCT04634877
2020-11-16 - 2026-03-31
Phase III
Not yet recruiting5
ICD-10C54.1
Malignant neoplasm of endometrium
ICD-10C54.2
Malignant neoplasm of myometrium
ICD-10C54.3
Malignant neoplasm of fundus uteri
ICD-10C54.9
Malignant neoplasm of corpus uteri, unspecified
ICD-10Z51.12
Encounter for antineoplastic immunotherapy
ICD-9182.0
Malignant neoplasm of corpus uteri, except isthmus
A Phase 3, Randomized, Double-Blind Study of Pembrolizumab versus Placebo in Combination With Adjuvant Chemotherapy With or Without Radiotherapy for the Treatment of Newly Diagnosed High-Risk Endometrial Cancer After Surgery With Curative Intent (KEYNOTE-B21 / ENGOT-en11 / GOG-3053).
-
Trial Applicant
Merck Sharp & Dohme (I.A.) LLC
-
Sponsor
Merck Sharp & Dohme LLC
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Yen-Hou Chang 未分科
- 陳蓉萱 未分科
- Huann-Cheng Horng 無
- 胡育文 無
- 沈書慧 無
- 陳蓉宣 未分科
- Yi-Jen Chen 無
- Yu-Ming Liu 未分科
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
- 容世明 無
- Gigin Lin 無
- 黃意婷 無
- 周宏學 無
- Ting-Chang Chang 無
- Angel Chao 無
- Yun-Hsin Tang 無
- Huei-Jean Huang 無
- 周宏學 未分科
- 陳威君 無
- 黃寬仁 無
- Cheng-Tao Lin 無
- 黃彥綾 無
- 吳仁欽 無
- HSIU-JUNG TUNG 無
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Condition/Disease
Endometrial Cancer
Objectives
In women with persistent, recurrent, or metastatic cervical cancer treated with pembrolizumab plus chemotherapy versus placebo plus chemotherapy: The study will be considered positive if it is positive for either the PFS or OS hypothesis test for any of the 3 groups (CPS ≥10 group, CPS ≥1 group, and all-comers).
Test Drug
pembrolizumab
Active Ingredient
Pembrolizumab
Dosage Form
Injection
Dosage
100 mg/ 4 mL
Endpoints
PFS: The time from randomization to the first documented disease progression or death due to any cause, whichever occurs first
OS: The time from randomization to death due to any cause
OS: The time from randomization to death due to any cause
Inclution Criteria
Participants are eligible to be included in the study only if all of the following
criteria apply:
1. Female participants who are at least 18 years of age on the day of signing
informed consent.
2. Have persistent, recurrent, or metastatic squamous cell carcinoma,
adenosquamous carcinoma, or adenocarcinoma of the cervix which has not
been treated with systemic chemotherapy and is not amenable to curative
treatment (such as with surgery and/or radiation).
NOTE: Prior chemotherapy utilized as a radiosensitizing agent and completed
at least 2 weeks prior to randomization with resolution of all radiation-related
toxicities is allowed.
3. Not be pregnant (Protocol Appendix 5) or breastfeeding, and at least one of
the following conditions applies:
a. Not be a woman of childbearing potential (WOCBP) as defined in
Protocol Appendix 5 or
b. A WOCBP must agree to follow the contraceptive guidance in Protocol
Appendix 5 during the treatment period and for at least 120 days after
the last dose of pembrolizumab/placebo or 210 days after the last dose of
chemotherapy.
Note: Abstinence is acceptable if this is the usual lifestyle and preferred
contraception for the participant.Informed Consent
4. The participant (or legally acceptable representative if applicable) provides
written informed consent for the study. The participant may also provide
consent for future biomedical research. However, the participant may
participate in the main study without participating in future biomedical
research.
Additional Categories
5. Have measurable disease per RECIST 1.1 as assessed by the local site
investigator/radiology. Lesions situated in a previously irradiated area are
considered measurable only if progression has been demonstrated in such
lesions.
6. Have provided archival tumor tissue sample or newly obtained core or
excisional biopsy of a tumor lesion not previously irradiated for prospective
determination of PD-L1 status prior to randomization.
Note: Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred
to slides. Newly obtained biopsies are preferred to archived tissue. If
submitting unstained cut slides, newly cut slides should be submitted to the
testing laboratory within 14 days from the date slides are cut (details
pertaining to tumor tissue submission can be found in the Laboratory
Manual).
7. Have an Eastern Cooperative Oncology Group (ECOG) performance status of
0 to 1 within 14 days prior to randomization.
8. Have adequate organ function as indicated by the following laboratory values
within 14 days prior to randomization
criteria apply:
1. Female participants who are at least 18 years of age on the day of signing
informed consent.
2. Have persistent, recurrent, or metastatic squamous cell carcinoma,
adenosquamous carcinoma, or adenocarcinoma of the cervix which has not
been treated with systemic chemotherapy and is not amenable to curative
treatment (such as with surgery and/or radiation).
NOTE: Prior chemotherapy utilized as a radiosensitizing agent and completed
at least 2 weeks prior to randomization with resolution of all radiation-related
toxicities is allowed.
3. Not be pregnant (Protocol Appendix 5) or breastfeeding, and at least one of
the following conditions applies:
a. Not be a woman of childbearing potential (WOCBP) as defined in
Protocol Appendix 5 or
b. A WOCBP must agree to follow the contraceptive guidance in Protocol
Appendix 5 during the treatment period and for at least 120 days after
the last dose of pembrolizumab/placebo or 210 days after the last dose of
chemotherapy.
Note: Abstinence is acceptable if this is the usual lifestyle and preferred
contraception for the participant.Informed Consent
4. The participant (or legally acceptable representative if applicable) provides
written informed consent for the study. The participant may also provide
consent for future biomedical research. However, the participant may
participate in the main study without participating in future biomedical
research.
Additional Categories
5. Have measurable disease per RECIST 1.1 as assessed by the local site
investigator/radiology. Lesions situated in a previously irradiated area are
considered measurable only if progression has been demonstrated in such
lesions.
6. Have provided archival tumor tissue sample or newly obtained core or
excisional biopsy of a tumor lesion not previously irradiated for prospective
determination of PD-L1 status prior to randomization.
Note: Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred
to slides. Newly obtained biopsies are preferred to archived tissue. If
submitting unstained cut slides, newly cut slides should be submitted to the
testing laboratory within 14 days from the date slides are cut (details
pertaining to tumor tissue submission can be found in the Laboratory
Manual).
7. Have an Eastern Cooperative Oncology Group (ECOG) performance status of
0 to 1 within 14 days prior to randomization.
8. Have adequate organ function as indicated by the following laboratory values
within 14 days prior to randomization
Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
1. A WOCBP who has a positive urine pregnancy test within 72 hours prior to
randomization (see Protocol Appendix 5). If the urine test is positive or
cannot be confirmed as negative, a serum pregnancy test will be required.
Note: In the event that 72 hours have elapsed between the pregnancy test and
the first dose of study treatment, another pregnancy test (urine or serum) must
be performed and must be negative in order for participant to start receiving
study medication.
2. Has known active CNS metastases and/or carcinomatous meningitis.
Participants with known brain metastases may participate provided that the brain metastases have been previously treated (except with chemotherapy)
and are radiographically stable. To demonstrate radiographic stability of
previously treated brain metastases, a minimum of 2 post-treatment brain
imaging assessments are required: 1) The first brain imaging must be acquired
after treatment of brain metastases has been completed 2) The second brain
imaging must be obtained during screening (i.e. within 28 days prior to
randomization) and >4 weeks after the previous post-treatment brain imaging.
Note: Known brain metastases are considered active, if any of the following
criteria are applicable:
a. Brain imaging during screening demonstrates progression of existing
metastases and/or appearance of new lesions compared to brain imaging
performed at least 4 weeks earlier.
Radiographic stability of previously treated brain metastases is based on
local radiology/investigator review, but dated reports of 2 imaging
studies (the most recent performed during screening) documenting
stability of brain metastasis(es) over ≥4 weeks must be available at the
site for submission to the central imaging vendor, if later needed.
b. Neurological symptoms attributed to brain metastases have not returned
to baseline
c. Steroids were used for management of symptoms related to brain
metastases within 28 days prior to randomization
3. Has a known additional malignancy that is progressing or has required active
treatment within the past 3 years.
Note: Participants with basal cell carcinoma of the skin, squamous cell
carcinoma of the skin, transitional cell carcinoma of urothelial cancer, or
carcinoma in situ (eg, breast cancer) that have undergone potentially curative
therapy are not excluded
4. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid
therapy (in doses exceeding 10 mg daily of prednisone equivalent) or any
other form of immunosuppressive therapy within 7 days prior to
randomization.
5. Has an active autoimmune disease that has required systemic treatment in past
2 years (ie, with use of disease modifying agents, corticosteroids or
immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or
physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency) is not considered a form of systemic treatment and is allowed.
6. Has a history of (non-infectious) pneumonitis that required steroids or hascurrent pneumonitis.
7. Has an active infection requiring systemic therapy.
8. Has a known history of human immunodeficiency virus (HIV) infection.
Note: No testing for HIV is required unless mandated by local health
authority.
9. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen
[HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA
[qualitative] is detected) infection.
Note: No testing for Hepatitis B and Hepatitis C is required unless mandated
by local health authority.
10. Has a known history of active tuberculosis (TB; Bacillus tuberculosis).
Prior/Concomitant Therapy
11. 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 co-inhibitory T-cell
receptor (eg, CTLA-4, OX 40, CD137).
12. Has received prior systemic chemotherapy for treatment of cervical cancer
(chemotherapy used as a radiosensitizing agent and completed at least 2
weeks prior to randomization is permitted).
13. Has not recovered adequately from toxicity and/or complications from
surgery prior to randomization.
14. Has received prior radiotherapy within 2 weeks prior to randomization.
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-CNS disease.
15. Has received a live vaccine within 30 days prior to randomization. Examples
of live vaccines include, but are not limited to, the following: measles,
mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus
Calmette–Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines
for injection are generally killed virus vaccines and are allowed; however,
intranasal influenza vaccines (eg, FluMist® ) are live attenuated vaccines and
are not allowed.
16. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its
excipients.
17. Has a contraindication or hypersensitivity to any component of cisplatin,
carboplatin, paclitaxel, or bevacizumab. NOTE: Investigators must use the
local label for contraindications, prohibited medications, and precautions foruse.
Prior/Concurrent Clinical Study Experience
18. Is currently participating in or has participated in a study of an investigational
agent or has used an investigational device within 4 weeks prior to
randomization.
Note: Participants who have entered the follow-up phase of an investigational
study may participate as long as it has been 4 weeks after the last dose of the
previous investigational agent.
Other Exclusions
19. Is pregnant or breastfeeding or expecting to conceive within the projected
duration of the study, starting with the screening visit through 120 days
following last dose of pembrolizumab/placebo and 210 days following last
dose of chemotherapy.
20. Has had an allogeneic tissue/solid organ transplant.
21. Has a known psychiatric or substance abuse disorder that would interfere with
cooperating with the requirements of the study.
22. Has a history or current evidence of any condition, therapy, or laboratory
abnormality that might confound the results of the study, interfere with the
participant's participation for the full duration of the study, or is not in the
best interest of the participant to participate, in the opinion of the treating
investigator.
Medical Conditions
1. A WOCBP who has a positive urine pregnancy test within 72 hours prior to
randomization (see Protocol Appendix 5). If the urine test is positive or
cannot be confirmed as negative, a serum pregnancy test will be required.
Note: In the event that 72 hours have elapsed between the pregnancy test and
the first dose of study treatment, another pregnancy test (urine or serum) must
be performed and must be negative in order for participant to start receiving
study medication.
2. Has known active CNS metastases and/or carcinomatous meningitis.
Participants with known brain metastases may participate provided that the brain metastases have been previously treated (except with chemotherapy)
and are radiographically stable. To demonstrate radiographic stability of
previously treated brain metastases, a minimum of 2 post-treatment brain
imaging assessments are required: 1) The first brain imaging must be acquired
after treatment of brain metastases has been completed 2) The second brain
imaging must be obtained during screening (i.e. within 28 days prior to
randomization) and >4 weeks after the previous post-treatment brain imaging.
Note: Known brain metastases are considered active, if any of the following
criteria are applicable:
a. Brain imaging during screening demonstrates progression of existing
metastases and/or appearance of new lesions compared to brain imaging
performed at least 4 weeks earlier.
Radiographic stability of previously treated brain metastases is based on
local radiology/investigator review, but dated reports of 2 imaging
studies (the most recent performed during screening) documenting
stability of brain metastasis(es) over ≥4 weeks must be available at the
site for submission to the central imaging vendor, if later needed.
b. Neurological symptoms attributed to brain metastases have not returned
to baseline
c. Steroids were used for management of symptoms related to brain
metastases within 28 days prior to randomization
3. Has a known additional malignancy that is progressing or has required active
treatment within the past 3 years.
Note: Participants with basal cell carcinoma of the skin, squamous cell
carcinoma of the skin, transitional cell carcinoma of urothelial cancer, or
carcinoma in situ (eg, breast cancer) that have undergone potentially curative
therapy are not excluded
4. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid
therapy (in doses exceeding 10 mg daily of prednisone equivalent) or any
other form of immunosuppressive therapy within 7 days prior to
randomization.
5. Has an active autoimmune disease that has required systemic treatment in past
2 years (ie, with use of disease modifying agents, corticosteroids or
immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or
physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency) is not considered a form of systemic treatment and is allowed.
6. Has a history of (non-infectious) pneumonitis that required steroids or hascurrent pneumonitis.
7. Has an active infection requiring systemic therapy.
8. Has a known history of human immunodeficiency virus (HIV) infection.
Note: No testing for HIV is required unless mandated by local health
authority.
9. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen
[HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA
[qualitative] is detected) infection.
Note: No testing for Hepatitis B and Hepatitis C is required unless mandated
by local health authority.
10. Has a known history of active tuberculosis (TB; Bacillus tuberculosis).
Prior/Concomitant Therapy
11. 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 co-inhibitory T-cell
receptor (eg, CTLA-4, OX 40, CD137).
12. Has received prior systemic chemotherapy for treatment of cervical cancer
(chemotherapy used as a radiosensitizing agent and completed at least 2
weeks prior to randomization is permitted).
13. Has not recovered adequately from toxicity and/or complications from
surgery prior to randomization.
14. Has received prior radiotherapy within 2 weeks prior to randomization.
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-CNS disease.
15. Has received a live vaccine within 30 days prior to randomization. Examples
of live vaccines include, but are not limited to, the following: measles,
mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus
Calmette–Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines
for injection are generally killed virus vaccines and are allowed; however,
intranasal influenza vaccines (eg, FluMist® ) are live attenuated vaccines and
are not allowed.
16. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its
excipients.
17. Has a contraindication or hypersensitivity to any component of cisplatin,
carboplatin, paclitaxel, or bevacizumab. NOTE: Investigators must use the
local label for contraindications, prohibited medications, and precautions foruse.
Prior/Concurrent Clinical Study Experience
18. Is currently participating in or has participated in a study of an investigational
agent or has used an investigational device within 4 weeks prior to
randomization.
Note: Participants who have entered the follow-up phase of an investigational
study may participate as long as it has been 4 weeks after the last dose of the
previous investigational agent.
Other Exclusions
19. Is pregnant or breastfeeding or expecting to conceive within the projected
duration of the study, starting with the screening visit through 120 days
following last dose of pembrolizumab/placebo and 210 days following last
dose of chemotherapy.
20. Has had an allogeneic tissue/solid organ transplant.
21. Has a known psychiatric or substance abuse disorder that would interfere with
cooperating with the requirements of the study.
22. Has a history or current evidence of any condition, therapy, or laboratory
abnormality that might confound the results of the study, interfere with the
participant's participation for the full duration of the study, or is not in the
best interest of the participant to participate, in the opinion of the treating
investigator.
The Estimated Number of Participants
-
Taiwan
35 participants
-
Global
990 participants
