Clinical Trials List
Protocol NumberMK3475-564
NCT Number(ClinicalTrials.gov Identfier)NCT03142334
Active
2017-06-01 - 2026-12-31
Phase III
Terminated5
ICD-10C64
Malignant neoplasm of kidney, except renal pelvis
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Pembrolizumab (MK-3475) as Monotherapy in the Adjuvant Treatment of Renal Cell Carcinoma Post Nephrectomy (KEYNOTE-564)
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Trial Applicant
Merck Sharp & Dohme (I.A.) LLC
-
Sponsor
Merck Sharp & Dohme Corp.
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Trial scale
Multi-Regional Multi-Center
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Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- Hsiao-Jen Chung Division of Radiology
- Yen-Hwa Chang Division of Radiology
- 潘競成 Division of Urology
- 沈書慧 Division of Radiology
- Tzu-Ping Lin Division of Urology
- Yi-Hsiu Huang Division of Radiology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Hsi-Chin Wu Division of Radiation Therapy
- Chi-Rei Yang Division of Radiation Therapy
- Ching-Chan Lin Division of Radiation Therapy
- 陳冠亨 Division of Radiation Therapy
- Su-Peng Yeh Division of Radiation Therapy
- Wei-Ching Lin Division of Radiation Therapy
- Chi-Ping Huang Division of Radiation Therapy
- Che-Hung Lin Division of Radiation Therapy
- Yi-Huei Chang Division of Radiation Therapy
- Po-Fan Hsieh Division of Radiation Therapy
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Chuan-Shu Chen Division of Urology
- 洪晟鈞 Division of Urology
- Cheng-Che Chen Division of Urology
- 裘坤元 Division of Urology
- 熊小澐 Division of Radiology
- Shian-Shiang Wang Division of Urology
- 王樹吉 Division of Urology
- Jian-Ri Li Division of Urology
- Cheng-Kuang Yang Division of Urology
- 盧嘉文 Division of Urology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- 劉忠一 Division of Hematology & Oncology
- Kai-Jie Yu Division of Hematology & Oncology
- 張英勛 Division of Hematology & Oncology
- Yung-Chia Kao Division of Hematology & Oncology
- Wen-Cheng Chang Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Yeong-Shiau Pu Division of Urology
- CHING-CHU LU Division of Nuclear Medicine
- - - Division of Urology
- PO-MING CHOW Division of Urology
- YU-CHUAN LU Division of Urology
- YI-KAI CHANG Division of Urology
- - - Division of Urology
- YEN-HENG LIN Division of Radiology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Condition/Disease
Renal Cell Carcinoma Post Nephrectomy
Objectives
The purpose of this study is to evaluate the safety and efficacy of pembrolizumab (MK-3475) in the adjuvant treatment of adult participants who have undergone nephrectomy and have intermediate-high risk, high risk, or M1 no evidence of disease (M1 NED) renal cell carcinoma (RCC) with clear cell component.
The primary study hypothesis is that pembrolizumab is superior to placebo with respect to Disease-free Survival (DFS) as assessed by the Investigator in male and female participants with intermediate-high risk, high risk and M1 NED RCC.
Test Drug
Keytruda®
Active Ingredient
Pembrolizumab
Dosage Form
injection
Dosage
100mg
Endpoints
Primary Outcome Measures :
Disease-free Survival (DFS) as Assessed by the Investigator [ Time Frame: Up to approximately 50 months ]
DFS, as assessed by the investigator, is defined as the time from randomization to the first documented local recurrence, distant kidney cancer metastasis(es), or death due to any cause, whichever occurs first.
Secondary Outcome Measures :
Overall Survival (OS) [ Time Frame: Up to approximately 72 months ]
OS is defined as the time from randomization to death due to any cause.
Disease-free Survival (DFS) as Assessed by the Investigator [ Time Frame: Up to approximately 50 months ]
DFS, as assessed by the investigator, is defined as the time from randomization to the first documented local recurrence, distant kidney cancer metastasis(es), or death due to any cause, whichever occurs first.
Secondary Outcome Measures :
Overall Survival (OS) [ Time Frame: Up to approximately 72 months ]
OS is defined as the time from randomization to death due to any cause.
Inclution Criteria
Inclusion Criteria
Participants are eligible to be included in the study only if all of the following
criteria apply:
1. Must have histologically confirmed diagnosis of RCC with clear cell
component with or without sarcomatoid features. Diagnosis of RCC with
clear cell component is to be made by the investigator and does not require
central histology review.
2. Be ≥18 years of age on day of signing informed consent.
3. Female participants of childbearing potential must have a negative urine or
serum pregnancy test within 72 hours prior to randomization. If the urine
test is positive or cannot be confirmed as negative, a serum pregnancy test
will be required.
4. Female participants of childbearing potential must be willing to use an
adequate method of contraception as outlined in Appendix 5, for the course
of the trial through 120 days after the last dose of trial drug.
Note: Abstinence is acceptable if this is the usual lifestyle and preferred
contraception for the participant.
5. Male participants of childbearing potential must agree to use an adequate
method of contraception as outlined in Appendix 5, starting with the first
dose of trial therapy through 120 days after the last dose of trial therapy.
Note: Abstinence is acceptable if this is the usual lifestyle and preferred
contraception for the participant.
6. The participant provides written informed consent/assent for the trial. The
participant may also provide consent/assent for Future Biomedical Research; however the participant may participate in the main trial without
participating in Future Biomedical Research.
7. Have intermediate-high risk, high risk, or M1 NED RCC as defined by the
following pathological tumor-node-metastasis and Fuhrman grading status:
a) Intermediate-high risk RCC
pT2, Gr. 4 or sarcomatoid, N0, M0
pT3, Any Gr., N0, M0
b)High risk RCC
pT4, Any Gr. N0, M0
pT Any stage, Any Gr., N+, M0
c) M1 NED RCC (participants who present not only with the primary kidney
tumor but also solid, isolated, soft tissue metastases that can be completely
resected at the time of nephrectomy)
8. Have received no prior systemic therapy for advanced RCC (except
nephrectomy or metastasectomy).
9. Have undergone a partial nephroprotective or radical complete nephrectomy
(and complete resection of metastatic lesion(s) in M1 NED participants)
with negative surgical margins.
10. Must have undergone a nephrectomy (and metastasectomy for M1 NED)
≥28 days prior to signing informed consent and must be randomized ≤12
weeks after surgery.
11. Must be tumor-free as assessed by the Investigator and validated by either
CT or MRI scan of the brain and CAP and a bone scan ≤28 days from
randomization. All baseline scans must be sent to the central imaging
vendor and receipt must be confirmed prior to randomization.
12. Have provided adequate tissue from the primary tumor (and resected
metastatic lesion for M1 NED participants). Adequacy of the samples for
biomarker analysis will be evaluated by a central laboratory.
Note: If submitting unstained cut slides, newly cut slides should be
submitted to the testing laboratory within 14 days from the date the slides
are cut (details pertaining to tumor tissue submission and guidelines for
tissue adequacy can be found in the Procedure Manual).
13. Have an Eastern Cooperative Oncology Group Performance Status (ECOG
PS) of 0 or 1.
14. Have adequate organ function as defined in the following table. Specimens
must be collected within 10 days prior to randomization.
Participants are eligible to be included in the study only if all of the following
criteria apply:
1. Must have histologically confirmed diagnosis of RCC with clear cell
component with or without sarcomatoid features. Diagnosis of RCC with
clear cell component is to be made by the investigator and does not require
central histology review.
2. Be ≥18 years of age on day of signing informed consent.
3. Female participants of childbearing potential must have a negative urine or
serum pregnancy test within 72 hours prior to randomization. If the urine
test is positive or cannot be confirmed as negative, a serum pregnancy test
will be required.
4. Female participants of childbearing potential must be willing to use an
adequate method of contraception as outlined in Appendix 5, for the course
of the trial through 120 days after the last dose of trial drug.
Note: Abstinence is acceptable if this is the usual lifestyle and preferred
contraception for the participant.
5. Male participants of childbearing potential must agree to use an adequate
method of contraception as outlined in Appendix 5, starting with the first
dose of trial therapy through 120 days after the last dose of trial therapy.
Note: Abstinence is acceptable if this is the usual lifestyle and preferred
contraception for the participant.
6. The participant provides written informed consent/assent for the trial. The
participant may also provide consent/assent for Future Biomedical Research; however the participant may participate in the main trial without
participating in Future Biomedical Research.
7. Have intermediate-high risk, high risk, or M1 NED RCC as defined by the
following pathological tumor-node-metastasis and Fuhrman grading status:
a) Intermediate-high risk RCC
pT2, Gr. 4 or sarcomatoid, N0, M0
pT3, Any Gr., N0, M0
b)High risk RCC
pT4, Any Gr. N0, M0
pT Any stage, Any Gr., N+, M0
c) M1 NED RCC (participants who present not only with the primary kidney
tumor but also solid, isolated, soft tissue metastases that can be completely
resected at the time of nephrectomy)
8. Have received no prior systemic therapy for advanced RCC (except
nephrectomy or metastasectomy).
9. Have undergone a partial nephroprotective or radical complete nephrectomy
(and complete resection of metastatic lesion(s) in M1 NED participants)
with negative surgical margins.
10. Must have undergone a nephrectomy (and metastasectomy for M1 NED)
≥28 days prior to signing informed consent and must be randomized ≤12
weeks after surgery.
11. Must be tumor-free as assessed by the Investigator and validated by either
CT or MRI scan of the brain and CAP and a bone scan ≤28 days from
randomization. All baseline scans must be sent to the central imaging
vendor and receipt must be confirmed prior to randomization.
12. Have provided adequate tissue from the primary tumor (and resected
metastatic lesion for M1 NED participants). Adequacy of the samples for
biomarker analysis will be evaluated by a central laboratory.
Note: If submitting unstained cut slides, newly cut slides should be
submitted to the testing laboratory within 14 days from the date the slides
are cut (details pertaining to tumor tissue submission and guidelines for
tissue adequacy can be found in the Procedure Manual).
13. Have an Eastern Cooperative Oncology Group Performance Status (ECOG
PS) of 0 or 1.
14. Have adequate organ function as defined in the following table. Specimens
must be collected within 10 days prior to randomization.
Exclusion Criteria
Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
1. Has had major surgery, other than nephrectomy plus resection of
pre-existing metastases for M1 NED participants, within 12 weeks prior to
randomization.
Note: If participants received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention
prior to starting study treatment.
2. Has received prior radiotherapy for RCC.
3. Has residual thrombus post nephrectomy in the vena renalis or vena cava.
4. Has a diagnosis of immunodeficiency or is receiving chronic systemic
steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent)
or any other form of immunosuppressive therapy within 7 days prior the
first dose of study treatment.
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 known additional malignancy that is progressing or requires active
treatment. Exceptions include early-stage cancers (carcinoma in situ or
Stage 1) treated with curative intent, basal cell carcinoma of the skin,
squamous cell carcinoma of the skin, in situ cervical cancer, in situ prostate
cancer, or in situ breast cancer that has undergone potentially curative
therapy.
7. Has a history of (non-infectious) pneumonitis that required steroids or has
current pneumonitis.
8. Has an active infection requiring systemic therapy.
9. Has a known history of human immunodeficiency virus infection. No
human immunodeficiency virus testing is required unless mandated by local
health authority.
10. Has a known active hepatitis B (hepatitis B surface antigen reactive) or
hepatitis C virus (eg, hepatitis C virus [HCV] RNA [qualitative] is detected).
Note: HCV RNA testing is not required in those countries where local
standard of care uses only Hepatitis C antibody testing as evidence of status
of Hepatitis C.
11. Has a known history of active tuberculosis (Bacillus tuberculosis).
12. Has a history or current evidence of any condition, therapy, or laboratory
abnormality that might confound the results of the trial, interfere with the
participant’s participation for the full duration of the trial, or is not in the
best interest of the participant to participate, in the opinion of the treating
investigator.
13. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial in the opinion of the
investigator.
14. Has had a prior solid organ transplant.
15. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its
excipients (refer to Investigator’s Brochure for further details on excipients).
16. A woman of childbearing potential (WOCBP) who has a positive urine
pregnancy test within 72 hours before randomization. If the urine test is
positive or cannot be confirmed as negative, a serum pregnancy test will be
required. Participants must be excluded/discontinued from the trial in the
event of a positive or borderline positive test result.
17. Is pregnant or breastfeeding, or expecting to conceive or father children
within the projected duration of the trial, starting with the Screening visit
through 120 days after the last dose of study treatment.
18. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2
agent or with an agent directed to another co-inhibitory T-cell receptor (ie,
CTLA-4, OX-40, CD137) or has previously participated in a Merck
pembrolizumab (MK-3475) clinical trial.
19. Has received prior anticancer therapy, monoclonal antibody, chemotherapy,
or an investigational agent or device within 4 weeks or 5 half-lives
(whichever is longer) before first dose of study treatment or not recovered
(ie, must be ≤Grade 1 or at baseline) from AEs due to previously
administered agents.
Note: Upon consultation with the Sponsor, denosumab may be allowed for
bone protective purposes if dosing has been stable for ≥2 weeks before
screening.
Note: Participants with ≤Grade 2 neuropathy are an exception and may
qualify for the trial.
20. Has received a live vaccine within 30 days prior to the first dose of study
treatment. 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, 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.
21. Is currently participating in or has participated in a trial of an investigational
agent or has used an investigational device within 4 weeks prior to the first
dose of study treatment.
Note: Participants who have entered the follow-up phase of an investigational trial may participate as long as it has been 4 weeks or 5
half-lives after the last dose of the previous investigational agent.
Participants are excluded from the study if any of the following criteria apply:
1. Has had major surgery, other than nephrectomy plus resection of
pre-existing metastases for M1 NED participants, within 12 weeks prior to
randomization.
Note: If participants received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention
prior to starting study treatment.
2. Has received prior radiotherapy for RCC.
3. Has residual thrombus post nephrectomy in the vena renalis or vena cava.
4. Has a diagnosis of immunodeficiency or is receiving chronic systemic
steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent)
or any other form of immunosuppressive therapy within 7 days prior the
first dose of study treatment.
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 known additional malignancy that is progressing or requires active
treatment. Exceptions include early-stage cancers (carcinoma in situ or
Stage 1) treated with curative intent, basal cell carcinoma of the skin,
squamous cell carcinoma of the skin, in situ cervical cancer, in situ prostate
cancer, or in situ breast cancer that has undergone potentially curative
therapy.
7. Has a history of (non-infectious) pneumonitis that required steroids or has
current pneumonitis.
8. Has an active infection requiring systemic therapy.
9. Has a known history of human immunodeficiency virus infection. No
human immunodeficiency virus testing is required unless mandated by local
health authority.
10. Has a known active hepatitis B (hepatitis B surface antigen reactive) or
hepatitis C virus (eg, hepatitis C virus [HCV] RNA [qualitative] is detected).
Note: HCV RNA testing is not required in those countries where local
standard of care uses only Hepatitis C antibody testing as evidence of status
of Hepatitis C.
11. Has a known history of active tuberculosis (Bacillus tuberculosis).
12. Has a history or current evidence of any condition, therapy, or laboratory
abnormality that might confound the results of the trial, interfere with the
participant’s participation for the full duration of the trial, or is not in the
best interest of the participant to participate, in the opinion of the treating
investigator.
13. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial in the opinion of the
investigator.
14. Has had a prior solid organ transplant.
15. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its
excipients (refer to Investigator’s Brochure for further details on excipients).
16. A woman of childbearing potential (WOCBP) who has a positive urine
pregnancy test within 72 hours before randomization. If the urine test is
positive or cannot be confirmed as negative, a serum pregnancy test will be
required. Participants must be excluded/discontinued from the trial in the
event of a positive or borderline positive test result.
17. Is pregnant or breastfeeding, or expecting to conceive or father children
within the projected duration of the trial, starting with the Screening visit
through 120 days after the last dose of study treatment.
18. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2
agent or with an agent directed to another co-inhibitory T-cell receptor (ie,
CTLA-4, OX-40, CD137) or has previously participated in a Merck
pembrolizumab (MK-3475) clinical trial.
19. Has received prior anticancer therapy, monoclonal antibody, chemotherapy,
or an investigational agent or device within 4 weeks or 5 half-lives
(whichever is longer) before first dose of study treatment or not recovered
(ie, must be ≤Grade 1 or at baseline) from AEs due to previously
administered agents.
Note: Upon consultation with the Sponsor, denosumab may be allowed for
bone protective purposes if dosing has been stable for ≥2 weeks before
screening.
Note: Participants with ≤Grade 2 neuropathy are an exception and may
qualify for the trial.
20. Has received a live vaccine within 30 days prior to the first dose of study
treatment. 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, 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.
21. Is currently participating in or has participated in a trial of an investigational
agent or has used an investigational device within 4 weeks prior to the first
dose of study treatment.
Note: Participants who have entered the follow-up phase of an investigational trial may participate as long as it has been 4 weeks or 5
half-lives after the last dose of the previous investigational agent.
The Estimated Number of Participants
-
Taiwan
30 participants
-
Global
950 participants
