Clinical Trials List
Protocol NumberMK3475-826
NCT Number(ClinicalTrials.gov Identfier)NCT03635567
Completed
2018-09-01 - 2024-12-19
Phase III
Recruiting1
Terminated5
ICD-10C53
Malignant neoplasm of cervix uteri
A Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial of Pembrolizumab (MK-3475) Plus Chemotherapy Versus Chemotherapy Plus Placebo for the First-Line Treatment of Persistent, Recurrent, or Metastatic Cervical Cancer (KEYNOTE-826)
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Trial Applicant
Merck Sharp & Dohme (I.A.) LLC
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Sponsor
Merck Sharp & Dohme LLC
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Trial scale
Multi-Regional Multi-Center
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Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- 沈書慧 Division of Radiology
- 劉顯慈 Division of Radiology
- Huann-Cheng Horng Division of Obstetrics & Gynecology
- Yen-Hou Chang Division of Obstetrics & Gynecology
- Yi-Jen Chen Division of Obstetrics & Gynecology
- 溫國璋 Division of Obstetrics & Gynecology
- Chi-Mu Chuang Division of Obstetrics & Gynecology
The Actual Total Number of Participants Enrolled
2 Terminated
Audit
None
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 陳鵬宇 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 周宏學 Division of Obstetrics & Gynecology
- Ting-Chang Chang Division of Obstetrics & Gynecology
- 黃寬仁 Division of Obstetrics & Gynecology
- 邱健泰 Division of Obstetrics & Gynecology
- 陳威君 Division of Obstetrics & Gynecology
- 周宏學 Division of Obstetrics & Gynecology
- Huei-Jean Huang Division of Obstetrics & Gynecology
- Gigin Lin Division of Radiology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Wei-Chun Chang Division of Obstetrics & Gynecology
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Persistent, Recurrent, or Metastatic Cervical Cancer
Objectives
Primary Outcome:
To compare progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as assessed by blinded independent central review (BICR)
To compare overall survival (OS)
Secondary Outcome:
To evaluate the objective response rate (ORR), duration of response (DOR), and 12-month PFS rate per RECIST 1.1 as assessed by BICR
To compare the safety and tolerability by the proportion of adverse events (AEs)
To evaluate changes in HealthRelated Quality of Life (HRQoL) assessments using the global score of the European Organisation for the Research and Treatment of Cancer (EORTC) QLQ-C30
Test Drug
Pembrolizumab (MK-3475)
Active Ingredient
Pembrolizumab (Humanized anti-PD-1 mAb)
Dosage Form
Injection
Dosage
100 mg/ 4 mL
Endpoints
Primary 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
Secondary Endpoints
- Objective Response (OR): Participants who have a best overall response of either confirmed complete response (CR) or partial response (PR)
- DOR: The time from the first documented evidence of CR or PR until the first documented disease progression or death due to any cause, whichever occurs first
- PFS: The time from randomization to the first documented disease progression or death due to any cause, whichever occurs first
- Participants experiencing adverse events (AEs), serious AEs, and immune-related AEs
- The EORTC QLQ-C30 global score
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
Secondary Endpoints
- Objective Response (OR): Participants who have a best overall response of either confirmed complete response (CR) or partial response (PR)
- DOR: The time from the first documented evidence of CR or PR until the first documented disease progression or death due to any cause, whichever occurs first
- PFS: The time from randomization to the first documented disease progression or death due to any cause, whichever occurs first
- Participants experiencing adverse events (AEs), serious AEs, and immune-related AEs
- The EORTC QLQ-C30 global score
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
Demographics
Female Participants
3. Not be pregnant (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 Appendix 5 or
b. A WOCBP must agree to follow the contraceptive guidance in 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 (Table 3)
within 14 days prior to randomization
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
Demographics
Female Participants
3. Not be pregnant (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 Appendix 5 or
b. A WOCBP must agree to follow the contraceptive guidance in 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 (Table 3)
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 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 has current
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 for use.
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 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 has current
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 for use.
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
30 participants
-
Global
600 participants
