Clinical Trials List
Protocol NumberMK-3475-A18/ENGOT-cx11/GOG-3047
NCT Number(ClinicalTrials.gov Identfier)NCT04221945
Active
2020-03-01 - 2027-12-31
Phase III
Recruiting3
ICD-10D05.00
Lobular carcinoma in situ of unspecified breast
ICD-10D05.01
Lobular carcinoma in situ of right breast
ICD-10D05.02
Lobular carcinoma in situ of left breast
ICD-10D05.10
Intraductal carcinoma in situ of unspecified breast
ICD-10D05.11
Intraductal carcinoma in situ of right breast
ICD-10D05.12
Intraductal carcinoma in situ of left breast
ICD-10D05.80
Other specified type of carcinoma in situ of unspecified breast
ICD-10D05.81
Other specified type of carcinoma in situ of right breast
ICD-10D05.82
Other specified type of carcinoma in situ of left breast
ICD-10D05.90
Unspecified type of carcinoma in situ of unspecified breast
ICD-10D05.91
Unspecified type of carcinoma in situ of right breast
ICD-10D05.92
Unspecified type of carcinoma in situ of left breast
ICD-9233.0
Carcinoma in situ of breast
A Randomized, Phase 3, Double-Blind Study of Chemoradiotherapy With or Without Pembrolizumab for the Treatment of High-risk, Locally Advanced Cervical Cancer (KEYNOTE-A18/ENGOT-cx11/GOG-3047)
-
Trial Applicant
Merck Sharp & Dohme (I.A.) LLC
-
Sponsor
Merck Sharp & Dohme LLC
-
Trial scale
Multi-Regional Multi-Center
-
Update
2026/02/01
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 童寶玲 Division of Obstetrics & Gynecology
- 施怡倫 Division of Others
- 戴依柔 Division of Obstetrics & Gynecology
- 陳祈安 Division of Obstetrics & Gynecology
- 陳宇立 Division of Obstetrics & Gynecology
- 許哲瑜 Division of Radiation Therapy
- 郭冠廷 Division of Others
- 陳宇立 Division of Obstetrics & Gynecology
- Wen-Fang Cheng Division of Obstetrics & Gynecology
- YING-CHENG CHIANG Division of Obstetrics & Gynecology
- 陳苓諭 Division of Radiation Therapy
- 施怡倫 Division of Radiology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Chyong-Huey Lai Division of Obstetrics & Gynecology
- Angel Chao Division of Obstetrics & Gynecology
- Chun-Chieh Wang Division of Radiation Therapy
- 周宏學 Division of Obstetrics & Gynecology
- Huei-Jean Huang Division of Obstetrics & Gynecology
- 黃彥綾 Division of Radiology
- Yun-Hsin Tang Division of Obstetrics & Gynecology
- 周宏學 Division of Obstetrics & Gynecology
- Cheng-Tao Lin Division of Obstetrics & Gynecology
- 黃意婷 Division of Radiation Therapy
- 黃寬仁 Division of Obstetrics & Gynecology
- 陳威君 Division of Obstetrics & Gynecology
- 江盈瑩 Division of Radiation Therapy
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Uterine Cervical Neoplasms
Objectives
‧To compare concurrent chemoradiotherapy plus pembrolizumab with concurrent chemoradiotherapy plus placebo with respect to progression-free survival per RECIST 1.1 as assessed by blinded independent central review or by histopathologic confirmation of suspected local disease progression (in the absence of radiographic disease progressionper RECIST 1.1)
‧To compare concurrent chemoradiotherapy plus pembrolizumab with concurrent chemoradiotherapy plus placebo with respect to overall survival
Test Drug
Pembrolizumab (MK-3475)Pembrolizumab (MK-3475)
Active Ingredient
Pembrolizumab (Humanized anti-PD-1 mAb)
Dosage Form
Injection
Dosage
100 mg/ 4 mL
Endpoints
Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by the Investigator
Overall Survival (OS) : OS is the time from randomization to death due to any cause.
Overall Survival (OS) : OS is the time from randomization to death due to any cause.
Inclution Criteria
A participant will be eligible for inclusion in the study if the participant:
Type of Participant and Disease Characteristics
1. Has high-risk LACC (a or b below):
a. FIGO 2014 Stage IB2-IIB (with node-positive disease) – must meet criteria below
for positive pelvic lymph node OR para-aortic lymph node involvement
Pelvic lymph node involvement as assessed by one of the following criteria:
o Histopathologic, biopsy-proven pelvic node involvement, or
o 2 or more positive pelvic nodes by MRI or CT (≥1.5 cm shortest
dimension), or
o 2 or more positive pelvic nodes by PET / CT with SUV ≥2.5
Para-aortic lymph node involvement as assessed by one of the following
criteria:
o Histopathologic, biopsy-proven para-aortic node involvement, or
o 1 or more positive para-aortic nodes by MRI or CT (≥1.5 cm shortest
dimension), or
o 1 or more positive para-aortic nodes by PET / CT with SUV ≥2.5
b. FIGO 2014 Stages III-IVA (either node-positive or node-negative disease)
Refer to Appendix 9 for further details of FIGO 2014 staging for cervical cancer.
2. Has histologically-confirmed squamous cell carcinoma, adenocarcinoma, or
adenosquamous carcinoma of the cervix.
3. Has not previously received any definitive surgical, radiation, or systemic therapy for
cervical cancer and is immunotherapy-naïve. Note: Previous surgical procedure for
localized cervical tumor is allowed.
4. Has an ECOG performance status of 0 or 1 within 7 days prior to the first dose of study
intervention.
Demographics
5. Is female, at least 18 years of age at the time of signing the informed consent.
Female Participants
Contraceptive use by women should be consistent with local regulations regarding the
methods of contraception for those participating in clinical studies.
6. A female participant is eligible to participate if she is not pregnant or breastfeeding, and
at least one of the following conditions applies:
Is not a WOCBP
OR
Is a WOCBP and using a contraceptive method that is highly effective (with a failure
rate of <1% per year), with low user dependency, or be abstinent from heterosexual
intercourse as their preferred and usual lifestyle (abstinent on a long term and
persistent basis), as described in Appendix 5 during the intervention period and for at
least 120 days after the last dose of pembrolizumab or placebo and 180 days
following the end of chemoradiotherapy. The investigator should evaluate the
potential for contraceptive method failure (ie, noncompliance, recently initiated) in
relationship to the first dose of study intervention.
A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as
required by local regulations) within 24 hours before the first dose of study
intervention.
If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum
pregnancy test is required. In such cases, the participant must be excluded from
participation if the serum pregnancy result is positive.
Additional requirements for pregnancy testing during and after study intervention are
located in Appendix 5.
The investigator is responsible for review of medical history, menstrual history, and
recent sexual activity to decrease the risk for inclusion of a woman with an early
undetected pregnancy.
Informed Consent
7. 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. Refer to Appendix 7 for country-specific
requirements.
Additional Categories
8. Has radiographically evaluable disease, either measurable or nonmeasurable per
RECIST 1.1, as assessed by the local site investigator/radiology.
9. Has provided a tissue sample from a core or excisional biopsy of a tumor lesion for
confirmation of adequacy by the central vendor prior to randomization. Formalin-fixed,
paraffin embedded tissue blocks are preferred to slides (details pertaining to tumor tissue
submission can be found in the Procedures Manual).
10. Has adequate organ function as defined in the following table (Table 2). Specimens must
be collected within 7 days prior to the start of study intervention.
Type of Participant and Disease Characteristics
1. Has high-risk LACC (a or b below):
a. FIGO 2014 Stage IB2-IIB (with node-positive disease) – must meet criteria below
for positive pelvic lymph node OR para-aortic lymph node involvement
Pelvic lymph node involvement as assessed by one of the following criteria:
o Histopathologic, biopsy-proven pelvic node involvement, or
o 2 or more positive pelvic nodes by MRI or CT (≥1.5 cm shortest
dimension), or
o 2 or more positive pelvic nodes by PET / CT with SUV ≥2.5
Para-aortic lymph node involvement as assessed by one of the following
criteria:
o Histopathologic, biopsy-proven para-aortic node involvement, or
o 1 or more positive para-aortic nodes by MRI or CT (≥1.5 cm shortest
dimension), or
o 1 or more positive para-aortic nodes by PET / CT with SUV ≥2.5
b. FIGO 2014 Stages III-IVA (either node-positive or node-negative disease)
Refer to Appendix 9 for further details of FIGO 2014 staging for cervical cancer.
2. Has histologically-confirmed squamous cell carcinoma, adenocarcinoma, or
adenosquamous carcinoma of the cervix.
3. Has not previously received any definitive surgical, radiation, or systemic therapy for
cervical cancer and is immunotherapy-naïve. Note: Previous surgical procedure for
localized cervical tumor is allowed.
4. Has an ECOG performance status of 0 or 1 within 7 days prior to the first dose of study
intervention.
Demographics
5. Is female, at least 18 years of age at the time of signing the informed consent.
Female Participants
Contraceptive use by women should be consistent with local regulations regarding the
methods of contraception for those participating in clinical studies.
6. A female participant is eligible to participate if she is not pregnant or breastfeeding, and
at least one of the following conditions applies:
Is not a WOCBP
OR
Is a WOCBP and using a contraceptive method that is highly effective (with a failure
rate of <1% per year), with low user dependency, or be abstinent from heterosexual
intercourse as their preferred and usual lifestyle (abstinent on a long term and
persistent basis), as described in Appendix 5 during the intervention period and for at
least 120 days after the last dose of pembrolizumab or placebo and 180 days
following the end of chemoradiotherapy. The investigator should evaluate the
potential for contraceptive method failure (ie, noncompliance, recently initiated) in
relationship to the first dose of study intervention.
A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as
required by local regulations) within 24 hours before the first dose of study
intervention.
If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum
pregnancy test is required. In such cases, the participant must be excluded from
participation if the serum pregnancy result is positive.
Additional requirements for pregnancy testing during and after study intervention are
located in Appendix 5.
The investigator is responsible for review of medical history, menstrual history, and
recent sexual activity to decrease the risk for inclusion of a woman with an early
undetected pregnancy.
Informed Consent
7. 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. Refer to Appendix 7 for country-specific
requirements.
Additional Categories
8. Has radiographically evaluable disease, either measurable or nonmeasurable per
RECIST 1.1, as assessed by the local site investigator/radiology.
9. Has provided a tissue sample from a core or excisional biopsy of a tumor lesion for
confirmation of adequacy by the central vendor prior to randomization. Formalin-fixed,
paraffin embedded tissue blocks are preferred to slides (details pertaining to tumor tissue
submission can be found in the Procedures Manual).
10. Has adequate organ function as defined in the following table (Table 2). Specimens must
be collected within 7 days prior to the start of study intervention.
Exclusion Criteria
The participant must be excluded from the study if the participant:
Medical Conditions
1. Has histological subtypes other than those allowed per inclusion criterion 2 (eg, sarcoma,
small cell carcinoma with neuroendocrine differentiation, non-epithelial cancer).
2. Has FIGO 2014 Stage IVB disease.
3. Has undergone a previous hysterectomy defined as removal of the entire uterus or will
have a hysterectomy as part of their initial cervical cancer therapy. NOTE: Women who
have had a partial/subtotal hysterectomy for reasons other than cervical cancer are
eligible to participate in the study.
4. Has bilateral hydronephrosis, unless at least one side has been stented or resolved by
positioning of nephrostomy.
5. Has anatomy or tumor geometry or any other reason or contraindication that cannot be
treated with intracavitary brachytherapy or a combination of intracavitary and interstitial
brachytherapy.
Prior/Concomitant Therapy
6. Has received a live vaccine within 30 days prior to the first dose of study intervention.
Examples of live vaccines include, but are not limited to, the following: measles, mumps,
rubella, varicella/zoster (chicken pox), yellow fever, rabies, 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.
7. Has received treatment with systemic immunostimulatory agents such as bacterial or viral
vaccines, colony stimulating factors, interferons, interleukins and vaccine combinations
within 6 weeks or 5 half-lives of the drug, whichever is shorter, prior to Cycle 1, Day 1.
Prior/Concurrent Clinical Study Experience
8. 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).
9. Has received prior systemic anticancer therapy including investigational agents within
4 weeks prior to randomization.
10. 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.
Diagnostic Assessments
11. Has any contraindication to the use of cisplatin.
12. 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 medication.
13. 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, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have
undergone potentially curative therapy are not excluded.
14. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
15. 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.
16. Has a history of (non-infectious) pneumonitis that required steroids or has current
pneumonitis.
17. Has an active infection requiring systemic therapy.
18. Has a known history of HIV infection.
Note: No testing for HIV is required unless mandated by local health authority. Refer to
Appendix 7 for country-specific requirements.
19. Has a known history of Hepatitis B (defined as 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. Refer to Appendix 7 for country-specific requirements.
20. Has a known history of active tuberculosis (TB; Bacillus tuberculosis).
21. Has a history or current evidence of any condition, therapy, lab abnormality, or other
circumstance that may increase the risk associated with study participation or study
intervention administration or may interfere with the interpretation of study results, and
in the judgment of the investigator or Sponsor, would make the participant inappropriate
for entry into this study.
22. Has a known psychiatric or substance abuse disorder that would interfere with the
participant’s ability to cooperate with the requirements of the study.
Other Exclusions
23. Is pregnant or breastfeeding or expecting to conceive children within the projected
duration of the study, starting with the screening visit through 120 days after the last dose
of pembrolizumab or placebo and 180 days following the end of chemoradiotherapy.
24. Has had an allogenic tissue/solid organ transplant.
Medical Conditions
1. Has histological subtypes other than those allowed per inclusion criterion 2 (eg, sarcoma,
small cell carcinoma with neuroendocrine differentiation, non-epithelial cancer).
2. Has FIGO 2014 Stage IVB disease.
3. Has undergone a previous hysterectomy defined as removal of the entire uterus or will
have a hysterectomy as part of their initial cervical cancer therapy. NOTE: Women who
have had a partial/subtotal hysterectomy for reasons other than cervical cancer are
eligible to participate in the study.
4. Has bilateral hydronephrosis, unless at least one side has been stented or resolved by
positioning of nephrostomy.
5. Has anatomy or tumor geometry or any other reason or contraindication that cannot be
treated with intracavitary brachytherapy or a combination of intracavitary and interstitial
brachytherapy.
Prior/Concomitant Therapy
6. Has received a live vaccine within 30 days prior to the first dose of study intervention.
Examples of live vaccines include, but are not limited to, the following: measles, mumps,
rubella, varicella/zoster (chicken pox), yellow fever, rabies, 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.
7. Has received treatment with systemic immunostimulatory agents such as bacterial or viral
vaccines, colony stimulating factors, interferons, interleukins and vaccine combinations
within 6 weeks or 5 half-lives of the drug, whichever is shorter, prior to Cycle 1, Day 1.
Prior/Concurrent Clinical Study Experience
8. 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).
9. Has received prior systemic anticancer therapy including investigational agents within
4 weeks prior to randomization.
10. 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.
Diagnostic Assessments
11. Has any contraindication to the use of cisplatin.
12. 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 medication.
13. 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, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have
undergone potentially curative therapy are not excluded.
14. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
15. 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.
16. Has a history of (non-infectious) pneumonitis that required steroids or has current
pneumonitis.
17. Has an active infection requiring systemic therapy.
18. Has a known history of HIV infection.
Note: No testing for HIV is required unless mandated by local health authority. Refer to
Appendix 7 for country-specific requirements.
19. Has a known history of Hepatitis B (defined as 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. Refer to Appendix 7 for country-specific requirements.
20. Has a known history of active tuberculosis (TB; Bacillus tuberculosis).
21. Has a history or current evidence of any condition, therapy, lab abnormality, or other
circumstance that may increase the risk associated with study participation or study
intervention administration or may interfere with the interpretation of study results, and
in the judgment of the investigator or Sponsor, would make the participant inappropriate
for entry into this study.
22. Has a known psychiatric or substance abuse disorder that would interfere with the
participant’s ability to cooperate with the requirements of the study.
Other Exclusions
23. Is pregnant or breastfeeding or expecting to conceive children within the projected
duration of the study, starting with the screening visit through 120 days after the last dose
of pembrolizumab or placebo and 180 days following the end of chemoradiotherapy.
24. Has had an allogenic tissue/solid organ transplant.
The Estimated Number of Participants
-
Taiwan
17 participants
-
Global
980 participants
