Clinical Trials List
Protocol NumberMK3475-119
NCT Number(ClinicalTrials.gov Identfier)NCT02555657
2015-10-01 - 2019-12-31
Phase III
Terminated4
ICD-10C50
Malignant neoplasm of breast
A Randomized Open-Label Phase III Study of Single Agent Pembrolizumab versus Single Agent Chemotherapy per Physician’s Choice for Metastatic Triple Negative Breast Cancer (mTNBC) – (KEYNOTE 119)
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Trial Applicant
Merck Sharp & Dohme (I.A.) LLC
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Sponsor
Merck Sharp & Dohme Corp.
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Liang-Chih Liu Division of General Surgery
- Chih-Jung Chen Division of General Surgery
- Tzu-Ting Chen Division of Hematology & Oncology
- Ching-Chan Lin Division of Hematology & Oncology
- HWEI-CHUNG WANG Division of General Surgery
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Wei-Pang Chung Division of Hematology & Oncology
- Yu-Min Yeh Division of Hematology & Oncology
- Shang-Yin Wu Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- Wen-Chi Shen Division of Hematology & Oncology
- Chan-Keng Yang Division of Hematology & Oncology
- Chi-Chang Yu Division of General Surgery
- Mengting Peng Division of Hematology & Oncology
- 張献崑 Division of Hematology & Oncology
- 周旭桓 Division of General Surgery
- 沈士哲 Division of General Surgery
- Yung-Chang Lin Division of Hematology & Oncology
- Hsien-Kun Chang Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
6 Terminated
Audit
CRO
Co-Principal Investigator
- 張端瑩 Division of Hematology & Oncology
- Ann-Lii Cheng Division of Hematology & Oncology
- Wei-Wu Chen Division of Hematology & Oncology
- 林季宏 Division of Hematology & Oncology
- JHE-CYUAN GUO Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Condition/Disease
Metastatic Triple Negative Breast Cancer (mTNBC)
Objectives
Primary Objective(s) & Hypothesis(es)
Pembrolizumab will be compared to TPC as 2L or 3L monotherapy in subjects with
centrally confirmed mTNBC:
1. Objective: To compare progression-free survival (PFS) based on RECIST 1.1
as assessed by blinded central imaging vendor in subjects with PD-L1 positive
tumors.
2. Objective: To compare PFS based on RECIST 1.1 as assessed by blinded
central imaging vendor in all subjects
3. Objective: To compare overall survival (OS) in subjects with PD-L1 positive
tumors.
4. Objective: To compare OS in all subjects.
Test Drug
Pembrolizumab (MK-3475)
Active Ingredient
Pembrolizumab
Dosage Form
Injection
Dosage
100 mg/ 4 mL/ vial
Endpoints
Primary Outcome Measures :
1. Overall Survival in Participants With Programmed Cell Death Ligand 1 (PD-L1) With Combined Positive Score (CPS) ≥10 [ Time Frame: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019) ]
Overall survival (OS) was defined as the time from randomization to death due to any cause.
2. Overall Survival in Participants With PD-L1 CPS ≥1 [ Time Frame: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019) ]
Overall survival (OS) was defined as the time from randomization to death due to any cause.
3. Overall Survival in All Participants [ Time Frame: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019) ]
Overall survival (OS) was defined as the time from randomization to death due to any cause.
1. Overall Survival in Participants With Programmed Cell Death Ligand 1 (PD-L1) With Combined Positive Score (CPS) ≥10 [ Time Frame: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019) ]
Overall survival (OS) was defined as the time from randomization to death due to any cause.
2. Overall Survival in Participants With PD-L1 CPS ≥1 [ Time Frame: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019) ]
Overall survival (OS) was defined as the time from randomization to death due to any cause.
3. Overall Survival in All Participants [ Time Frame: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019) ]
Overall survival (OS) was defined as the time from randomization to death due to any cause.
Inclution Criteria
In order to be eligible for participation in this trial, the subject must:
1. Have signed informed consent.
2. Be 18 years of age on day of signing informed consent.
3. Have received either one or two prior systemic treatments for metastatic breast cancer
and have documented disease progression on the most recent therapy.
4. Have been previously treated with an anthracycline and/or taxane in the (neo)adjuvant or
metastatic setting.
5. Have centrally confirmed mTNBC (determined by a newly obtained core or excisional
biopsy from a metastatic, not previously irradiated, tumor lesion).
6. Have measurable disease based on RECIST 1.1 as assessed by site investigator and local
radiology review.
7. Have provided a newly obtained core or excisional biopsy from a metastatic, not
previously irradiated, tumor lesion for central determination of triple-negative breast
cancer status and PD-L1 biomarker analysis. Adequacy of the biopsy specimen for the
above analyses must be confirmed by the central laboratory. Repeat samples may be
required if adequate tumor tissue is not provided.
Note: Subjects for whom fresh tumor biopsies cannot be obtained (e.g. inaccessible
tumor site or concern for subject safety) may submit an archived tumor specimen
only upon agreement from the Sponsor.
8. Have an ECOG performance status of 0 or 1 assessed within 10 days prior of treatment
initiation.
9. Demonstrate adequate organ function as defined in Table 2.
10. Female subjects of childbearing potential must have a negative serum pregnancy test
within 72 hours prior to randomization and agree to use effective contraception, as
defined in Section 5.7.2. Male subjects should agree to use an adequate method of
contraception starting at randomization through at least 120 days after the last dose of
pembrolizumab or TPC, according to local standard of care.
Note: For UK subjects, abstinence is acceptable if this is the established and preferred
contraception for the subject
1. Have signed informed consent.
2. Be 18 years of age on day of signing informed consent.
3. Have received either one or two prior systemic treatments for metastatic breast cancer
and have documented disease progression on the most recent therapy.
4. Have been previously treated with an anthracycline and/or taxane in the (neo)adjuvant or
metastatic setting.
5. Have centrally confirmed mTNBC (determined by a newly obtained core or excisional
biopsy from a metastatic, not previously irradiated, tumor lesion).
6. Have measurable disease based on RECIST 1.1 as assessed by site investigator and local
radiology review.
7. Have provided a newly obtained core or excisional biopsy from a metastatic, not
previously irradiated, tumor lesion for central determination of triple-negative breast
cancer status and PD-L1 biomarker analysis. Adequacy of the biopsy specimen for the
above analyses must be confirmed by the central laboratory. Repeat samples may be
required if adequate tumor tissue is not provided.
Note: Subjects for whom fresh tumor biopsies cannot be obtained (e.g. inaccessible
tumor site or concern for subject safety) may submit an archived tumor specimen
only upon agreement from the Sponsor.
8. Have an ECOG performance status of 0 or 1 assessed within 10 days prior of treatment
initiation.
9. Demonstrate adequate organ function as defined in Table 2.
10. Female subjects of childbearing potential must have a negative serum pregnancy test
within 72 hours prior to randomization and agree to use effective contraception, as
defined in Section 5.7.2. Male subjects should agree to use an adequate method of
contraception starting at randomization through at least 120 days after the last dose of
pembrolizumab or TPC, according to local standard of care.
Note: For UK subjects, abstinence is acceptable if this is the established and preferred
contraception for the subject
Exclusion Criteria
The subject must be excluded from participating in the trial if the subject:
1. Has participated in a study of an investigational agent/device and has received/is
receiving the investigational agent/device within 4 weeks of randomization.
Note: Subjects who have entered the follow-up phase of an investigational study may
participate as long as 4 weeks have elapsed since the last dose of the investigational
agent and/or removal of the device.
2. Has had monoclonal antibody (mAb) for direct anti-neoplastic treatment within 4 weeks
of randomization
3. Has had chemotherapy, targeted small molecule therapy, or radiation therapy within at
least 2 weeks of randomization
4. Has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously
administered therapy.
Note: Subjects with ≤ Grade 2 neuropathy or alopecia of any grade are an exception
to this criterion and may qualify for the study.
Note: If subject received major surgery, they must have recovered adequately from
the toxicity and/or complications from the surgery prior to randomization.
5. Has an active autoimmune disease that has required systemic treatment in the past 2 years
(i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
Note: Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
form of systemic treatment.
6. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
other form of immunosuppressive therapy within 7 days of randomization.
7. Has a known additional malignancy that progressed or required active treatment within
the last 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell
carcinoma of the skin that has undergone potentially curative therapy, and in situ cervical
cancer.
8. Has known active brain metastases and/or carcinomatous meningitis.
Note: Known brain metastases are considered active, if any of the following criteria
is 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
b. Neurological symptoms attributed to brain metastases have not returned to
baseline
c. Steroids were used for brain metastases within 28 days of randomization
9. Has active/history of pneumonitis requiring treatment with steroids or active/history of
interstitial lung disease.
10. Has an active infection requiring systemic therapy.
11. Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the trial, interfere with the subject’s participation for
the full duration of the trial, or is not in the best interest of the subject to participate, in
the opinion of the treating investigator.
12. Has known psychiatric or substance abuse disorders that would interfere with cooperation
with the requirements of the trial.
13. 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 trial treatment.
14. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 agent or with an
agent directed to another co-inhibitory T-cell receptor (e.g. CTLA-4, OX-40, CD137) or
has previously participated in Merck MK-3475 clinical trials.
15. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
16. Has a known history of Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV
RNA [qualitative] is detected).
17. Has received a live vaccine within 30 days of randomization.
18. Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or
child) who is investigational site or sponsor staff directly involved with this trial, unless
prospective IRB approval (by chair or designee) is given allowing exception to this
criterion for a specific subject.
1. Has participated in a study of an investigational agent/device and has received/is
receiving the investigational agent/device within 4 weeks of randomization.
Note: Subjects who have entered the follow-up phase of an investigational study may
participate as long as 4 weeks have elapsed since the last dose of the investigational
agent and/or removal of the device.
2. Has had monoclonal antibody (mAb) for direct anti-neoplastic treatment within 4 weeks
of randomization
3. Has had chemotherapy, targeted small molecule therapy, or radiation therapy within at
least 2 weeks of randomization
4. Has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously
administered therapy.
Note: Subjects with ≤ Grade 2 neuropathy or alopecia of any grade are an exception
to this criterion and may qualify for the study.
Note: If subject received major surgery, they must have recovered adequately from
the toxicity and/or complications from the surgery prior to randomization.
5. Has an active autoimmune disease that has required systemic treatment in the past 2 years
(i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
Note: Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
form of systemic treatment.
6. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
other form of immunosuppressive therapy within 7 days of randomization.
7. Has a known additional malignancy that progressed or required active treatment within
the last 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell
carcinoma of the skin that has undergone potentially curative therapy, and in situ cervical
cancer.
8. Has known active brain metastases and/or carcinomatous meningitis.
Note: Known brain metastases are considered active, if any of the following criteria
is 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
b. Neurological symptoms attributed to brain metastases have not returned to
baseline
c. Steroids were used for brain metastases within 28 days of randomization
9. Has active/history of pneumonitis requiring treatment with steroids or active/history of
interstitial lung disease.
10. Has an active infection requiring systemic therapy.
11. Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the trial, interfere with the subject’s participation for
the full duration of the trial, or is not in the best interest of the subject to participate, in
the opinion of the treating investigator.
12. Has known psychiatric or substance abuse disorders that would interfere with cooperation
with the requirements of the trial.
13. 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 trial treatment.
14. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 agent or with an
agent directed to another co-inhibitory T-cell receptor (e.g. CTLA-4, OX-40, CD137) or
has previously participated in Merck MK-3475 clinical trials.
15. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
16. Has a known history of Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV
RNA [qualitative] is detected).
17. Has received a live vaccine within 30 days of randomization.
18. Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or
child) who is investigational site or sponsor staff directly involved with this trial, unless
prospective IRB approval (by chair or designee) is given allowing exception to this
criterion for a specific subject.
The Estimated Number of Participants
-
Taiwan
30 participants
-
Global
750 participants
