Clinical Trials List
Protocol NumberMK3475-590
NCT Number(ClinicalTrials.gov Identfier)NCT03189719
Completed
2017-06-01 - 2024-04-08
Phase III
Terminated9
ICD-10C16
Malignant neoplasm of stomach
ICD-10D00
Carcinoma in situ of oral cavity, esophagus and stomach
A Randomized, Double-Blind, Placebo-Controlled Phase III Clinical Trial of Pembrolizumab (MK-3475) in Combination With Cisplatin and 5-Fluorouracil Versus Placebo in Combination With Cisplatin and 5-Fluorouracil as First-Line Treatment in Subjects With Advanced/Metastatic Esophageal Carcinoma (KEYNOTE-590)
-
Trial Applicant
Merck Sharp & Dohme (I.A.) LLC
-
Sponsor
Merck Sharp & Dohme Corp.
-
Trial scale
Multi-Regional Multi-Center
-
Update
2026/02/01
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Chang-Fang Chiu Division of Hematology & Oncology
- Ming-Yu Lien Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Nai-Jung Chiang Division of Hematology & Oncology
- Chia-Jui Yen Division of Hematology & Oncology
- Yau-Lin Tseng Division of Thoracic Surgery
- Yi-Ting Yen Division of Thoracic Surgery
- 劉奕廷 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- Yao-Yu Hsieh Division of Hematology & Oncology
- Huey-En Tzeng Division of Hematology & Oncology
- Tsu-Yi Chao Division of Hematology & Oncology
- 蘇勇誠 Division of Hematology & Oncology
- Wei-Hong Cheng Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
2 Terminated
Audit
None
Co-Principal Investigator
- Chi-Ju Yeh Division of Others -
- Mengting Peng Division of Hematology & Oncology
- 陳煥武 Division of Radiology
- Chia-Hsun Hsieh Division of Hematology & Oncology
- Yung-Chia Kao Division of Hematology & Oncology
- 張鈞弼 Division of Radiology
- Chi-Ting Liau Division of Hematology & Oncology
- Yu-Chuan Chang Division of Nuclear Medicine
- Ming-Mo Hou Division of Hematology & Oncology
- Po-Jung Su Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Co-Principal Investigator
- TA-CHEN HUANG Division of Hematology & Oncology
- Kun-Huei Yeh Division of Hematology & Oncology
- JHE-CYUAN GUO Division of Hematology & Oncology
- Chia-Chi Lin Division of Hematology & Oncology
- Ann-Lii Cheng Division of Hematology & Oncology
- Wei-Wu Chen Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 柯萬盛 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
Advanced/Metastatic Esophageal Carcinoma
Objectives
The purpose of this trial is to evaluate efficacy and safety of pembrolizumab plus standard of care (SOC) chemotherapy with cisplatin and 5-fluorouracil (5-FU) versus placebo plus SOC chemotherapy with cisplatin and 5-FU as first-line treatment in participants with locally advanced or metastatic esophageal carcinoma.
Test Drug
Keytruda
Active Ingredient
Pembrolizumab
Dosage Form
Injection
Dosage
100 mg/ 4mL
Endpoints
Primary Efficacy Endpoints: OS(Overall survival )、PFS(Progression-free survival)
Secondary Efficacy Endpoints: Objective Response Rate (ORR) 、Duration of Response (DOR)、efficacy and safety evaluation、Life style quality
Secondary Efficacy Endpoints: Objective Response Rate (ORR) 、Duration of Response (DOR)、efficacy and safety evaluation、Life style quality
Inclution Criteria
Subject Inclusion Criteria
In order to be eligible for participation in this trial, the subject must:
1. Be willing and able to provide written informed consent for the trial. The
subject may also provide consent for Future Biomedical Research.
However, the subject may participate in the trial without participating in
Future Biomedical Research.
2. Be ≥ 18 years of age on the day of signing informed consent.
3. Have histologically or cytologically confirmed diagnosis of locally
advanced unresectable or metastatic adenocarcinoma or squamous cell
carcinoma of the esophagus or advanced/metastatic Siewert type 1
adenocarcinoma of the EGJ.
a. Subjects with direct invasion into adjacent organs such as the aorta or
trachea (T4b disease) should be closely evaluated for bleeding risk prior
to enrollment and a Sponsor consultation before enrollment is required.
b. Subjects with Siewert type 1 adenocarcinoma of the EGJ with known
human epidermal growth factor receptor-2/neu (HER 2/neu)-positive
tumors are not eligible. If HER-2/neu status is unknown, site should
follow local standards for HER-2/neu testing.
4. Have measurable disease per RECIST 1.1 as determined by the local site
investigator/radiology assessment. A lesion(s) situated in a previously
irradiated area can be considered a target lesion(s) if progression has been
demonstrated and the lesion(s) is considered measurable per RECIST 1.1
criteria.
Note: The same image acquisition and processing parameters should be used
throughout the study for a given subject.
5. Have an ECOG performance status of 0 to 1.
6. Provide either a newly obtained or archival tissue sample for intratumoral
immune related GEP analysis and PD-L1 by immunohistochemistry
analysis. Newly obtained tissue is preferred. Formalin-fixed,
paraffin-embedded (FFPE) block specimens are preferred to slides. Repeat
samples will be required if none of the samples submitted (archival or newly
obtained) is adequate. For purposes of this study, newly obtained tissue
refers to tissue that was collected between the last line of therapy and the
first dose of study medication.
a. Central laboratory confirmation of tumor tissue sample adequacy is
required prior to subject randomization in the study. If multiple tumor
samples are submitted, at least one of the samples must be confirmed to
be adequate by the central laboratory prior to subject being enrolled.
b. For subjects from whom newly obtained samples cannot be obtained
(e.g., inaccessible or subject safety concern), an archival specimen may be submitted.
c. If newly obtained tissue is provided and an archival tissue sample is
available, it should also be provided to support evaluation of the clinical
utility of immune-related GEP assessment and PD-L1 analysis by
immunohistochemistry in newly obtained vs. archival tissue samples.
However, a subject will not be excluded from participating in the study
if he/she has provided newly obtained tissue and an archival tissue
sample is not available or is otherwise insufficient for analysis.
7. Female subjects 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. If first dose is given > 72 hours post randomization,
pregnancy test should be repeated within 72 hours of first dose.
8. Female subjects of childbearing potential must be willing to use an adequate
method of contraception as outlined in Section 5.7.2 – Contraception, for the
course of the study through 120 days after the last dose of study therapy.
Note: Abstinence is acceptable if this is the usual lifestyle and preferred
contraception for the subject.
9. Male subjects of childbearing potential must agree to use an adequate
method of contraception as outlined in protocol Section 5.7.2 –
Contraception, starting with the first dose of study therapy through 120 days
after the last dose of study therapy and refrain from donating sperm during
this period.
Note: Abstinence is acceptable if this is the usual lifestyle and preferred
contraception for the subject.
10. Have adequate organ function as defined in Table 1. Specimens must be
collected within 14 days prior to the start of study treatment.
In order to be eligible for participation in this trial, the subject must:
1. Be willing and able to provide written informed consent for the trial. The
subject may also provide consent for Future Biomedical Research.
However, the subject may participate in the trial without participating in
Future Biomedical Research.
2. Be ≥ 18 years of age on the day of signing informed consent.
3. Have histologically or cytologically confirmed diagnosis of locally
advanced unresectable or metastatic adenocarcinoma or squamous cell
carcinoma of the esophagus or advanced/metastatic Siewert type 1
adenocarcinoma of the EGJ.
a. Subjects with direct invasion into adjacent organs such as the aorta or
trachea (T4b disease) should be closely evaluated for bleeding risk prior
to enrollment and a Sponsor consultation before enrollment is required.
b. Subjects with Siewert type 1 adenocarcinoma of the EGJ with known
human epidermal growth factor receptor-2/neu (HER 2/neu)-positive
tumors are not eligible. If HER-2/neu status is unknown, site should
follow local standards for HER-2/neu testing.
4. Have measurable disease per RECIST 1.1 as determined by the local site
investigator/radiology assessment. A lesion(s) situated in a previously
irradiated area can be considered a target lesion(s) if progression has been
demonstrated and the lesion(s) is considered measurable per RECIST 1.1
criteria.
Note: The same image acquisition and processing parameters should be used
throughout the study for a given subject.
5. Have an ECOG performance status of 0 to 1.
6. Provide either a newly obtained or archival tissue sample for intratumoral
immune related GEP analysis and PD-L1 by immunohistochemistry
analysis. Newly obtained tissue is preferred. Formalin-fixed,
paraffin-embedded (FFPE) block specimens are preferred to slides. Repeat
samples will be required if none of the samples submitted (archival or newly
obtained) is adequate. For purposes of this study, newly obtained tissue
refers to tissue that was collected between the last line of therapy and the
first dose of study medication.
a. Central laboratory confirmation of tumor tissue sample adequacy is
required prior to subject randomization in the study. If multiple tumor
samples are submitted, at least one of the samples must be confirmed to
be adequate by the central laboratory prior to subject being enrolled.
b. For subjects from whom newly obtained samples cannot be obtained
(e.g., inaccessible or subject safety concern), an archival specimen may be submitted.
c. If newly obtained tissue is provided and an archival tissue sample is
available, it should also be provided to support evaluation of the clinical
utility of immune-related GEP assessment and PD-L1 analysis by
immunohistochemistry in newly obtained vs. archival tissue samples.
However, a subject will not be excluded from participating in the study
if he/she has provided newly obtained tissue and an archival tissue
sample is not available or is otherwise insufficient for analysis.
7. Female subjects 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. If first dose is given > 72 hours post randomization,
pregnancy test should be repeated within 72 hours of first dose.
8. Female subjects of childbearing potential must be willing to use an adequate
method of contraception as outlined in Section 5.7.2 – Contraception, for the
course of the study through 120 days after the last dose of study therapy.
Note: Abstinence is acceptable if this is the usual lifestyle and preferred
contraception for the subject.
9. Male subjects of childbearing potential must agree to use an adequate
method of contraception as outlined in protocol Section 5.7.2 –
Contraception, starting with the first dose of study therapy through 120 days
after the last dose of study therapy and refrain from donating sperm during
this period.
Note: Abstinence is acceptable if this is the usual lifestyle and preferred
contraception for the subject.
10. Have adequate organ function as defined in Table 1. Specimens must be
collected within 14 days prior to the start of study treatment.
Exclusion Criteria
Subject Exclusion Criteria
The subject must be excluded from participating in the trial if the subject:
1. Has locally advanced esophageal carcinoma that is resectable or potentially
curable with radiation therapy (as determined by local investigator).
2. Has had previous therapy for advanced/metastatic adenocarcinoma or
squamous cell cancer of the esophagus or advanced/metastatic Siewert type
1 adenocarcinoma of the EGJ. Subjects may have received prior
neoadjuvant or adjuvant therapy as long as it was completed at least 6
months prior to randomization.
3. Has had major surgery, open biopsy, or significant traumatic injury within
28 days prior to randomization, or anticipation of the need for major surgery
during the course of study treatment.
4. 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, or in situ breast
cancer that has undergone potentially curative therapy.
5. Has known active central nervous system metastases and/or carcinomatous
meningitis. Subjects with previously treated brain metastases may
participate provided they are stable (without evidence of progression by
imaging for at least 4 weeks prior to the first dose of trial treatment and any
neurologic symptoms have returned to baseline), have no evidence of new
or enlarging brain metastases confirmed by repeat imaging, and have not
required steroids for at least 14 days before the first dose of trial treatment.
This exception does not include carcinomatous meningitis, which is
excluded regardless of clinical stability.
6. Has an active autoimmune disease that has required systemic treatment in
past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or
immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin,
or physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency) is not considered a form of systemic treatment and is allowed.
Brief (i.e., < 7 days) use of systemic corticosteroids is allowed when use is
considered standard of care by investigator.
7. 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 to the
first dose of trial treatment.
8. Has a history of (non-infectious) pneumonitis that required steroids or has
current pneumonitis.
9. Has an active infection requiring systemic therapy.
10. Has a history or current evidence of any condition (e.g., known deficiency
of the enzyme dihydropyrimidine dehydrogenase), 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.
11. Has known psychiatric or substance abuse disorders that would interfere
with cooperation with the requirements of the trial.
12. 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.
13. 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 (i.e.,
CTLA-4, OX-40, CD137) or has previously participated in a
pembrolizumab (MK-3475) clinical trial.
14. Has severe hypersensitivity (≥ Grade 3) to any study treatment
(pembrolizumab, cisplatin, or 5-FU) and/or any of its excipients.
15. Has a known history of active tuberculosis (Bacillus tuberculosis).
16. Has a known history of human immunodeficiency virus (HIV) infection.
No HIV testing is required unless mandated by local health authority.
17. Has known history of or is positive for hepatitis B (hepatitis B surface
antigen reactive) or hepatitis C (hepatitis C virus RNA or hepatitis C
antibody is detected). No hepatitis testing is required unless mandated by
local health authority.
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 the first dose of trial treatment.
Note: Subjects who have entered the follow-up phase of an investigational trial
may participate as long as it has been 4 weeks after the last dose of the
previous investigational agent.
19. Has received a live vaccine within 30 days prior to the first dose of trial
drug. 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 (e.g., FluMist®) are live
attenuated vaccines and are not allowed.
The subject must be excluded from participating in the trial if the subject:
1. Has locally advanced esophageal carcinoma that is resectable or potentially
curable with radiation therapy (as determined by local investigator).
2. Has had previous therapy for advanced/metastatic adenocarcinoma or
squamous cell cancer of the esophagus or advanced/metastatic Siewert type
1 adenocarcinoma of the EGJ. Subjects may have received prior
neoadjuvant or adjuvant therapy as long as it was completed at least 6
months prior to randomization.
3. Has had major surgery, open biopsy, or significant traumatic injury within
28 days prior to randomization, or anticipation of the need for major surgery
during the course of study treatment.
4. 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, or in situ breast
cancer that has undergone potentially curative therapy.
5. Has known active central nervous system metastases and/or carcinomatous
meningitis. Subjects with previously treated brain metastases may
participate provided they are stable (without evidence of progression by
imaging for at least 4 weeks prior to the first dose of trial treatment and any
neurologic symptoms have returned to baseline), have no evidence of new
or enlarging brain metastases confirmed by repeat imaging, and have not
required steroids for at least 14 days before the first dose of trial treatment.
This exception does not include carcinomatous meningitis, which is
excluded regardless of clinical stability.
6. Has an active autoimmune disease that has required systemic treatment in
past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or
immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin,
or physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency) is not considered a form of systemic treatment and is allowed.
Brief (i.e., < 7 days) use of systemic corticosteroids is allowed when use is
considered standard of care by investigator.
7. 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 to the
first dose of trial treatment.
8. Has a history of (non-infectious) pneumonitis that required steroids or has
current pneumonitis.
9. Has an active infection requiring systemic therapy.
10. Has a history or current evidence of any condition (e.g., known deficiency
of the enzyme dihydropyrimidine dehydrogenase), 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.
11. Has known psychiatric or substance abuse disorders that would interfere
with cooperation with the requirements of the trial.
12. 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.
13. 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 (i.e.,
CTLA-4, OX-40, CD137) or has previously participated in a
pembrolizumab (MK-3475) clinical trial.
14. Has severe hypersensitivity (≥ Grade 3) to any study treatment
(pembrolizumab, cisplatin, or 5-FU) and/or any of its excipients.
15. Has a known history of active tuberculosis (Bacillus tuberculosis).
16. Has a known history of human immunodeficiency virus (HIV) infection.
No HIV testing is required unless mandated by local health authority.
17. Has known history of or is positive for hepatitis B (hepatitis B surface
antigen reactive) or hepatitis C (hepatitis C virus RNA or hepatitis C
antibody is detected). No hepatitis testing is required unless mandated by
local health authority.
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 the first dose of trial treatment.
Note: Subjects who have entered the follow-up phase of an investigational trial
may participate as long as it has been 4 weeks after the last dose of the
previous investigational agent.
19. Has received a live vaccine within 30 days prior to the first dose of trial
drug. 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 (e.g., FluMist®) are live
attenuated vaccines and are not allowed.
The Estimated Number of Participants
-
Taiwan
60 participants
-
Global
749 participants
