Clinical Trials List
Protocol NumberMK3475-177
NCT Number(ClinicalTrials.gov Identfier)NCT02563002
2015-12-14 - 2020-10-31
Phase III
Terminated5
ICD-10C18
Malignant neoplasm of colon
A Phase III Study of Pembrolizumab (MK-3475) vs. Chemotherapy in Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Stage IV Colorectal Carcinoma (KEYNOTE-177)
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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
- Wu-Chou Su Division of Hematology & Oncology
- 陳柏全 Division of Hematology & Oncology
- Po-Wen Lin Division of Colorectal Surgery
- Shang-Yin Wu Division of Hematology & Oncology
- 林邵潔 Division of General Surgery
- Peng-Chan Lin Division of Hematology & Oncology
- Wen-Pin Su Division of Hematology & Oncology
- Jui-Hung Tsai Division of Hematology & Oncology
- Wei-Pang Chung Division of Hematology & Oncology
- Chia-Jui Yen Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Co-Principal Investigator
- 胡萬祥 Division of Colorectal Surgery
- 李克釗 Division of Colorectal Surgery
- Yu-Li Su Division of Hematology & Oncology
- 張家駱 Division of Colorectal Surgery
- Tai-Jan Chiu Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Wen-Chi Chou Division of Hematology & Oncology
- Ming-Mo Hou Division of Hematology & Oncology
- Jen-Shi Chen Division of Hematology & Oncology
- Mengting Peng Division of Hematology & Oncology
- Hung-Chih Hsu Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
3 Terminated
Audit
None
Co-Principal Investigator
- Ann-Lii Cheng Division of Hematology & Oncology
- 林育麟 Division of Hematology & Oncology
- YU-YUN SHAO Division of Hematology & Oncology
- Wei-Wu Chen Division of Hematology & Oncology
- Chiun Hsu Division of Hematology & Oncology
- Ying-Chun Shen Division of Hematology & Oncology
- 呂理駿 Division of Hematology & Oncology
- JHE-CYUAN GUO Division of Hematology & Oncology
- Chih-Hung Hsu Division of Hematology & Oncology
- 張端瑩 Division of Hematology & Oncology
- Hsiang-Fong Kao Division of Hematology & Oncology
- 林宗哲 Division of Hematology & Oncology
- TA-CHEN HUANG Division of Hematology & Oncology
- 陳國興 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Condition/Disease
Colorectal Carcinoma
Objectives
1. Primary Objective(s) & Hypothesis(es)
In subjects with first line (1L) stage IV MSI-H or dMMR CRC treated with
pembrolizumab (MK-3475) versus SOC chemotherapies,
Objective: To compare Progression Free Survival (PFS) per RECIST 1.1 by central
imaging vendor.
Hypothesis (H1): Pembrolizumab (MK-3475) prolongs PFS per RECIST 1.1 by
central imaging vendor compared to SOC chemotherapies.
2. Secondary Objective(s) & Hypothesis(es)
In subjects with 1L stage IV MSI-H or dMMR CRC treated with pembrolizumab
(MK-3475) versus SOC chemotherapies,
1) Objective: To compare Overall Response Rate (ORR) per RECIST 1.1 by
central imaging vendor.
Hypothesis (H2): Pembrolizumab (MK-3475) improves ORR compared to
SOC chemotherapies
2) Objective: To compare Overall Survival (OS).
Hypothesis (H3): Pembrolizumab (MK-3475) prolongs OS compared to SOC
chemotherapies.
3) Objective: To evaluate the safety and tolerability profiles.
Test Drug
Pembrolizumab (MK-3475)
Active Ingredient
Humanized anti-PD-1 mAb
Dosage Form
Intravenous Injection
Dosage
100 mg/4 mL/vial
Endpoints
Primary Outcome Measures :
1. Progression-free Survival (PFS) [ Time Frame: Up to 24 months ]
2. Overall Survival (OS) [ Time Frame: Up to 36 months ]
Secondary Outcome Measures :
1. Overall Response Rate (ORR) [ Time Frame: Up to 36 months ]
1. Progression-free Survival (PFS) [ Time Frame: Up to 24 months ]
2. Overall Survival (OS) [ Time Frame: Up to 36 months ]
Secondary Outcome Measures :
1. Overall Response Rate (ORR) [ Time Frame: Up to 36 months ]
Inclution Criteria
Diagnosis/Condition for Entry into the Trial
Male/Female subjects with Microsatellite Instability-High (MSI-H) or Mismatch
Repair Deficient (dMMR) Colorectal Cancer will be enrolled in this trial.
Subject Inclusion Criteria
In order to be eligible for participation in this trial, the subject must:
1. Provide written informed consent for the trial.
Be male or female who is ≥ 18 years of age on the date of signing informed
consent. (Subjects in Taiwan aged at least 20 years)
2. Have locally confirmed MMR deficient (dMMR) or microsatellite instability
high (MSI-H) stage IV colorectal carcinoma
3. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0
or 1
4. Have life expectancy of at least 3 months
5. Have measurable disease at baseline based on RECIST 1.1 as determined by the
local site Investigator/radiology assessment.
6. Female subjects of childbearing potential must have a negative serum pregnancy
test within 72 hours prior to receiving the first dose of study medication.
7. Female subjects of childbearing potential must be willing to use an adequate
method of contraception as outlined in Protocol Section 5.7.2 – Contraception,
for the course of the study starting with the first dose of study therapy through
180 days after the last dose of study therapy for the chemotherapy arm and 120
days for pembrolizumab (MK-3475) arm, whichever is later.
Note: Abstinence is acceptable if this is the usual lifestyle and preferred
contraception for the subject.
8. 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 180 days after the last dose of study
therapy for the chemotherapy arm and 120 days for pembrolizumab (MK-3475)
arm, whichever is later.
Note: Abstinence is acceptable if this is the usual lifestyle and preferred
contraception for the subject.
9. Demonstrate adequate organ function as defined in following table. All
screening labs should be performed within 10 days of treatment initiation.
Male/Female subjects with Microsatellite Instability-High (MSI-H) or Mismatch
Repair Deficient (dMMR) Colorectal Cancer will be enrolled in this trial.
Subject Inclusion Criteria
In order to be eligible for participation in this trial, the subject must:
1. Provide written informed consent for the trial.
Be male or female who is ≥ 18 years of age on the date of signing informed
consent. (Subjects in Taiwan aged at least 20 years)
2. Have locally confirmed MMR deficient (dMMR) or microsatellite instability
high (MSI-H) stage IV colorectal carcinoma
3. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0
or 1
4. Have life expectancy of at least 3 months
5. Have measurable disease at baseline based on RECIST 1.1 as determined by the
local site Investigator/radiology assessment.
6. Female subjects of childbearing potential must have a negative serum pregnancy
test within 72 hours prior to receiving the first dose of study medication.
7. Female subjects of childbearing potential must be willing to use an adequate
method of contraception as outlined in Protocol Section 5.7.2 – Contraception,
for the course of the study starting with the first dose of study therapy through
180 days after the last dose of study therapy for the chemotherapy arm and 120
days for pembrolizumab (MK-3475) arm, whichever is later.
Note: Abstinence is acceptable if this is the usual lifestyle and preferred
contraception for the subject.
8. 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 180 days after the last dose of study
therapy for the chemotherapy arm and 120 days for pembrolizumab (MK-3475)
arm, whichever is later.
Note: Abstinence is acceptable if this is the usual lifestyle and preferred
contraception for the subject.
9. Demonstrate adequate organ function as defined in following table. All
screening labs should be performed within 10 days of treatment initiation.
Exclusion Criteria
Subject Exclusion Criteria
The subject must be excluded from participating in the trial if the subject:
1. Has received prior systemic therapy for stage IV CRC. Subjects may have
received prior adjuvant chemotherapy for CRC as long as it was completed at least
6 months prior to randomization.
2. Is currently participating and receiving trial treatment in another study, or has
participated in a study of an investigational agent and received trial treatment, or
used an investigational device within 4 weeks of randomization.
3. 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 (eg. thyroxine, insulin, or
physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency, etc.) is not considered a form of systemic treatment.
4. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or
any other form of immunosuppressive therapy within 7 days prior to
randomization.
5. Has had radiation therapy within 4 weeks prior to randomization of study therapy
and who has not recovered to baseline from adverse events due to radiation therapy.
Subjects who have been given palliative radiotherapy to peripheral sites (e.g., bone
metastasis) may enter the study before 4 weeks have elapsed but must have
recovered from any acute adverse effects.
6. Has known active central nervous system (CNS) metastases and/or carcinomatous
meningitis. Subjects with previously treated brain metastases may participate
provided they have stable brain metastases [without evidence of progression by
imaging as confirmed by magnetic resonance imaging (MRI) if MRI was used at
prior imaging, or confirmed by computed tomography (CT) imaging if CT used at
prior imaging] at least four weeks prior to the first dose of trial treatment; also, any
neurologic symptoms must have returned to baseline], and have not used steroids
for brain metastases for at least 28 days prior to trial initiation. This exception does
not include carcinomatous meningitis, as subjects with carcinomatous meningitis
are excluded regardless of clinical stability.
7. Has had major surgical procedure, open biopsy or significant traumatic injury
within 28 days prior to randomization.
8. Has received prior therapy with an immune checkpoint inhibitor (e.g., anti-PD-1,
anti-PD-L1, anti-PD-L2 agent, or anti-CTLA-4 agent, etc).
9. Has another malignancy that is progressing or requires active treatment.
Exceptions include non-melanomatous skin cancer that has undergone potentially
curative therapy and in situ cervical carcinoma.
10. Has received a live vaccine within 30 days of planned start of study 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 a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2
antibodies), active chronic or acute Hepatitis B (e.g., HBsAg reactive) or Hepatitis
C (e.g., HCV RNA [qualitative] is detected).
13. Has known history of, or any evidence of interstitial lung disease or active,
non-infectious pneumonitis.
14. Has an active infection requiring systemic therapy.
15. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
16. Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the trial, starting with the screening visit through 180 days
after the last dose of trial treatment for standard of care or 120 days after the last
dose of pembrolizumab (MK-3475) arm.
The subject must be excluded from participating in the trial if the subject:
1. Has received prior systemic therapy for stage IV CRC. Subjects may have
received prior adjuvant chemotherapy for CRC as long as it was completed at least
6 months prior to randomization.
2. Is currently participating and receiving trial treatment in another study, or has
participated in a study of an investigational agent and received trial treatment, or
used an investigational device within 4 weeks of randomization.
3. 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 (eg. thyroxine, insulin, or
physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency, etc.) is not considered a form of systemic treatment.
4. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or
any other form of immunosuppressive therapy within 7 days prior to
randomization.
5. Has had radiation therapy within 4 weeks prior to randomization of study therapy
and who has not recovered to baseline from adverse events due to radiation therapy.
Subjects who have been given palliative radiotherapy to peripheral sites (e.g., bone
metastasis) may enter the study before 4 weeks have elapsed but must have
recovered from any acute adverse effects.
6. Has known active central nervous system (CNS) metastases and/or carcinomatous
meningitis. Subjects with previously treated brain metastases may participate
provided they have stable brain metastases [without evidence of progression by
imaging as confirmed by magnetic resonance imaging (MRI) if MRI was used at
prior imaging, or confirmed by computed tomography (CT) imaging if CT used at
prior imaging] at least four weeks prior to the first dose of trial treatment; also, any
neurologic symptoms must have returned to baseline], and have not used steroids
for brain metastases for at least 28 days prior to trial initiation. This exception does
not include carcinomatous meningitis, as subjects with carcinomatous meningitis
are excluded regardless of clinical stability.
7. Has had major surgical procedure, open biopsy or significant traumatic injury
within 28 days prior to randomization.
8. Has received prior therapy with an immune checkpoint inhibitor (e.g., anti-PD-1,
anti-PD-L1, anti-PD-L2 agent, or anti-CTLA-4 agent, etc).
9. Has another malignancy that is progressing or requires active treatment.
Exceptions include non-melanomatous skin cancer that has undergone potentially
curative therapy and in situ cervical carcinoma.
10. Has received a live vaccine within 30 days of planned start of study 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 a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2
antibodies), active chronic or acute Hepatitis B (e.g., HBsAg reactive) or Hepatitis
C (e.g., HCV RNA [qualitative] is detected).
13. Has known history of, or any evidence of interstitial lung disease or active,
non-infectious pneumonitis.
14. Has an active infection requiring systemic therapy.
15. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
16. Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the trial, starting with the screening visit through 180 days
after the last dose of trial treatment for standard of care or 120 days after the last
dose of pembrolizumab (MK-3475) arm.
The Estimated Number of Participants
-
Taiwan
10 participants
-
Global
300 participants
