Clinical Trials List
Protocol NumberMK-3475-042
NCT Number(ClinicalTrials.gov Identfier)NCT02220894
2014-10-01 - 2023-03-16
Phase III
Terminated5
ICD-10C34.90
Malignant neoplasm of unspecified part of unspecified bronchus or lung
ICD-10C34.91
Malignant neoplasm of unspecified part of right bronchus or lung
ICD-10C34.92
Malignant neoplasm of unspecified part of left bronchus or lung
ICD-10C7A.090
Malignant carcinoid tumor of the bronchus and lung
ICD-10Z51.12
Encounter for antineoplastic immunotherapy
ICD-9162.9
Malignant neoplasm of bronchus and lung, unspecified
A Randomized, Open Label, Phase III Study of Overall Survival Comparing Pembrolizumab (MK-3475) versus Platinum Based Chemotherapy in Treatment Naïve Subjects with PD-L1 Positive Advanced or Metastatic Non-Small Cell Lung Cancer (Keynote 042)
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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
Principal Investigator
Co-Principal Investigator
- Yung-Hung Luo Division of Hematology & Oncology
- Chia-I Shen Division of Hematology & Oncology
- Heng-Sheng Chao Division of Hematology & Oncology
- Chao-Hua Chiu Division of Hematology & Oncology
- Chi-Lu Chiang Division of Hematology & Oncology
- 蔡俊明 Division of Hematology & Oncology
- 蕭慈慧 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Yu-Chao Lin Division of Thoracic Medicine
- Chen Chia-Hung Division of Thoracic Medicine
- 陳鴻仁 Division of Thoracic Medicine
- Chih-Yen Tu Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 陳焜結 Division of Thoracic Medicine
- KUO-HSUAN HSU Division of Thoracic Medicine
- TSUNG -YING YANG Division of Thoracic Medicine
- JENG-SEN TSENG Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Wen-Pin Su Division of Hematology & Oncology
- Yu-Min Yeh Division of Hematology & Oncology
- Wei-Pang Chung Division of Hematology & Oncology
- Shang-Yin Wu Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Chong-Jen Yu Division of Thoracic Medicine
- 廖唯昱 Division of Thoracic Medicine
- Chia-Chi Lin Division of Hematology & Oncology
- JIN-YUAN SHIH Division of Thoracic Medicine
- 林宗哲 Division of Thoracic Medicine
- Jih-Hsiang Lee Division of Hematology & Oncology
- CHAO-CHI HO CHAO-CHI HO Division of Thoracic Medicine
- 林育麟 Division of Hematology & Oncology
- 陳冠宇 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
Non-Small Cell Lung Cancer (NSCLC)
Objectives
1. Primary Objective(s) & Hypothesis(es)
Objective: To compare the overall survival (OS) in subjects with
PD-L1 strongly positive, 1L advanced/metastatic NSCLC treated with
pembrolizumab compared to standard of care (SOC) chemotherapies.
Hypothesis: Pembrolizumab prolongs OS in subjects with PD-L1
strongly positive NSCLC compared to SOC chemotherapy.
The study is considered to have met its primary objective in the
primary population of subjects with strongly positive PD-L1
expression if pembrolizumab is superior to SOC in OS at an interim
analysis or the final analysis.
2. Secondary Objective(s) & Hypothesis(es)
1) Objective: To compare the progression-free survival (PFS) by
RECIST 1.1 as assessed by independent radiologists’ review in
subjects with PD-L1 strongly positive, 1L advanced/metastatic
NSCLC treated with pembrolizumab compared to SOC
chemotherapy.
Hypothesis: Pembrolizumab prolongs PFS by RECIST 1.1
(independent radiologists’ review) in subjects with PD-L1
strongly positive NSCLC compared to SOC chemotherapy.
2) Objective: To compare the OS in subjects with PD-L1 positive
(strong and weak), 1L advanced/metastatic NSCLC treated with
pembrolizumab compared to SOC chemotherapies.
Hypothesis: MK 3475 prolongs OS in subjects with PD-L1
positive (strong and weak) NSCLC compared to SOC
chemotherapy.
3) Objective: To compare the PFS as assessed by RECIST 1.1 by
independent radiologists’ review in subjects with PD-L1 positive
(strong and weak), 1L advanced/metastatic NSCLC treated with
pembrolizumab compared to SOC chemotherapy.
Hypothesis: Pembrolizumab prolongs PFS by RECIST 1.1
(independent radiologists’ review) in subjects with PD-L1 positive
(strong and weak) NSCLC compared to SOC chemotherapy.
4) Objective: To Evaluate the safety and tolerability profile of
pembrolizumab in subjects with 1L advanced/metastatic PD-L1
positive NSCLC.
Hypothesis: Pembrolizumab has acceptable safety and tolerability
in metastatic PD-L1 positive NSCLC administered in the first line
setting
Test Drug
MK-3475
Active Ingredient
MK-3475
Dosage Form
lyophilized Powder for Injection
Dosage
25mg/mL
Endpoints
Primary Outcome Measures :
1. Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥50% [ Time Frame: Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months) ]
OS was determined for participants with a TPS of ≥50% and was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the interim analysis were censored at the date of the last follow-up. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was OS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The OS for participants with a TPS ≥50% is presented.
2. Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥20% [ Time Frame: Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months) ]
OS was determined for participants with a TPS of ≥20% and was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the interim analysis were censored at the date of the last follow-up. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was OS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The OS for participants with a TPS ≥20% is presented.
3. Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥1% [ Time Frame: Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months) ]
OS was determined for participants with a TPS of ≥1% and was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the interim analysis were censored at the date of the last follow-up. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was OS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The OS for participants with a TPS ≥1% is presented.
1. Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥50% [ Time Frame: Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months) ]
OS was determined for participants with a TPS of ≥50% and was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the interim analysis were censored at the date of the last follow-up. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was OS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The OS for participants with a TPS ≥50% is presented.
2. Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥20% [ Time Frame: Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months) ]
OS was determined for participants with a TPS of ≥20% and was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the interim analysis were censored at the date of the last follow-up. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was OS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The OS for participants with a TPS ≥20% is presented.
3. Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥1% [ Time Frame: Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months) ]
OS was determined for participants with a TPS of ≥1% and was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the interim analysis were censored at the date of the last follow-up. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was OS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The OS for participants with a TPS ≥1% is presented.
Inclution Criteria
Inclusion criteria:
• Histologically- or cytologically-confirmed diagnosis of advanced or metastatic NSCLC
• PD-L1 positive tumor
• Measureable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Life expectancy of at least 3 months
• No prior systemic chemotherapy for the treatment of the participant's advanced or metastatic disease (treatment with chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as completed at least 6 months prior to diagnosis of advanced or metastatic disease)
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Adequate organ function
• No prior malignancy, with the exception of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, or in situ cancer, or has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy
• Submission of formalin-fixed diagnostic tumor tissue (in the case of participants having received adjuvant systemic therapy, the tissue should be taken after completion of this therapy)
• Female participants of childbearing potential must have a negative urine or serum pregnancy test and must be willing to use two adequate barrier methods of contraception or a barrier method plus a hormonal method starting with the screening visit through 120 days after the last dose of pembrolizumab or 180 days after the last dose of chemotherapeutic agents used in the study
• Male participants with a female partner(s) of child-bearing potential must be willing to use two adequate barrier methods of contraception from screening through 120 days after the last dose of pembrolizumab or 180 days after the last dose of chemotherapeutic agents used in the study
• Histologically- or cytologically-confirmed diagnosis of advanced or metastatic NSCLC
• PD-L1 positive tumor
• Measureable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Life expectancy of at least 3 months
• No prior systemic chemotherapy for the treatment of the participant's advanced or metastatic disease (treatment with chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as completed at least 6 months prior to diagnosis of advanced or metastatic disease)
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Adequate organ function
• No prior malignancy, with the exception of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, or in situ cancer, or has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy
• Submission of formalin-fixed diagnostic tumor tissue (in the case of participants having received adjuvant systemic therapy, the tissue should be taken after completion of this therapy)
• Female participants of childbearing potential must have a negative urine or serum pregnancy test and must be willing to use two adequate barrier methods of contraception or a barrier method plus a hormonal method starting with the screening visit through 120 days after the last dose of pembrolizumab or 180 days after the last dose of chemotherapeutic agents used in the study
• Male participants with a female partner(s) of child-bearing potential must be willing to use two adequate barrier methods of contraception from screening through 120 days after the last dose of pembrolizumab or 180 days after the last dose of chemotherapeutic agents used in the study
Exclusion Criteria
Exclusion criteria:
• Epidermal growth factor receptor (EGFR)-sensitizing mutation and/or is echinoderm microtubule-associated protein-like 4(EML4) gene/anaplastic lymphoma kinase (ALK) gene fusion positive
• Currently participating or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of study therapy
• No tumor specimen evaluable for PD-L1 expression by the central study laboratory
• Squamous histology and received carboplatin in combination with paclitaxel in the adjuvant setting
• Is receiving systemic steroid therapy ≤3 days prior to the first dose of study therapy or receiving any other form of immunosuppressive medication with the exception of daily steroid replacement therapy
• The NSCLC can be treated with curative intent with either surgical resection and/or chemoradiation
• Expected to require any other form of systemic or localized antineoplastic therapy while on study
• Any prior systemic cytotoxic chemotherapy, biological therapy or major surgery within 3 weeks of the first dose of study therapy; received lung radiation therapy >30 Gy within 6 months of the first dose of study therapy
• Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
• Known central nervous system metastases and/or carcinomatous meningitis
• Active autoimmune disease that has required systemic treatment in the past 2 years
• Had allogeneic tissue/solid organ transplantation
• Interstitial lung disease or history of pneumonitis that has required oral or IV steroids
• Has received or will receive a live vaccine within 30 days prior to the first study therapy (seasonal flu vaccines that do not contain live vaccine are permitted)
• Active infection requiring intravenous systemic therapy
• Known history of human immunodeficiency virus (HIV)
• Known active Hepatitis B or C
• Regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol)
• Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study
• Epidermal growth factor receptor (EGFR)-sensitizing mutation and/or is echinoderm microtubule-associated protein-like 4(EML4) gene/anaplastic lymphoma kinase (ALK) gene fusion positive
• Currently participating or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of study therapy
• No tumor specimen evaluable for PD-L1 expression by the central study laboratory
• Squamous histology and received carboplatin in combination with paclitaxel in the adjuvant setting
• Is receiving systemic steroid therapy ≤3 days prior to the first dose of study therapy or receiving any other form of immunosuppressive medication with the exception of daily steroid replacement therapy
• The NSCLC can be treated with curative intent with either surgical resection and/or chemoradiation
• Expected to require any other form of systemic or localized antineoplastic therapy while on study
• Any prior systemic cytotoxic chemotherapy, biological therapy or major surgery within 3 weeks of the first dose of study therapy; received lung radiation therapy >30 Gy within 6 months of the first dose of study therapy
• Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
• Known central nervous system metastases and/or carcinomatous meningitis
• Active autoimmune disease that has required systemic treatment in the past 2 years
• Had allogeneic tissue/solid organ transplantation
• Interstitial lung disease or history of pneumonitis that has required oral or IV steroids
• Has received or will receive a live vaccine within 30 days prior to the first study therapy (seasonal flu vaccines that do not contain live vaccine are permitted)
• Active infection requiring intravenous systemic therapy
• Known history of human immunodeficiency virus (HIV)
• Known active Hepatitis B or C
• Regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol)
• Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study
The Estimated Number of Participants
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Taiwan
27 participants
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Global
1240 participants
