- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03850444
Study of Pembrolizumab (MK-3475) Versus Platinum-Based Chemotherapy for Participants With Programmed Cell Death-Ligand 1 (PD-L1)-Positive Advanced or Metastatic Non-Small Cell Lung Cancer (MK-3475-042/KEYNOTE-042)-China Extension Study
August 22, 2023 updated by: Merck Sharp & Dohme LLC
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)
In the China extension study, Chinese participants with programmed cell death ligand 1 (PD-L1)-positive non-small cell lung cancer (NSCLC) will be randomized to receive single agent pembrolizumab for up to 35 treatments or standard of care (SOC) platinum-based chemotherapy (carboplatin + paclitaxel or carboplatin + pemetrexed for 4 to 6 21-day cycles).
Chinese participants in the platinum-based chemotherapy arms with non-squamous tumor histologies may receive pemetrexed maintenance therapy after the 4 to 6 cycles of chemotherapy.
The primary extension study hypothesis is that pembrolizumab prolongs overall survival (OS) compared to SOC chemotherapy in Chinese participants.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
The China extension study enrolled 262 participants.
Of the 262 total participants enrolled, 92 were also previously enrolled in the global study for MK-3475-042 (NCT02220894).
Study Type
Interventional
Enrollment (Actual)
262
Phase
- Phase 3
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion criteria:
- Histologically- or cytologically-confirmed diagnosis of advanced or metastatic NSCLC
- PD-L1 positive tumor
- Measurable 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 childbearing 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:
- 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-PDL2, 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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Pembrolizumab
Participants receive pembrolizumab 200 mg by IV infusion on Day 1 every 3 weeks (Q3W) for a maximum of 35 cycles (21-day cycles).
Participants who stop the initial course of pembrolizumab due to complete response or complete the initial course of pembrolizumab and have stable disease, but progress after discontinuation, are eligible for a second course of pembrolizumab for up to an additional 1 year (17 additional 21-day cycles).
|
Other Names:
|
Active Comparator: SOC Treatment
Participants receive carboplatin at target dose Area Under the Curve (AUC 5) (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + paclitaxel 200 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles) OR carboplatin target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles).
Participants with non-squamous histologies receive optional additional maintenance treatment with pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W.
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Other Names:
Other Names:
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥50%
Time Frame: Up to 23.2 months
|
OS was determined for participants with a TPS of ≥50% and was defined as the time from randomization until death due to any cause.
Participants without documented death at the time of the 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 OS for participants with a TPS ≥50% is presented.
|
Up to 23.2 months
|
Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥20%
Time Frame: Up to 23.2 months
|
OS was determined for participants with a TPS of ≥20% and was defined as the time from randomization until death due to any cause.
Participants without documented death at the time of the 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 OS for participants with a TPS ≥20% is presented.
|
Up to 23.2 months
|
Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥1%
Time Frame: Up to 23.2 months
|
OS was determined for participants with a TPS of ≥1% and was defined as the time from randomization until death due to any cause.
Participants without documented death at the time of the 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 OS for participants with a TPS ≥1% is presented.
|
Up to 23.2 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥50%
Time Frame: Up to 23.2 months
|
PFS was determined for participants with a TPS of ≥50% and was defined as the time from randomization until the first documented progressive disease (PD) or death due to any cause, whichever occurred first.
Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.
In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm.
The appearance of one or more new lesions or progression in non-target lesions was also considered PD.
The PFS per RECIST 1.1 was calculated using the product-limit (Kaplan-Meier) method for censored data.
The PFS for participants with a TPS ≥50% is presented.
|
Up to 23.2 months
|
Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥20%
Time Frame: Up to 23.2 months
|
PFS was determined for participants with a TPS of ≥20% and was defined as the time from randomization until the first documented progressive disease (PD) or death due to any cause, whichever occurred first.
Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.
In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm.
The appearance of one or more new lesions or progression in non-target lesions was also considered PD.
The PFS per RECIST 1.1 was calculated using the product-limit (Kaplan-Meier) method for censored data.
The PFS for participants with a TPS ≥20% is presented.
|
Up to 23.2 months
|
Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥1%
Time Frame: Up to 23.2 months
|
PFS was determined for participants with a TPS of ≥1% and was defined as the time from randomization until the first documented progressive disease (PD) or death due to any cause, whichever occurred first.
Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.
In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm.
The appearance of one or more new lesions or progression in non-target lesions was also considered PD.
The PFS per RECIST 1.1 was calculated using the product-limit (Kaplan-Meier) method for censored data.
The PFS for participants with a TPS ≥1% is presented.
|
Up to 23.2 months
|
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥50%
Time Frame: Up to 23.2 months
|
ORR was determined for participants with a TPS of ≥50%.
ORR was determined per RECIST 1.1 and was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target and non-target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1.
The percentage of participants who had a TPS ≥50% and who experienced a CR or PR is presented.
|
Up to 23.2 months
|
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥20%
Time Frame: Up to 23.2 months
|
ORR was determined for participants with a TPS of ≥20%.
ORR was determined per RECIST 1.1 and was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target and non-target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1.
The percentage of participants who had a TPS ≥20% and who experienced a CR or PR is presented.
|
Up to 23.2 months
|
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥1%
Time Frame: Up to 23.2 months
|
ORR was determined for participants with a TPS of ≥1%.
ORR was determined per RECIST 1.1 and was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target and non-target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1.
The percentage of participants who had a TPS ≥1% and who experienced a CR or PR is presented.
|
Up to 23.2 months
|
Number of Participants Who Experienced At Least One Adverse Event (AE)
Time Frame: Up to 59.7 months
|
An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment.
An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure.
Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE.
The number of participants who experienced at least one AE is presented.
|
Up to 59.7 months
|
Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
Time Frame: Up to 56.7 months
|
An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment.
An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure.
Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE.
The number of participants who discontinued study treatment due to an AE is presented.
|
Up to 56.7 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
August 1, 2016
Primary Completion (Actual)
September 4, 2018
Study Completion (Actual)
September 8, 2022
Study Registration Dates
First Submitted
February 20, 2019
First Submitted That Met QC Criteria
February 20, 2019
First Posted (Actual)
February 21, 2019
Study Record Updates
Last Update Posted (Actual)
September 18, 2023
Last Update Submitted That Met QC Criteria
August 22, 2023
Last Verified
August 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Neoplasms
- Lung Diseases
- Neoplasms by Site
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Carcinoma, Bronchogenic
- Bronchial Neoplasms
- Lung Neoplasms
- Carcinoma, Non-Small-Cell Lung
- Molecular Mechanisms of Pharmacological Action
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Antineoplastic Agents
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antineoplastic Agents, Phytogenic
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Folic Acid Antagonists
- Carboplatin
- Paclitaxel
- Pembrolizumab
- Pemetrexed
Other Study ID Numbers
- 3475-042 China Extension
- 152877 (Registry Identifier: JAPIC-CTI)
- MK-3475-042 (Other Identifier: Merck Protocol Number)
- KEYNOTE-042 (Other Identifier: Merck)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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