- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03875092
A Study of Carboplatin-Paclitaxel/Nab-Paclitaxel Chemotherapy With or Without Pembrolizumab (MK-3475) in Adults With First Line Metastatic Squamous Non-small Cell Lung Cancer (MK-3475-407/KEYNOTE-407)-China Extension Study
A Randomized, Double-Blind, Phase III Study of Carboplatin-Paclitaxel/Nab-Paclitaxel Chemotherapy With or Without Pembrolizumab (MK-3475) in First Line Metastatic Squamous Non-small Cell Lung Cancer Subjects (KEYNOTE-407)
In this China extension study, carboplatin and paclitaxel or nano particle albumin-bound paclitaxel (nab-paclitaxel) with or without pembrolizumab (MK-3475, KEYTRUDA®) will be administered to Chinese adults with first line metastatic squamous non-small cell lung cancer (NSCLC).
The primary hypotheses are that treatment with pembrolizumab prolongs: 1) Progression-free Survival (PFS) by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by a blinded central imaging vendor compared to placebo, and 2) Overall Survival (OS) in Chinese participants.
After analysis of interim results was conducted, the protocol was amended (Amendment 5) to allow participants the option to discontinue placebo in the control arm and to switch to pembrolizumab in the event of documented progressive disease as assessed by central review.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Shanghai, China, 200032
- Zhongshan Hospital Fudan University
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Has a histologically or cytologically confirmed diagnosis of stage IV (M1a or M1b-American Joint Committee on Cancer [AJCC]) squamous NSCLC.
- Has measurable disease based on RECIST 1.1 as determined by the local site investigator/radiology assessment.
- Has not received prior systemic treatment for metastatic NSCLC.
- Has provided tumor tissue from locations not radiated prior to biopsy.
- Has a life expectancy of at least 3 months.
- Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status.
- Has adequate organ function.
- If female of childbearing potential, is willing to use an adequate method of contraception for the course of the study through 180 days after the last dose of study treatment.
- If male with a female partner(s) of child-bearing potential, must agree to use an adequate method of contraception starting with the first dose of study treatment through 95 days after the last dose of study treatment. Males with pregnant partners must agree to use a condom; no additional method of contraception is required for the pregnant partner.
Exclusion Criteria:
- Has non-squamous histology NSCLC.
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to administration of pembrolizumab.
- Before the first dose of study drug: a) Has received prior systemic cytotoxic chemotherapy for metastatic disease; b) Has received other targeted or biological antineoplastic therapy (e.g., erlotinib, crizotinib, cetuximab) for metastatic disease; c) Has had major surgery (<3 weeks prior to first dose).
- Received radiation therapy to the lung that is >30 Gray (Gy) within 6 months of the first dose of study treatment.
- Completed palliative radiotherapy within 7 days of the first dose of study treatment.
- Is expected to require any other form of antineoplastic therapy while on study.
- Has received a live-virus vaccination within 30 days of planned treatment start.
- Has a known history of prior malignancy except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy.
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- Has pre-existing peripheral neuropathy that is ≥ Grade 2 by Common Terminology Criteria for Adverse Events (CTCAE) Version 4 criteria.
- Previously had a severe hypersensitivity reaction to treatment with another monoclonal antibody.
- Has a known sensitivity to any component of carboplatin or paclitaxel or nab-paclitaxel.
- Has active autoimmune disease that has required systemic treatment in past 2 years.
- Is on chronic systemic steroids.
- Had prior treatment with any other anti-programmed cell death 1 (anti-PD-1), or programmed cell death ligand 1 (PD-L1) or PD-L2 agent or an antibody or a small molecule targeting other immuno-regulatory receptors or mechanisms.
- Has participated in any other pembrolizumab trial and has been treated with pembrolizumab.
- Has an active infection requiring therapy.
- Has known history of Human Immunodeficiency Virus (HIV).
- Has known active Hepatitis B virus (HBV) or Hepatitis C virus (HCV) infection.
- Is, at the time of providing documented informed consent, a regular user (including "recreational use") of any illicit drugs or has a recent history (within the last year) of substance abuse (including alcohol).
- Has interstitial lung disease or a history of pneumonitis that required oral or intravenous glucocorticoids to assist with management.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Pembrolizumab + Chemotherapy
Participants receive pembrolizumab 200 mg by intravenous (IV) infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS Investigator's choice of paclitaxel (200 mg/m^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) or nab-paclitaxel (100 mg/m^2 by IV infusion on Days 1, 8, 15 of each 21-day cycle for 4 cycles) PLUS carboplatin Area Under the Curve (AUC) 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles.
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IV infusion
Other Names:
IV infusion
Other Names:
IV infusion
Other Names:
IV infusion Carboplatin dose should not exceed 900 mg.
Other Names:
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Active Comparator: Chemotherapy
Participants receive normal saline by IV infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS Investigator's choice of paclitaxel (200 mg/m^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) or nab-paclitaxel (100 mg/m^2 by IV infusion on Days 1, 8, 15 of each 21-day cycle for 4 cycles) PLUS carboplatin AUC 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles.
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IV infusion
Other Names:
IV infusion
Other Names:
IV infusion Carboplatin dose should not exceed 900 mg.
Other Names:
IV infusion
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Time Frame: Up to approximately 33 months (Database cutoff date of 30-Sep-2020)
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PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first.
Per Response Criteria in Solid Tumors version 1.1 (RECIST 1.1), PD was defined as ≥20% increase in the sum of diameters of target lesions.
In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm.
Note: The appearance of ≥1 new lesions was also considered PD.
PFS as assessed by blinded independent central review per RECIST 1.1 is presented.
Data are from the product-limit (Kaplan-Meier) method for censored data.
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Up to approximately 33 months (Database cutoff date of 30-Sep-2020)
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Overall Survival (OS)
Time Frame: Up to approximately 39 months (Database cutoff date of 30-Sep-2020)
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OS was defined as the time from randomization to death due to any cause.
OS is presented.
Data are from the product-limit (Kaplan-Meier) method for censored data.
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Up to approximately 39 months (Database cutoff date of 30-Sep-2020)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Time Frame: Up to approximately 33 months (Database cutoff date of 30-Sep-2020)
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ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) as assessed by RECIST 1.1.
ORR as assessed by blinded independent central review per RECIST 1.1 is presented.
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Up to approximately 33 months (Database cutoff date of 30-Sep-2020)
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Duration of Response (DOR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Time Frame: Up to approximately 30 months (Database cutoff date of 30-Sep-2020)
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For participants who demonstrated a confirmed response (Complete Response [CR]: Disappearance of all target lesions or Partial Response [PR]: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until disease progression as assessed by RECIST 1.1 or death.
DOR as assessed by blinded independent central review per RECIST 1.1 is presented.
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Up to approximately 30 months (Database cutoff date of 30-Sep-2020)
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Number of Participants Who Experienced an Adverse Event (AE)
Time Frame: Up to approximately 31 months (Database cutoff date of 30-Sep-2020)
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An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment.
The number of participants who experienced an AE is presented.
Data are from the product-limit (Kaplan-Meier) method for censored data.
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Up to approximately 31 months (Database cutoff date of 30-Sep-2020)
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Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
Time Frame: Up to approximately 29 months (Database cutoff date of 30-Sep-2020)
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The number of participants who discontinued study treatment due to an AE is presented.
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Up to approximately 29 months (Database cutoff date of 30-Sep-2020)
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
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
- Antineoplastic Agents
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antineoplastic Agents, Phytogenic
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Carboplatin
- Paclitaxel
- Pembrolizumab
- Albumin-Bound Paclitaxel
Other Study ID Numbers
- 3475-407 China Extension
- 173568 (Registry Identifier: JAPIC-CTI)
- MK-3475-407 (Other Identifier: Merck Protocol Number)
- KEYNOTE-407 (Other Identifier: Merck)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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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