Back to resultsA 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
Primary Purpose
Non-small Cell Lung Cancer
Status
Completed
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Pembrolizumab
Paclitaxel
Nab-paclitaxel
Carboplatin
Saline placebo for pembrolizumab
Sponsored by
About this trial
This is an interventional treatment trial for Non-small Cell Lung Cancer focused on measuring Programmed Cell Death-1 (PD1, PD-1), Programmed Death-Ligand 1 (PDL1, PD-L1)
Eligibility Criteria
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.
Sites / Locations
- Zhongshan Hospital Fudan University
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Pembrolizumab + Chemotherapy
Chemotherapy
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
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.
Overall Survival (OS)
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.
Secondary Outcome Measures
Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
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.
Duration of Response (DOR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
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.
Number of Participants Who Experienced an Adverse Event (AE)
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.
Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
The number of participants who discontinued study treatment due to an AE is presented.
Full Information
NCT ID
NCT03875092
First Posted
March 13, 2019
Last Updated
September 28, 2023
Sponsor
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT03875092
Brief Title
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
Official Title
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)
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
April 21, 2017 (Actual)
Primary Completion Date
September 30, 2020 (Actual)
Study Completion Date
September 14, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
Detailed Description
The MK-3475-407-China Extension Study has enrolled a total of 125 participants, of which 15 participants have been also previously enrolled in the MK-3475-407 global study (NCT02775435).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-small Cell Lung Cancer
Keywords
Programmed Cell Death-1 (PD1, PD-1), Programmed Death-Ligand 1 (PDL1, PD-L1)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
125 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Pembrolizumab + Chemotherapy
Arm Type
Experimental
Arm Description
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.
Arm Title
Chemotherapy
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
MK-3475, KEYTRUDA®
Intervention Description
IV infusion
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Other Intervention Name(s)
TAXOL®
Intervention Description
IV infusion
Intervention Type
Drug
Intervention Name(s)
Nab-paclitaxel
Other Intervention Name(s)
ABRAXANE®
Intervention Description
IV infusion
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Other Intervention Name(s)
PARAPLATIN®
Intervention Description
IV infusion Carboplatin dose should not exceed 900 mg.
Intervention Type
Drug
Intervention Name(s)
Saline placebo for pembrolizumab
Intervention Description
IV infusion
Primary Outcome Measure Information:
Title
Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Description
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.
Time Frame
Up to approximately 33 months (Database cutoff date of 30-Sep-2020)
Title
Overall Survival (OS)
Description
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.
Time Frame
Up to approximately 39 months (Database cutoff date of 30-Sep-2020)
Secondary Outcome Measure Information:
Title
Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Description
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.
Time Frame
Up to approximately 33 months (Database cutoff date of 30-Sep-2020)
Title
Duration of Response (DOR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Description
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.
Time Frame
Up to approximately 30 months (Database cutoff date of 30-Sep-2020)
Title
Number of Participants Who Experienced an Adverse Event (AE)
Description
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.
Time Frame
Up to approximately 31 months (Database cutoff date of 30-Sep-2020)
Title
Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
Description
The number of participants who discontinued study treatment due to an AE is presented.
Time Frame
Up to approximately 29 months (Database cutoff date of 30-Sep-2020)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
Facility Information:
Facility Name
Zhongshan Hospital Fudan University
City
Shanghai
ZIP/Postal Code
200032
Country
China
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Citations:
PubMed Identifier
34661177
Citation
Cheng Y, Zhang L, Hu J, Wang D, Hu C, Zhou J, Wu L, Cao L, Liu J, Zhang H, Sun H, Wang Z, Gao H, Sun Y, Li B, Hu X, Schwarzenberger P, Paz-Ares L. Pembrolizumab Plus Chemotherapy for Chinese Patients With Metastatic Squamous NSCLC in KEYNOTE-407. JTO Clin Res Rep. 2021 Sep 25;2(10):100225. doi: 10.1016/j.jtocrr.2021.100225. eCollection 2021 Oct.
Results Reference
result
Links:
URL
https://www.merckclinicaltrials.com
Description
Merck Clinical Trials Information
Learn more about this trial
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
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