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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02775435
Recruitment Status : Active, not recruiting
First Posted : May 17, 2016
Results First Posted : April 10, 2019
Last Update Posted : April 1, 2020
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE May 15, 2016
First Posted Date  ICMJE May 17, 2016
Results First Submitted Date  ICMJE February 19, 2019
Results First Posted Date  ICMJE April 10, 2019
Last Update Posted Date April 1, 2020
Actual Study Start Date  ICMJE June 9, 2016
Actual Primary Completion Date April 3, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 18, 2019)
  • Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [ Time Frame: Up to approximately 19 months (Database cutoff date of 03-Apr-2018) ]
    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.
  • Overall Survival (OS) [ Time Frame: Up to approximately 19 months (Database cutoff date of 03-Apr-2018) ]
    OS was defined as the time from randomization to death due to any cause. OS is presented.
Original Primary Outcome Measures  ICMJE
 (submitted: May 15, 2016)
  • Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by a blinded central imaging vendor [ Time Frame: Up to approximately 2 years ]
  • Overall Survival (OS) [ Time Frame: Up to approximately 2 years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 18, 2019)
  • Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [ Time Frame: Up to approximately 19 months (Database cutoff date of 03-Apr-2018) ]
    ORR was defined as the percentage of participants 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) [ Time Frame: Up to approximately 19 months (Database cutoff date of 03-Apr-2018) ]
    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) [ Time Frame: Up to approximately 19 months (Database cutoff date of 03-Apr-2018) ]
    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.
  • Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) [ Time Frame: Up to approximately 19 months (Database cutoff date of 03-Apr-2018) ]
    The number of participants who discontinued study treatment due to an AE is presented.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 15, 2016)
Objective Response Rate (ORR) per RECIST 1.1 as assessed by a blinded central imaging vendor [ Time Frame: Up to approximately 2 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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)
Official Title  ICMJE 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)
Brief Summary

This is a study of carboplatin and paclitaxel or nano particle albumin-bound paclitaxel (nab-paclitaxel) with or without pembrolizumab (MK-3475, KEYTRUDA®) in 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).

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 Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Non-small Cell Lung Cancer
Intervention  ICMJE
  • Biological: Pembrolizumab
    IV infusion
    Other Names:
    • MK-3475
    • KEYTRUDA®
  • Drug: Paclitaxel
    IV infusion
    Other Name: TAXOL®
  • Drug: Nab-paclitaxel
    IV infusion
    Other Name: ABRAXANE®
  • Drug: Carboplatin
    IV infusion Carboplatin dose should not to exceed 900 mg.
    Other Name: PARAPLATIN®
  • Drug: Saline placebo for pembrolizumab
    IV infusion
Study Arms  ICMJE
  • 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 AUC 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles.
    Interventions:
    • Biological: Pembrolizumab
    • Drug: Paclitaxel
    • Drug: Nab-paclitaxel
    • Drug: Carboplatin
  • 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.
    Interventions:
    • Drug: Paclitaxel
    • Drug: Nab-paclitaxel
    • Drug: Carboplatin
    • Drug: Saline placebo for pembrolizumab
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: March 18, 2019)
559
Original Estimated Enrollment  ICMJE
 (submitted: May 15, 2016)
560
Estimated Study Completion Date  ICMJE February 15, 2021
Actual Primary Completion Date April 3, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Has a histologically or cytologically confirmed diagnosis of stage IV (M1a or M1b-American Joint Committee on Cancer [AJCC] 7th edition) 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 120 days after the last dose of study drug.
  • 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 drug through 120 days after the last dose of study drug. 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 Gy within 6 months of the first dose of study drug.
  • Completed palliative radiotherapy within 7 days of the first dose of study drug.
  • 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 or C. Active Hepatitis B.
  • Is, at the time of signing 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.
  • Is pregnant or breastfeeding, or expecting to conceive or father children while on study drug and for the required duration of contraception after the last dose of study drug.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries Australia,   Canada,   China,   France,   Germany,   Hungary,   Italy,   Japan,   Korea, Republic of,   Mexico,   Netherlands,   Poland,   Russian Federation,   Spain,   Thailand,   Turkey,   United States
 
Administrative Information
NCT Number  ICMJE NCT02775435
Other Study ID Numbers  ICMJE 3475-407
2016-000229-38 ( EudraCT Number )
173568 ( Registry Identifier: JAPIC-CTI )
MK-3475-407 ( Other Identifier: Merck Protocol Number )
KEYNOTE-407 ( Other Identifier: Merck )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme Corp.
PRS Account Merck Sharp & Dohme Corp.
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP