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)

September 28, 2023 updated by: Merck Sharp & Dohme LLC

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)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

559

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

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 180 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 95 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 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

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: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Drug: Paclitaxel
IV infusion
Other Names:
  • TAXOL®
Drug: Nab-paclitaxel
IV infusion
Other Names:
  • ABRAXANE®
Drug: Saline placebo for pembrolizumab
IV infusion
Drug: Carboplatin
IV infusion Carboplatin dose should not to exceed 900 mg.
Other Names:
  • PARAPLATIN®
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.
Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • KEYTRUDA®
Drug: Paclitaxel
IV infusion
Other Names:
  • TAXOL®
Drug: Nab-paclitaxel
IV infusion
Other Names:
  • ABRAXANE®
Drug: Carboplatin
IV infusion Carboplatin dose should not to exceed 900 mg.
Other Names:
  • PARAPLATIN®

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 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.
Up to approximately 19 months (Database cutoff date of 03-Apr-2018)
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.
Up to approximately 19 months (Database cutoff date of 03-Apr-2018)

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 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.
Up to approximately 19 months (Database cutoff date of 03-Apr-2018)
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.
Up to approximately 19 months (Database cutoff date of 03-Apr-2018)
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.
Up to approximately 19 months (Database cutoff date of 03-Apr-2018)
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.
Up to approximately 19 months (Database cutoff date of 03-Apr-2018)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merck Sharp & Dohme LLC

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.

General Publications

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)

June 9, 2016

Primary Completion (Actual)

April 3, 2018

Study Completion (Actual)

September 14, 2023

Study Registration Dates

First Submitted

May 15, 2016

First Submitted That Met QC Criteria

May 15, 2016

First Posted (Estimated)

May 17, 2016

Study Record Updates

Last Update Posted (Actual)

October 6, 2023

Last Update Submitted That Met QC Criteria

September 28, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 3475-407
  • 173568 (Registry Identifier: JAPIC-CTI)
  • MK-3475-407 (Other Identifier: Merck Protocol Number)
  • KEYNOTE-407 (Other Identifier: Merck)
  • 2016-000229-38 (EudraCT Number)

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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