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
Condition: Non-small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Pembrolizumab; Paclitaxel; Nab-paclitaxel; Carboplatin; Saline placebo for pembrolizumab
Intervention description: IV infusion; IV infusion; IV infusion; IV infusion Carboplatin dose should not exceed 900 mg.; IV infusion
Intervention MeSH terms: Paclitaxel; Albumin-Bound Paclitaxel; Carboplatin; Pembrolizumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 125.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Programmed Cell Death-1 (PD1, PD-1); Programmed Death-Ligand 1 (PDL1, PD-L1)

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.
    

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.