Study of Pembrolizumab (MK-3475) Versus Platinum-Based Chemotherapy for Participants With Programmed Cell Death-Ligand 1 (PD-L1)-Positive Advanced or Metastatic Non-Small Cell Lung Cancer (MK-3475-042/KEYNOTE-042)
Condition: Non-small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: pembrolizumab; carboplatin; paclitaxel; pemetrexed
Intervention MeSH terms: Paclitaxel; Carboplatin; Pembrolizumab; Pemetrexed
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 1274.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: PD-1; PD1; PD-L1; PDL1

Summary:

      In this study, participants with programmed cell death ligand 1 (PD-L1)-positive non-small
      cell lung cancer (NSCLC) will be randomized to receive single agent pembrolizumab for up to
      35 treatments or standard of care (SOC) platinum-based chemotherapy (carboplatin + paclitaxel
      or carboplatin + pemetrexed for 4 to 6 21-day cycles). Participants in the platinum-based
      chemotherapy arms with non-squamous tumor histologies may receive pemetrexed maintenance
      therapy after the 4 to 6 cycles of chemotherapy. The primary study hypothesis is that
      pembrolizumab prolongs overall survival (OS) compared to SOC chemotherapy.
    

Eligibility criteria:

        Inclusion criteria:

          -  Histologically- or cytologically-confirmed diagnosis of advanced or metastatic NSCLC

          -  PD-L1 positive tumor

          -  Measureable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

          -  Life expectancy of at least 3 months

          -  No prior systemic chemotherapy for the treatment of the participant's advanced or
             metastatic disease (treatment with chemotherapy and/or radiation as part of
             neoadjuvant/adjuvant therapy is allowed as long as completed at least 6 months prior
             to diagnosis of advanced or metastatic disease)

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

          -  Adequate organ function

          -  No prior malignancy, with the exception of basal cell carcinoma of the skin,
             superficial bladder cancer, squamous cell carcinoma of the skin, or in situ cancer, or
             has undergone potentially curative therapy with no evidence of that disease recurrence
             for 5 years since initiation of that therapy

          -  Submission of formalin-fixed diagnostic tumor tissue (in the case of participants
             having received adjuvant systemic therapy, the tissue should be taken after completion
             of this therapy)

          -  Female participants of childbearing potential must have a negative urine or serum
             pregnancy test and must be willing to use two adequate barrier methods of
             contraception or a barrier method plus a hormonal method starting with the screening
             visit through 120 days after the last dose of pembrolizumab or 180 days after the last
             dose of chemotherapeutic agents used in the study

          -  Male participants with a female partner(s) of child-bearing potential must be willing
             to use two adequate barrier methods of contraception from screening through 120 days
             after the last dose of pembrolizumab or 180 days after the last dose of
             chemotherapeutic agents used in the study

        Exclusion criteria:

          -  Epidermal growth factor receptor (EGFR)-sensitizing mutation and/or is echinoderm
             microtubule-associated protein-like 4(EML4) gene/anaplastic lymphoma kinase (ALK) gene
             fusion positive

          -  Currently participating or has participated in a study of an investigational agent or
             using an investigational device within 4 weeks of the first dose of study therapy

          -  No tumor specimen evaluable for PD-L1 expression by the central study laboratory

          -  Squamous histology and received carboplatin in combination with paclitaxel in the
             adjuvant setting

          -  Is receiving systemic steroid therapy ≤3 days prior to the first dose of study therapy
             or receiving any other form of immunosuppressive medication with the exception of
             daily steroid replacement therapy

          -  The NSCLC can be treated with curative intent with either surgical resection and/or
             chemoradiation

          -  Expected to require any other form of systemic or localized antineoplastic therapy
             while on study

          -  Any prior systemic cytotoxic chemotherapy, biological therapy or major surgery within
             3 weeks of the first dose of study therapy; received lung radiation therapy >30 Gy
             within 6 months of the first dose of study therapy

          -  Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic
             T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other
             antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)

          -  Known central nervous system metastases and/or carcinomatous meningitis

          -  Active autoimmune disease that has required systemic treatment in the past 2 years

          -  Had allogeneic tissue/solid organ transplantation

          -  Interstitial lung disease or history of pneumonitis that has required oral or IV
             steroids

          -  Has received or will receive a live vaccine within 30 days prior to the first study
             therapy (seasonal flu vaccines that do not contain live vaccine are permitted)

          -  Active infection requiring intravenous systemic therapy

          -  Known history of human immunodeficiency virus (HIV)

          -  Known active Hepatitis B or C

          -  Regular user (including "recreational use") of any illicit drugs or had a recent
             history (within the last year) of substance abuse (including alcohol)

          -  Pregnant, breastfeeding, or expecting to conceive or father children within the
             projected duration of the study