Study of Pembrolizumab (MK-3475) Compared to Platinum-Based Chemotherapies in Participants With Metastatic Non-Small Cell Lung Cancer (MK-3475-024/KEYNOTE-024)
Condition: Non-Small Cell Lung Carcinoma
MeSH terms: Carcinoma, Non-Small-Cell Lung
Intervention: Pembrolizumab; Paclitaxel; Carboplatin; Pemetrexed; Cisplatin; Gemcitabine
Intervention description: Pembrolizumab IV solution; Paclitaxel IV solution; Carboplatin IV solution; Pemetrexed Lyophilized Powder for Infusion; Cisplatin IV solution; Gemcitabine Lyophilized Powder for Infusion
Intervention MeSH terms: Paclitaxel; Carboplatin; Gemcitabine; Pembrolizumab; Pemetrexed
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 305.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Programmed cell death-1 (PD-1); Programmed cell death 1 (PD1); Programmed death-ligand 1 (PDL1); PD-L1

Summary:

      This is a study to assess the efficacy and safety of pembrolizumab (MK-3475/SCH 900475)
      compared to standard of care (SOC) platinum-based chemotherapies in the treatment of
      participants with previously untreated stage IV, programmed cell death ligand 1 (PD-L1)
      strong expressing Non-Small Cell Lung Cancer (NSCLC). The primary hypothesis of this study is
      that participants with PD-L1 strong NSCLC will have a longer Progression Free Survival (PFS),
      as assessed by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) when
      treated with pembrolizumab than when treated with SOC platinum-based chemotherapies.

      With Amendment 09 (20 December 2017), once participants have achieved the study objective or
      the study has ended, participants will be discontinued from this study and enrolled in an
      extension study to continue protocol-defined assessments and treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histological or cytological diagnosis of Stage IV NSCLC lacking epidermal growth
             factor receptor (EGFR)-sensitizing mutation and/or anaplastic lymphoma kinase (ALK)
             translocation, and received no prior systemic chemotherapy treatment for their
             metastatic NSCLC

          -  At least one radiographically measurable lesion per RECIST 1.1

          -  Life expectancy of at least 3 months

          -  Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
             Performance Status

          -  Adequate organ function

          -  No history of prior malignancy, with the exception of basal cell carcinoma of the
             skin, superficial bladder cancer, squamous cell carcinoma of the skin, or in situ
             cervical cancer, or has undergone potentially curative therapy with no evidence of
             that disease recurrence for 5 years since initiation of that therapy

          -  Provided newly obtained formalin fixed tumor tissue from a biopsy of a tumor at the
             time of or AFTER the diagnosis of metastatic disease has been made AND from a site not
             previously irradiated

          -  PD-L1 strong expressing tumor as determined by immunohistochemistry (IHC) at a central
             laboratory

          -  Female participants must have a negative pregnancy test at screening if of
             childbearing potential or be of non-childbearing potential

          -  Female participants of childbearing potential and male partners with female partners
             of childbearing potential must agree to use 2 adequate barrier methods of
             contraception during the study and for 120 days after last dose of study drug and up
             to 180 days after last dose of chemotherapy

        Exclusion Criteria:

          -  EGFR sensitizing mutation and/or ALK translocation

          -  Has received systemic therapy for the treatment of their stage IV NSCLC. Completion of
             treatment with chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy
             is allowed as long as therapy was completed at least 6 months prior to the diagnosis
             of metastatic disease.

          -  Currently participating or has participated in a study of an investigational agent or
             using an investigational device within 4 weeks of first dose of study drug

          -  Tumor specimen is not evaluable for PD-L1 expression by the central laboratory

          -  Receiving systemic steroid therapy < 3 days prior to first dose of study drug or
             receiving any other form of immunosuppressive medication

          -  Expected to require any other form of systemic or localized antineoplastic therapy
             during the study

          -  Received prior systemic cytotoxic chemotherapy, biological therapy, major surgery
             within 3 weeks of first dose of study drug; received thoracic radiation therapy of >
             30 gray (Gy) within 6 months of first dose of study drug

          -  Received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1),
             anti-PD-L1, anti-programmed cell death-ligand 2 (anti-PD-L2), anti-CD137 (4-1BB
             ligand, a member of the Tumor Necrosis Factor Receptor [TNFR] family), or
             anti-Cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4) antibody (including
             ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation
             or checkpoint pathways)

          -  Has untreated central nervous system (CNS) metastases and/or carcinomatous meningitis

          -  Active autoimmune disease that has required systemic treatment in past 2 years

          -  Allogenic tissue/solid organ transplant

          -  Interstitial lung disease or pneumonitis that has required oral or IV steroids

          -  Received or will receive a live vaccine within 30 days prior to first dose of study
             drug

          -  Active infection requiring IV systemic therapy

          -  Known history of human immunodeficiency virus (HIV)

          -  Known active tuberculosis, or hepatitis B or C

          -  Known psychiatric or substance abuse disorders that would interfere with cooperation
             with the requirements of the study

          -  Is, at the time of signing informed consent, a regular user (including "recreational
             use") of any illicit drugs or had a recent history (within the last year) of substance
             abuse (including alcohol)

          -  Pregnant or breastfeeding, or expecting to conceive or father children during the
             study and through 120 days after last dose of pembrolizumab or 180 days after last
             dose of SOC chemotherapy

          -  Immediate family member who is investigational site or sponsor staff directly involved
             with this study