Study of Pembrolizumab Given With Ipilimumab or Placebo in Participants With Untreated Metastatic Non-Small Cell Lung Cancer (NSCLC) (MK-3475-598/KEYNOTE-598)
Condition: Carcinoma, Non-Small-Cell Lung
MeSH terms: Carcinoma, Non-Small-Cell Lung
Intervention: Pembrolizumab; Ipilimumab; Placebo
Intervention description: Administered as an intravenous (IV) infusion every 3 weeks (Q3W); Administered as an IV infusion every 6 weeks (Q6W); Normal saline solution administered as an IV infusion Q6W
Intervention MeSH terms: Pembrolizumab; Ipilimumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 568.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Programmed Cell Death Receptor 1 (PD-1); Programmed Cell Death Receptor Ligand 1 (PD-L1); Cytotoxic T-lymphocyte-associated protein 4 (CTLA4); PD1; PD-1; PDL1; PD-L1; CTLA4

Summary:

      The purpose of this study is to determine the efficacy of pembrolizumab given in combination
      with either ipilimumab or placebo as first-line treatment in participants with metastatic
      non-small cell lung cancer (NSCLC). The primary hypothesis of this study is that overall
      survival (OS) and/or progression-free survival (PFS) is prolonged in participants who receive
      pembrolizumab and ipilimumab compared to those who receive pembrolizumab and placebo.

      With Amendment 6 (effective date: 11-Dec-2020), active participants, investigator, and
      sponsor personnel or delegate(s) involved in the treatment administration or clinical
      evaluation of the participants will be unblinded. Participants will discontinue ipilimumab
      and placebo and participants who remain on treatment will receive open-label pembrolizumab
      only.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Has a histologically or cytologically confirmed diagnosis of Stage IV metastatic
             non-small cell lung cancer (NSCLC) (American Joint Committee on Cancer version 8)

          -  Has measurable disease per Response Evaluation Criteria in Solid Tumors Version 1.1
             (RECIST 1.1) as determined by investigator

          -  Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  Has a life expectancy of at least 3 months

          -  Has provided archival tumor tissue sample or newly obtained core or excisional biopsy
             of a tumor lesion not previously irradiated

          -  Female participants of childbearing potential must have a negative serum pregnancy
             test within 72 hours prior to receiving the first dose of study therapy

          -  Female participants of reproductive potential must agree to use contraception starting
             from the first dose of study medication, throughout the study period, and for up to
             120 days after the last dose of study medication

        Exclusion Criteria:

          -  Has received prior systemic chemotherapy/other targeted or biological antineoplastic
             therapy treatment for their Stage IV metastatic NSCLC

          -  Has a tumor that harbors an epidermal growth factor receptor (EGFR)-sensitizing
             (activating) mutation or an anaplastic lymphoma kinase (ALK) translocation

          -  Is currently participating in or has participated in a trial of an investigational
             agent or has used an investigational device within 4 weeks prior to the first dose of
             study therapy

          -  Has received prior therapy with an anti-Programmed Cell Death Receptor 1 (PD-1),
             anti-Programmed Cell Death Receptor Ligand 1 (anti-PD-L1), or anti- Programmed Cell
             Death Receptor Ligand 2 (PD-L2) agent or with an agent directed to another stimulatory
             or co-inhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein 4
             [CTLA-4], OX-40, CD137)

          -  Has received prior radiotherapy within 2 weeks of start of study therapy or received
             lung radiation therapy of >30 Gray (Gy) within 6 months of the first dose of study
             therapy

          -  Has recovered from all radiation-related toxicities, does not require corticosteroids,
             and has not had radiation pneumonitis

          -  Is receiving systemic steroid therapy ≤7 days prior to the first dose of study therapy
             or receiving any other form of immunosuppressive medication

          -  Has a known additional malignancy that is progressing or has required active treatment
             within the past 3 years with the exception of curatively treated basal cell carcinoma
             of the skin, squamous cell carcinoma of the skin and/or curatively resected in situ
             cancers

          -  Has known untreated central nervous system (CNS) metastases and/or carcinomatous
             meningitis

          -  Has an active autoimmune disease that has required systemic treatment in past 2 years
             (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive
             drugs)

          -  Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
             (i.e., doses exceeding 10 mg daily of prednisone equivalent) or any other form of
             immunosuppressive therapy within 7 days prior the first dose of study therapy

          -  Has a history of (non-infectious) pneumonitis that required systemic steroids or
             current pneumonitis/interstitial lung disease

          -  Has had an allogeneic tissue/solid organ transplant

          -  Has received a live vaccine within 30 days prior to the first dose of study therapy

          -  Has an active infection requiring systemic therapy

          -  Has a known history of human immunodeficiency virus (HIV) infection

          -  Has a known history of hepatitis B or known active hepatitis C virus infection

          -  Has a known history of active tuberculosis

          -  Has known psychiatric or substance abuse disorders that would interfere with
             cooperating with the requirements of the trial

          -  Is a regular user of any illicit drugs or had a recent history of substance abuse

          -  Is pregnant or breast feeding or expecting to conceive starting from the first dose of
             study medication, throughout the study period, and for up to 120 days after the last
             dose of study medication

          -  Has severe hypersensitivity to pembrolizumab and/or any of its excipients and/or to
             ipilimumab and/or any of its excipients

          -  Has a c-ros oncogene 1 (ROS1) mutation