Study of Pembrolizumab (MK-3475) vs Placebo for Participants With Non-small Cell Lung Cancer After Resection With or Without Standard Adjuvant Therapy (MK-3475-091/KEYNOTE-091)
Condition: Non-small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Pembrolizumab; Placebo
Intervention description: IV infusion; IV infusion
Intervention MeSH terms: Pembrolizumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 1177.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Non-small cell lung cancer (NSCLC); Programmed Cell Death Receptor 1 (PD-1); Programmed Cell Death Receptor Ligand 1 (PD-L1); Programmed Cell Death Receptor Ligand (PDL)

Summary:

      In this study, participants with Stage IB/II-IIIA non-small cell lung cancer (NSCLC) who have
      undergone surgical resection (lobectomy or pneumonectomy) with or without adjuvant
      chemotherapy will be treated with pembrolizumab or placebo. The primary study hypothesis is
      that pembrolizumab will provide improved disease-free survival (DFS) versus placebo.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Pathological diagnosis of NSCLC confirmed at surgery, any histology. Participants with
             two synchronous primary non-small cell lung cancers are excluded from the study

          -  Union for International Cancer Control (UICC) v7 Stage IB with T ≥ 4 cm, II-IIIA NSCLC
             after complete surgical resection with resection margins proved microscopically free
             of disease (R0). Carcinoma in situ can be present at the bronchial margin

          -  Available tumor sample obtained at surgical resection for programmed cell death
             ligand-1 (PD-L1) Immunohistochemistry (IHC) expression assessment

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1

          -  Adequate organ function performed within 10 days of treatment initiation

          -  Female participants of childbearing potential must have a negative urine or serum
             pregnancy test at screening (within 72 hours of first infusion of study medication).
             If the urine test cannot be confirmed as negative, a serum pregnancy test will be
             required. The serum pregnancy test must be negative for the participant to be eligible

          -  Female participants of childbearing potential must be willing to use 2 methods of
             birth control or be surgically sterile, or abstain from heterosexual activity starting
             with the first infusion of study treatment through 120 days after the last infusion of
             study treatment

          -  Female participants who are breast feeding must discontinue nursing prior to the first
             infusion of study medication and until 120 days after the last infusion study
             treatment

          -  Male participants must agree to use an adequate method of contraception starting with
             the first infusion of study treatment through 120 days after the last infusion of
             study treatment

          -  Absence of severe comorbidities that in the opinion of the Investigator might hamper
             the participation to the study and/or the treatment administration

          -  No prior or planned neo-adjuvant or adjuvant radiotherapy and/or neo-adjuvant
             chemotherapy for the current malignancy is allowed

        Exclusion Criteria:

          -  Evidence of disease at clinical examination and/or baseline radiological assessment as
             documented by contrast enhanced chest/upper abdomen CT scan, brain CT/MRI and clinical
             examination

          -  More than 4 cycles of adjuvant therapy

          -  Prior treatment with anti-programmed cell death (anti-PD)-1, anti-PD ligand-1/2,
             anti-CD137, or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) modulators or any
             other immune-modulating agents

          -  Live vaccine within 30 days prior to the first infusion of study treatment

          -  Current participation or treatment with an investigational agent or use of an
             investigational device within 4 weeks of the first infusion of study treatment

          -  History of Human Immunodeficiency Virus (HIV) (known HIV 1/2 antibodies positive). No
             known active Hepatitis B or C

          -  Chronic use of immunosuppressive agents and/or systemic corticosteroids or any use in
             the last 3 days prior to the first infusion of study treatment

          -  History of interstitial lung disease or (non-infectious) pneumonitis that required
             oral or IV steroids (other than COPD exacerbation) or current pneumonitis

          -  Active autoimmune disease that has required systemic treatment in past 2 years

          -  History of a hematologic or primary solid tumor malignancy, unless in remission for at
             least 5 years with the exception of pT1-2 prostatic cancer Gleason score < 6,
             superficial bladder cancer, non melanomatous skin cancer or carcinoma in situ of the
             cervix

          -  Previous allogeneic tissue/solid organ transplant

          -  Active infection requiring therapy

          -  Surgery- or chemotherapy-related toxicity (non-hematological) not resolved to Grade 1
             with the exception of alopecia, fatigue, neuropathy and lack of appetite /nausea

          -  Pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial, starting with the screening visit through 120 days
             after the last infusion of study treatment

          -  Participant will not be eligible if the participant is or has an immediate family
             member (e.g., spouse, parent/legal guardian, sibling or child) who is investigational
             site or Sponsor staff directly involved with this trial, unless prospective site
             Review Board approval is given allowing exception to this criterion for a specific
             participant