Study of Pembrolizumab Versus Docetaxel in Participants Previously Treated for Non-Small Cell Lung Cancer (MK-3475-033/KEYNOTE-033)
Condition: Carcinoma, Non-Small-Cell Lung
MeSH terms: Carcinoma, Non-Small-Cell Lung
Intervention: Pembrolizumab; Docetaxel
Intervention description: Pembrolizumab administered IV at 2 mg/kg on Day 1 of each 21-day cycle for up to 35 doses (approximately 24 months).; Docetaxel administered IV at 75 mg/m^2 on Day 1 of each 21-day cycle as per the approved product label.
Intervention MeSH terms: Docetaxel; Pembrolizumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 425.0
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:

      The purpose of this study is to assess the efficacy of pembrolizumab (MK-3475) versus
      docetaxel in participants with non-small cell lung cancer (NSCLC) with programmed cell death
      ligand 1 (PD-L1) positive tumors who have experienced disease progression after
      platinum-containing systemic therapy. The primary hypotheses of this study are that
      pembrolizumab (MK-3475) prolongs overall survival (OS) and that pembrolizumab prolongs
      progression-free survival (PFS), compared to docetaxel in participants with PD-L1 positive
      tumors.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Chinese participants must be born, raised, and reside in China

          -  Has a histologically or cytologically confirmed diagnosis of stage IIIB/IV or
             recurrent NSCLC and have at least one measurable lesion as defined by RECIST 1.1

          -  Has a life expectancy of ≥3 months

          -  Has progression of disease (investigator determined) per RECIST 1.1 after treatment
             with at least two cycles of a platinum-containing doublet

          -  Has documentation of epidermal growth factor receptor (EGFR) mutation and anaplastic
             lymphoma kinase (ALK) translocation status

          -  Participants with an EGFR sensitizing mutation tumor will be excluded

          -  Has Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 within 10
             days prior to study start

          -  Has provided archival tumor tissue sample or newly obtained formalin fixed tumor
             tissue from a recent biopsy of a tumor lesion not previously irradiated

          -  Has a PD-L1 positive tumor as determined by immunohistochemistry at a central
             laboratory

          -  Has resolution of toxic effect(s) of the most recent prior chemotherapy to Grade 1 or
             less (except alopecia)

          -  Has recovered from the toxicity and/or complications of any recent major surgery or
             radiation therapy

          -  Females must not be pregnant (negative urine or serum human chorionic gonadotropin
             test within 72 hours prior to receiving the first dose of study medication)

          -  Female and male participants of reproductive potential must agree to use adequate
             contraception starting with the first dose of study therapy through 120 days after the
             last dose of pembrolizumab (MK-3475) or 180 days after the last dose of docetaxel

        Exclusion Criteria:

          -  Has received prior therapy with docetaxel for NSCLC

          -  Is 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 treatment

          -  Is receiving systemic steroid therapy within 3 days prior to the first dose of study
             treatment or receiving any other form of immunosuppressive

          -  Is expected to require any other form of systemic or localized antineoplastic therapy
             while on study including maintenance therapy with another agent for NSCLC or radiation
             therapy

          -  Has received prior systemic cytotoxic chemotherapy, antineoplastic biological therapy
             (e.g., cetuximab), any other agents used as systemic treatment for cancer, or major
             surgery within 3 weeks of the first dose of study treatment; received thoracic
             radiation therapy of > 30 Gray Units (Gy) within 6 months of the first dose of study
             treatment; received prior ALK-directed tyrosine kinase inhibitor therapy or completed
             palliative radiotherapy of 30 Gy or less within 7 days of the first dose of study
             treatment

          -  Has received prior therapy with an anti-programmed cell death 1 (anti-PD-1),
             anti-PD-L1, anti-PD-L2, with an agent directed to an agonist or antagonist T-cell
             check point receptor, or if the participant has previously participated in Merck
             sponsored clinical trials evaluating pembrolizumab (MK-3475)

          -  Has a known additional malignancy that is progressing or requires active treatment,
             with the exception of early stage cancers, treated with curative intent, basal cell
             carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer,
             or in situ breast cancer that has undergone potentially curative therapy

          -  Has known active central nervous system metastases and/or carcinomatous meningitis

          -  Has active autoimmune disease that has required systemic treatment in past 2 years

          -  Has had an allogeneic tissue/solid organ transplant

          -  Has a history of (non-infectious) pneumonitis that required steroids or current
             pneumonitis

          -  Has received or will receive a live vaccine within 30 days prior to the first
             administration of study medication

          -  Has an active infection requiring intravenous systemic therapy

          -  Has known history of Human Immunodeficiency Virus (HIV) (HIV ½ antibodies)

          -  Has known active Hepatitis B or C

          -  Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial

          -  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)

          -  Is pregnant or breastfeeding, or expecting to conceive or father children starting
             with the screening visit (Visit 1) through 120 days after the last dose of
             pembrolizumab (MK-3475) or 180 days after the last dose of docetaxel

          -  Requires treatment with a strong inhibitor of Cytochrome P450 3A4