A Study of Pembrolizumab (MK-3475) in Combination With Etoposide/Platinum (Cisplatin or Carboplatin) for Participants With Extensive Stage Small Cell Lung Cancer (MK-3475-604/KEYNOTE-604)
Condition: Small Cell Lung Cancer (SCLC)
MeSH terms: Lung Neoplasms; Small Cell Lung Carcinoma
Intervention: Pembrolizumab; Normal saline solution; Carboplatin; Cisplatin; Etoposide
Intervention description: IV infusion on Day 1 of each cycle prior to chemotherapy; IV infusion on Day 1 of each cycle prior to chemotherapy; IV infusion on Day 1 of each cycle; IV infusion on Day 1 of each cycle; IV infusion on Days 1, 2 and 3 of each cycle
Intervention MeSH terms: Carboplatin; Pembrolizumab; Etoposide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 453.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Extensive stage small cell lung cancer (ES-SCLC); Programmed Cell Death-1 (PD1, PD-1); Programmed Cell Death Ligand 1 (PDL1, PD-L1); Programmed Cell Death Ligand 2 (PDL2, PD-L2)

Summary:

      The purpose of this study is to assess the safety and efficacy of pembrolizumab plus standard
      of care (SOC) chemotherapy (etoposide/platinum [EP]) in participants with newly diagnosed
      extensive stage small cell lung cancer (ES-SCLC) who have not previously received systemic
      therapy for this malignancy.

      The primary study hypotheses are that pembrolizumab+EP prolongs Progression-free Survival
      (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by blinded
      independent central review (BICR) and Overall Survival (OS) compared with placebo+EP in adult
      participants with ES-SCLC. In this study, RECIST 1.1 has been modified to follow a maximum of
      10 target lesions and a maximum of 5 target lesions per organ.

      With protocol Amendment 07 (03-Oct-2018), the outcome measure of "Change from Baseline at
      Weeks 12 and 24 in European Organization for Research and Treatment of Cancer (EORTC) Quality
      of Life Questionnaire Core 30 (QLQ-C30) Global Health Status/Quality of Life Scale" was
      replaced with a single time point analysis at Week 18.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Has a documented new diagnosis of SCLC by histology or cytology from brushing,
             washing, or needle aspiration of a defined lesion. Participants who do not have
             histology samples (defined as core or excisional biopsy, or resections) will need to
             undergo a new biopsy to provide a tissue sample.

          -  Has extensive-stage disease defined as Stage IV (T any, N any, M 1a/b) by the American
             Joint Committee on Cancer (AJCC), Seventh Edition

          -  Has ≥1 lesion that meets the criteria for measurable, as defined by RECIST 1.1, and is
             appropriate for selection as a target lesion, as determined by local site
             investigator/radiology assessment

          -  Has provided archival tumor tissue sample or newly obtained core or excisional biopsy
             of a tumor lesion not previously irradiated

          -  Has Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

          -  Has a life expectancy of ≥3 months

          -  Has adequate organ function

          -  Female and male participants of childbearing potential must be willing to use an
             adequate method of contraception, starting with the first dose of study treatment
             through 120 days after the last dose of study treatment and up to 180 days after last
             dose of chemotherapeutic agents

        Exclusion Criteria:

          -  Has received prior systemic therapy for the treatment of SCLC

          -  Is currently participating and receiving study treatment or has participated in a
             study of an investigational agent and received study treatment or used an
             investigational device within 4 weeks of the first dose of treatment for another
             health-related problem

          -  Is expected to require any other form of antineoplastic therapy for SCLC, including
             radiation therapy, while on study. (Prophylactic cranial irradiation will be possible
             for those participants with stable disease or better at the completion of the 4 cycles
             of chemotherapy with or without pembrolizumab.)

          -  Has known central nervous system (ie, brain and/or spinal cord) metastases and/or
             carcinomatous meningitis. Participants with brain metastases may participate only if
             they satisfy all of the following:

          -  Has completed treatment (eg, whole brain radiation treatment [WBRT], stereotactic
             radiosurgery, or equivalent) ≥14 days prior to the first dose of study treatment,

          -  Has no evidence of new or enlarging brain metastases confirmed by post-treatment
             repeat brain imaging performed ≥3 weeks after pre-treatment brain imaging, and

          -  Is neurologically stable without the need for steroids for ≥7 days before first dose
             of study treatment.

          -  Has had major surgery within 3 weeks prior to receiving the first dose of study
             treatment or has not recovered adequately from toxicity and/or complications from an
             intervention prior to receiving the first dose of study treatment.

          -  Has a history of (non-infectious) pneumonitis that required steroids or has current
             pneumonitis

          -  Has a known history of interstitial lung disease

          -  Has a known additional malignancy that is progressing or requires active treatment.
             Exceptions include early stage cancers (carcinoma in situ or Stage 1) 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 active autoimmune disease that has required systemic treatment in the past 2
             years. Replacement therapy is not considered a form of systemic treatment.

          -  Has a known history of, or active, neurologic paraneoplastic syndrome

          -  Has clinically active diverticulitis, intra-abdominal abscess, gastrointestinal
             obstruction, and/or abdominal carcinomatosis

          -  Has a history of a severe hypersensitivity reaction to treatment with another
             monoclonal antibody

          -  Is taking chronic systemic steroids (in doses exceeding 10 mg daily of prednisone
             equivalent) within 7 days prior to the first dose of study treatment

          -  Has a diagnosis of immunodeficiency or is receiving any form of immunosuppressive
             therapy within 7 days prior to the first dose of study treatment

          -  Has received a live vaccine within 30 days prior to the first dose of study treatment

          -  Has received prior therapy with an anti-programmed cell death protein-1 (anti-PD-1),
             anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-programmed cell death-ligand
             2 (anti-PD-L2) agent or with an agent directed to another co-inhibitory T-cell
             receptor (i.e., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], tumor necrosis
             factor receptor superfamily member 9 [TNFRSF9, OX-40, CD137]) or has previously
             participated in a Merck pembrolizumab (MK-3475) clinical trial

          -  Has severe hypersensitivity (Grade ≥3) to pembrolizumab and/or any of its excipients

          -  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 TB (Bacillus Tuberculosis)

          -  Has symptomatic ascites or pleural effusion. A participant who is clinically stable
             following treatment for these conditions (including therapeutic thoraco- or
             paracentesis) is eligible.

          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the study starting with the screening visit through 120 days
             after the last dose of study treatment through and up to 180 days after last dose of
             chemotherapeutic agents