Study of Pembrolizumab (MK-3475) Monotherapy in Advanced Solid Tumors and Pembrolizumab Combination Therapy in Advanced Non-small Cell Lung Cancer/ Extensive-disease Small Cell Lung Cancer (MK-3475-011/KEYNOTE-011)
Condition: Solid Tumor; Non-small Cell Lung Cancer; Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Small Cell Lung Carcinoma
Intervention: Pembrolizumab 2 mg/kg; Pembrolizumab 10 mg/kg; Pembrolizumab 200 mg; Cisplatin 75 mg/m^2; Pemetrexed 500 mg/m^2; Carboplatin AUC 5 mg/mL/min; Carboplatin AUC 6 mg/mL/min; Paclitaxel 200 mg/m^2; Nab-paclitaxel 100 mg/m^2; Ipilimumab 1 mg/kg; Etoposide 100 mg/m^2; G-CSF (pegfilgrastim) 3.6 mg
Intervention description: Administered as an intravenous (IV) infusion on Day 1 of Cycle 1 (28 days), Cycle 2 (14 days), and Cycle 3 (14 days); Administered as an IV infusion on Day 1 of Cycle 1 (28 days), Cycle 2 (14 days), and Cycle 3 (14 days); Administered as an IV infusion on Day 1 of each 21-day cycle; Administered as an IV infusion on Day 1 of each 21-day cycle; Administered as an IV infusion on Day 1 of each 21-day cycle; Administered as an IV infusion on Day 1 of each 21-day cycle; Administered as an IV infusion on Day 1 of each 21-day cycle; Administered as an IV infusion on Day 1 of each 21-day cycle; Administered as an IV infusion on Days 1, 8, and 15 of each 21-day cycle; Administered as an IV infusion on Day 1 of every other 21-day cycle (every 42 days); Administered as an IV infusion on Days 1, 2, and 3 of each 21-day cycle; Administered as a subcutaneous injection on Day 4 of Cycle 1
Intervention MeSH terms: Paclitaxel; Etoposide; Albumin-Bound Paclitaxel; Carboplatin; Pembrolizumab; Pemetrexed; Ipilimumab
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 57.0
Sex: All
Minimum age: 20 Years
Healthy volunteers: No

Summary:

      This study using pembrolizumab (MK-3475) will be done in 5 parts. In Part A, successive
      participant cohorts with advanced solid tumors will receive pembrolizumab to assess the
      safety and tolerability of monotherapy. In Parts B, C, and D, participants with advanced
      non-small cell lung cancer (NSCLC) will receive pembrolizumab in combination with either
      cisplatin/pemetrexed or carboplatin/pemetrexed (Part B); with either carboplatin/paclitaxel
      or carboplatin/nab-paclitaxel (Part C); or with ipilimumab (Part D) by non-random assignment
      to assess the safety and tolerability of the combination therapy. In Part E, participants
      with untreated Extensive-disease (ED) Small Cell Lung Cancer (SCLC) will receive
      pembrolizumab in combination with either cisplatin/etoposide, carboplatin/etoposide, or
      cisplatin/etoposide with prophylactic use of granulocyte colony-stimulating factor (lasting
      G-CSF [pegfilgrastim]) by non-random assignment to assess the safety and tolerability of the
      combination therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  In Part A: has a histological or cytological diagnosis of solid tumor, progressive
             metastatic disease, or progressive locally advanced disease not amenable to local
             therapy

          -  In Part B, C, and D: has a histologically- or cytologically-confirmed diagnosis of
             NSCLC (Stage IIIB/IV) and are naïve to systemic therapy

          -  In Part C: has a histologically- or cytologically-confirmed diagnosis of squamous
             cancer

          -  In Part E: has a histologically- or cytologically-confirmed diagnosis of SCLC (ED
             stage) and are naïve to systemic therapy

          -  Has Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

          -  Has adequate organ function

          -  Female participants of reproductive potential must not be pregnant (negative urine or
             serum human chorionic gonadotropin test within 72 hours of study start)

          -  Female and male participants of reproductive potential must agree to use adequate
             contraception throughout the study period and for up to 120 days after the last dose
             of study therapy and for up to 180 days after the last dose of chemotherapeutic agents

        Exclusion criteria:

          -  Has had cancer therapy within 2 weeks (Part E) or 4 weeks (Parts A, B, C, and D) prior
             to the first dose of study therapy, or not recovered from the adverse events of agents
             administered more than 4 weeks prior to the first dose of study therapy.

               -  Part A: Chemotherapy, radiation therapy, biological therapy or kinase inhibitors

               -  Parts B, C, D and E: Radiation therapy

          -  For Part B: has a histological diagnosis of squamous cancer

          -  Is currently participating or has participated in a study with an investigational
             agent or using an investigational device within 30 days of first dose of study therapy

          -  Is expected to require any other form of antineoplastic therapy while on study

          -  Is on chronic systemic steroid therapy within two weeks prior to the first dose of
             trial treatment or on any other form of immunosuppressive medication

          -  For Part C: Has pre-existing peripheral neuropathy that is ≥ Grade 2 by Common
             Terminology Criteria for Adverse Events version 4 criteria

          -  Has interstitial lung disease detected by chest computed tomography (CT), or a history
             of pneumonitis that required oral or intravenous glucocorticoids to assist with
             management. Lymphangitic spread of the NSCLC is not exclusionary.