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)

A Phase I Study of MK-3475 Alone in Subjects With Advanced Solid Tumors and in Combination With Platinum-Doublet Chemotherapy or Immunotherapy in Subjects With Advanced Non-Small Cell Lung Cancer/Extensive-Disease Small Cell Lung Cancer.

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.

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.