Study of MK-3475 (Lambrolizumab) in Participants With Progressive Locally Advanced or Metastatic Carcinoma, Melanoma, or Non-small Cell Lung Carcinoma (P07990/MK-3475-001 AM7)

• Number of participants experiencing dose-limiting toxicities (DLTs) [ Time Frame: Cycle 1 (28 days) ] [ Designated as safety issue: Yes ]
• Number of participants experiencing clinical and laboratory adverse events (AEs) [ Time Frame: First dose to 30 days post last dose ] [ Designated as safety issue: Yes ]
• Number of all study participants who demonstrate a response rate (RR) [ Time Frame: Weeks 12 & 24 ] [ Designated as safety issue: No ]
• Number of MEL participants who demonstrated a response rate (RR) and/or disease control rate (DCR) [ Time Frame: Weeks 12 & 24 ] [ Designated as safety issue: No ]
• Number of NSCLC participants who demonstrated a response rate (RR) [ Time Frame: Week 9 and Week 18 ] [ Designated as safety issue: No ]
• Change from Baseline in candidate biomarker expression levels in MELS and NSCLC participants [ Time Frame: Week 12 and Week 24 (MEL), Week 9 and Week 18 (NSCLC) ] [ Designated as safety issue: No ]

• Number of participants experiencing dose-limiting toxicities. [ Time Frame: Cycle 1 (28 days) ] [ Designated as safety issue: Yes ]
• Number of participants experiencing clinical and laboratory adverse events (AEs). [ Time Frame: First dose to 30 days post last dose ] [ Designated as safety issue: Yes ]

• The area under the curve (AUC) of plasma concentration of drug against time after administration of lambrolizumab (Part A) [ Time Frame: Pre-dose, 30 minutes, 6, 24, and 48 hours post-dose, and on Days 8, 15, 22, and 29 of Cycle 1; pre- and post-dose on Day 1 of every other subsequent 14-day cycle up to 12 months ] [ Designated as safety issue: No ]
• Maximum concentration (Cmax) after first dose interval of lambrolizumab [ Time Frame: Part A: over 48 hours in Cycle 1 and on Day 1 of every other subsequent 14-day cycle for up to 12 months. Parts B, C, D, E, and F: Cycles 1, 3, and 7 and then every 12 weeks for the first 12 months and every 6 months after that for up to 2 years. ] [ Designated as safety issue: No ]
• Time at which maximum concentration (Tmax) occurs for lambrolizumab (Part A) [ Time Frame: Pre-dose, 30 minutes, 6, 24, and 48 hours post-dose, and on Days 8, 15, 22, and 29 of Cycle 1; pre- and post-dose on Day 1 of every other subsequent 14-day cycle up to 12 months ] [ Designated as safety issue: No ]
• Lowest plasma concentration (C[trough]) of lambrolizumab [ Time Frame: Part A: over 48 hours in Cycle 1 and on Day 1 of every other subsequent 14-day cycle for up to 12 months. Parts B, C, D, E, and F: Cycles 1, 3, and 7 and then every 12 weeks for the first 12 months and every 6 months after that for up to 2 years. ] [ Designated as safety issue: No ]
• Terminal half-life (t1/2) of lambrolizumab (Parts B, C, D, E and F) [ Time Frame: Pre-dose, 30 minutes, 6, 24, and 48 hours post-dose, and on Days 8, 15, 22, and 29 of Cycle 1; pre- and post-dose on Day 1 of every other subsequent 14-day cycle up to 12 months ] [ Designated as safety issue: No ]
• Progression free survival (PFS) in MEL and NSCLC participants [ Time Frame: From first documented response up to 2 years ] [ Designated as safety issue: No ]
• Overall survival (OS) in MEL and NSCLC participants [ Time Frame: From first dose of study drug until death or lost to follow-up (up to 2 years) ] [ Designated as safety issue: No ]
• Duration of response (DR) in MEL and NSCLC participants [ Time Frame: From first documented response up to 2 years ] [ Designated as safety issue: No ]

• The area under the curve (AUC) of plasma concentration of drug against time after administration of MK-3475. [ Time Frame: Pre-dose, 30 minutes, 6, 24, and 48 hours post-dose, and on Days 8, 15, 22, and 29 of Cycle 1; pre- and post-dose on Days 1 and 14 of every other subsequent 14-day cycle up to 12 months ] [ Designated as safety issue: No ]
• Maximum concentration (Cmax) after first dose interval of MK-3475. [ Time Frame: Pre-dose, 30 minutes, 6, 24, and 48 hours post-dose, and on Days 8, 15, 22, and 29 of Cycle 1; pre- and post-dose on Days 1 and 14 of every other subsequent 14-day cycle up to 12 months ] [ Designated as safety issue: No ]
• Time at which maximum concentration (Tmax) occurs for MK-3475 [ Time Frame: Pre-dose, 30 minutes, 6, 24, and 48 hours post-dose, and on Days 8, 15, 22, and 29 of Cycle 1; pre- and post-dose on Days 1 and 14 of every other subsequent 14-day cycle up to 12 months ] [ Designated as safety issue: No ]
• Lowest plasma concentration (C[trough]) of MK-3475 [ Time Frame: Pre-dose, 30 minutes, 6, 24, and 48 hours post-dose, and on Days 8, 15, 22, and 29 of Cycle 1; pre- and post-dose on Days 1 and 14 of every other subsequent 14-day cycle up to 12 months ] [ Designated as safety issue: No ]

This study will be done in 5 parts. In Part A the dose of intravenous (IV) lambrolizumab will be escalated to find the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) for participants with a histologically or cytologically confirmed diagnosis of any type of carcinoma or melanoma (MEL). Part B of the study will explore the safety, tolerability, and efficacy of the drug in participants with advanced or metastatic MEL and compare every 2 week to every 3 week dosing. Part C of the study will explore the safety, tolerability, and efficacy of the drug in participants with non-small cell lung carcinoma (NSCLC) that is locally advanced or metastatic. Part D of the study will explore the low and high doses of study drug identified in Parts A and B in participants with advanced or metastatic MEL. Part E (closed with Amendment 7) will explore low, medium, and high doses of study drug in combination with standard chemotherapy in participants with locally advanced or metastatic NSCLC. Part F will explore low and high doses of study drug in treatment-naive and previously-treated participants with NSCLC with programmed cell death 1 ligand (PD-L1) gene expression. In Parts D and F and some of Part B participants will be randomized to one dose level.

• Drug: lambrolizumab 1 mg/kg
  IV infusion over 30 minutes on Day 1 of each cycle, at dose of 1 mg/kg
  Other Names:

  • SCH 900475
  • MK-3475
• Drug: lambrolizumab 3 mg/kg
  IV infusion over 30 minutes on Day 1 of each cycle, at dose of 3 mg/kg
  Other Names:

  • SCH 900475
  • MK-3475
• Drug: lambrolizumab 10 mg/kg
  IV infusion over 30 minutes on Day 1 of each cycle (every 2 or 3 weeks depending on study arm) at a dose of 10 mg/kg.
  Other Names:

  • SCH 900475
  • MK-3475
• Drug: lambrolizumab MEL
  IV infusion over 30 minutes on Day 1 of each cycle
  Other Names:

  • SCH 900475
  • MK-3475
• Drug: lambrolizumab NSCLC
  IV infusion over 30 minutes on Day 1 of each cycle
  Other Names:

  • SCH 900475
  • MK-3475
• Drug: lambrolizumab MEL Low Dose
  IV infusion over 30 minutes every 3 weeks at dose determined during dose escalation
  Other Names:

  • SCH 900475
  • MK-3475
• Drug: lambrolizumab MEL High Dose
  IV infusion over 30 minutes every 3 weeks at dose determined during dose escalation
  Other Names:

  • SCH 900475
  • MK-3475
• Drug: lambrolizumab NSCLC Low Dose
  IV infusion over 30 minutes every 3 weeks at dose determined during dose escalation
  Other Names:

  • SCH 900475
  • MK-3475
• Drug: lambrolizumab NSCLC High Dose
  IV infusion over 30 minutes every 3 weeks at dose determined during dose escalation
  Other Names:

  • SCH 900475
  • MK-3475
• Drug: lambrolizumab NSCLC Medium Dose
  IV infusion over 30 minutes every 3 weeks at dose determined during dose escalation
  Other Names:

  • SCH 900475
  • MK-3475

• Experimental: Part A: lambrolizumab 1 mg/kg
  Intervention: Drug: lambrolizumab 1 mg/kg
• Experimental: Part A: lambrolizumab 3 mg/kg
  Intervention: Drug: lambrolizumab 3 mg/kg
• Experimental: Part A: lambrolizumab 10 mg/kg
  Intervention: Drug: lambrolizumab 10 mg/kg
• Experimental: Part B: lambrolizumab MEL
  Intervention: Drug: lambrolizumab MEL
• Experimental: Part C: lambrolizumab NSCLC
  Intervention: Drug: lambrolizumab NSCLC
• Experimental: Part D: lambrolizumab MEL Low Dose
  Intervention: Drug: lambrolizumab MEL Low Dose
• Experimental: Part D: lambrolizumab MEL High Dose
  Intervention: Drug: lambrolizumab MEL High Dose
• Experimental: Part E: lambrolizumab NSCLC Low Dose
  Arm closed with Amendment 7
  Intervention: Drug: lambrolizumab NSCLC Low Dose
• Experimental: Part E: lambrolizumab NSCLC Medium Dose
  Arm closed with Amendment 7
  Interventions:

  • Drug: lambrolizumab NSCLC High Dose
  • Drug: lambrolizumab NSCLC Medium Dose
• Experimental: Part E: lambrolizumab NSCLC High Dose
  Arm closed with Amendment 7
  Intervention: Drug: lambrolizumab NSCLC Low Dose
• Experimental: Part F: lambrolizumab NSCLC PD-L1 Low Dose
  Intervention: Drug: lambrolizumab NSCLC High Dose
• Experimental: Part F: lambrolizumab NSCLC PD-L1 High Dose
  Intervention: Drug: lambrolizumab NSCLC Medium Dose

Inclusion criteria

• In Part A: Histological or cytological diagnosis of MEL or any type of carcinoma, progressive metastatic disease, or progressive locally advanced disease not amenable to local therapy. In Parts B and D of the study, histological or cytological diagnoses of metastatic MEL with progressive locally advanced or metastatic disease. In Parts C and F, histological or cytological diagnosis of NSCLC.
• Failure of established standard medical anti-cancer therapies for a given tumor type or intolerance to such therapy.
• In Parts B, C, D, or F of the study, MEL or NSCLC must be measurable by imaging.
• In Part F of the study, NSCLC with PD-L1 gene expression.
• Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
• Adequate organ function.

Exclusion criteria

• Chemotherapy, radioactive, or biological cancer therapy within 4 weeks prior to the first dose of study therapy, or not recovered to Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or better from the adverse events caused by therapy administered more than 4 weeks prior to first dose.
• Participation in a study of an investigational agent or using an investigational device within 30 days of administration of lambrolizumab.
• Other form(s) of antineoplastic therapy anticipated during the period of the study.
• History of pneumonitis or interstitial lung disease.
• Medical condition that requires chronic systemic steroid therapy, or on any other form of immunosuppressive medication.
• History of acute diverticulitis, intra-abdominal abscess, GI obstruction, abdominal carcinomatosis.
• History of a hematologic malignancy, primary brain tumor, sarcoma, or another primary solid tumor, unless no evidence of that disease for 5 years.
• Active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Previous severe hypersensitivity reaction to another monoclonal antibody (mAb).
• Active autoimmune disease or a documented history of autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents, except vitiligo or resolved childhood asthma/atopy.
• Prior therapy with another anti-programmed cell death (PD)-1 agent or previously enrolled in any lambrolizumab trial.
• Active infection requiring therapy.
• Positive for Human Immunodeficiency Virus (HIV), Hepatitis B (Hepatitis B Surface Antigen [HBsAg] reactive), or Hepatitis C virus (Hepatitis C Virus Ribonucleic Acid [HCV RNA] (qualitative) is detected).
• Regular use of illicit drugs or a recent history (within the last year) of substance abuse (including alcohol).
• Symptomatic ascites or pleural effusion.
• Participant is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study.