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

Brief Summary

Official Title: “Phase I Study of Single Agent MK-3475 in Patients With Progressive Locally Advanced or Metastatic Carcinoma, Melanoma, and Non-Small Cell Lung Carcinoma”

This study will be done in 6 parts. In Part A the dose of intravenous (IV) pembrolizumab (MK-3475) 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. The primary hypotheses are the following: that pembrolizumab has acceptable safety and tolerability; and that pembrolizumab shows a clinically meaningful response rate (RR) or disease-control rate (DCR) in participants with melanoma (ipilimumab-refractory or not), and a clinically meaningful RR in participants with NSCLC, especially a clinically meaningful RR in those participants with either cancer, whose tumors express PD-L1.

  • Study Type: Interventional
  • Study Design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
  • Study Primary Completion Date: January 2015

Detailed Clinical Trial Description

Part F (NSCLC) is the only part currently enrolling participants.

Interventions Used in this Clinical Trial

  • Drug: Pembrolizumab 1 mg/kg
    • IV infusion over 30 minutes on Day 1 of each cycle, at dose of 1 mg/kg
  • Drug: Pembrolizumab 3 mg/kg
    • IV infusion over 30 minutes on Day 1 of each cycle, at dose of 3 mg/kg
  • Drug: Pembrolizumab 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.
  • Drug: Pembrolizumab MEL
    • IV infusion over 30 minutes on Day 1 of each cycle
  • Drug: Pembrolizumab NSCLC
    • IV infusion over 30 minutes on Day 1 of each cycle
  • Drug: Pembrolizumab MEL Low Dose
    • IV infusion over 30 minutes every 3 weeks at dose determined during dose escalation
  • Drug: Pembrolizumab MEL High Dose
    • IV infusion over 30 minutes every 3 weeks at dose determined during dose escalation
  • Drug: Pembrolizumab NSCLC Low Dose
    • IV infusion over 30 minutes every 3 weeks at dose determined during dose escalation
  • Drug: Pembrolizumab NSCLC High Dose
    • IV infusion over 30 minutes every 2 or 3 weeks at dose determined during dose escalation
  • Drug: Pembrolizumab NSCLC Medium Dose
    • IV infusion over 30 minutes every 3 weeks at dose determined during dose escalation

Arms, Groups and Cohorts in this Clinical Trial

  • Experimental: Part A: Pembrolizumab 1 mg/kg (Closed)
    • Participants receive pembrolizumab intravenous (IV) infusion over 30 minutes on Day 1 of each cycle, at dose of 1 mg/kg
  • Experimental: Part A: Pembrolizumab 3 mg/kg (Closed)
    • Participants receive pembrolizumab intravenous (IV) infusion over 30 minutes on Day 1 of each cycle, at dose of 3 mg/kg
  • Experimental: Part A: Pembrolizumab 10 mg/kg (Closed)
    • Participants receive pembrolizumab intravenous (IV) infusion over 30 minutes on Day 1 of each cycle, at dose of 1 mg/kg
  • Experimental: Part B: Pembrolizumab MEL (Closed)
    • Participants receive pembrolizumab IV infusion over 30 minutes on Day 1 of each cycle.
  • Experimental: Part C: Pembrolizumab NSCLC (Closed)
    • Participants receive pembrolizumab IV infusion over 30 minutes on Day 1 of each cycle
  • Experimental: Part D: Pembrolizumab MEL Low Dose (Closed)
    • participants receive pembrolizumab IV infusion over 30 minutes every 3 weeks at dose determined during dose escalation
  • Experimental: Part D: Pembrolizumab MEL High Dose (Closed)
    • Participants receive pembrolizumab IV infusion over 30 minutes every 3 weeks at dose determined during dose escalation
  • Experimental: Part E: Pembrolizumab NSCLC Low Dose (Closed)
    • Participants receive pembrolizumab IV infusion over 30 minutes every 3 weeks at dose determined during dose escalation
  • Experimental: Part E: Pembrolizumab NSCLC Med. Dose (Closed)
    • Participants receive pembrolizumab IV infusion over 30 minutes every 3 weeks at dose determined during dose escalation
  • Experimental: Part E: Pembrolizumab NSCLC High Dose (Closed)
    • Participants receive pembrolizumab IV infusion over 30 minutes every 3 weeks at dose determined during dose escalation
  • Experimental: Part F: Pembrolizumab NSCLC PD-L1 Low Dose
    • Participants receive pembrolizumab IV infusion over 30 minutes every 3 weeks at dose determined during dose escalation
  • Experimental: Part F: Pembrolizumab NSCLC PD-L1 High Dose
    • Participants receive pembrolizumab IV infusion over 30 minutes every 2 or 3 weeks at dose determined during dose escalation

Outcome Measures for this Clinical Trial

Primary Measures

  • Number of participants experiencing dose-limiting toxicities (DLTs)
    • Time Frame: Cycle 1 (28 days)
      Safety Issue?: Yes
  • Number of participants experiencing clinical and laboratory adverse events (AEs)
    • Time Frame: First dose to 30 days post last dose
      Safety Issue?: Yes
  • Number of all study participants who demonstrate a response rate (RR)
    • Time Frame: Weeks 12 and 24
      Safety Issue?: No
  • Number of MEL participants who demonstrated a response rate (RR) and/or disease control rate (DCR)
    • Time Frame: Weeks 12 and 24
      Safety Issue?: No
  • Number of NSCLC participants who demonstrated a response rate (RR)
    • Time Frame: Week 9 and Week 18
      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)
      Safety Issue?: No

Secondary Measures

  • The area under the curve (AUC) of plasma concentration of drug against time after administration of pembrolizumab (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
      Safety Issue?: No
  • Maximum concentration (Cmax) after first dose interval of pembrolizumab
    • Time Frame: Part A, Cycle 1 + Day 1 of Cycle 2 and then every 14-day cycle for up to 12 months; Part B Q2W, Cycles 1 and 3; Part B Q3W, Cycles 1 and 2; Part C, Cycles 1 and 2; Part D, Cycles 1 and 6; Part E, Cycles 1 and 6; Part F, Cycles 1 and 6.
      Safety Issue?: No
  • Time at which maximum concentration (Tmax) occurs for pembrolizumab (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
      Safety Issue?: No
  • Lowest plasma concentration (C[trough]) of pembrolizumab
    • Time Frame: Part A, Cycle 1+ Day 1 Cycle 2, and each 14-day cycle for up to 12 mo.; Part B Q2W, Cycles 1,3,7 + every 4 cycles for 12 mo.; Parts B/C Q3W, Cycles 1, 2, 5 + every 4 cycles for 12 mo.; Parts D/E/F, Cycles 1, 2, 3, 6, 8 + every 4 cycles for up to 2 yrs.
      Safety Issue?: No
  • Terminal half-life (t1/2) of pembrolizumab (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 starting with Cycle 2 for up to 12 months.
      Safety Issue?: No
  • Progression free survival (PFS) in MEL and NSCLC participants
    • Time Frame: From first documented response up to 2 years
      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)
      Safety Issue?: No
  • Duration of response (DR) in MEL and NSCLC participants
    • Time Frame: From first documented response up to 2 years
      Safety Issue?: No

Criteria for Participation in this Clinical Trial

Inclusion criteria (Part F is the only part currently enrolling participants).

  • 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. In Part F, participants with Stage IV NSCLC without prior systemic therapy may be eligible.
  • 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 (Part F is the only part currently enrolling participants)

  • 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 pembrolizumab, with the exception of participants in the follow-up phase.
  • Other form(s) of antineoplastic therapy anticipated during the period of the study.
  • History of pneumonitis requiring treatment with steroids, or has a history of interstitial lung disease.
  • Medical condition that requires chronic systemic steroid therapy, or on any other form of immunosuppressive medication, excepting use of inhaled steroids.
  • History of acute diverticulitis, intra-abdominal abscess, GI obstruction, abdominal carcinomatosis.
  • History of a hematologic malignancy, malignant primary brain tumor, malignant sarcoma, or another malignant 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 pembrolizumab 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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial: No

Clinical Trial Investigator Information

  • Lead Sponsor
    • Merck Sharp & Dohme Corp.
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Medical Director, Study Director, Merck Sharp & Dohme Corp.
  • Overall Contact(s)
    • Toll Free Number, 1-888-577-8839

Source

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The URL of this page is:
http://clinicaltrialsfeeds.org/clinical-trials/show/NCT01295827