Clinical Trials /

Study of Pembrolizumab Given With Ipilimumab or Placebo in Participants With Untreated Metastatic Non-small Cell Lung Cancer (MK-3475-598/KEYNOTE-598)

NCT03302234

Description:

The purpose of this study is to determine the efficacy of pembrolizumab given in combination with either ipilimumab or placebo as first-line treatment in participants with metastatic non-small cell lung cancer (NSCLC). The primary hypothesis of this study is that overall survival (OS) and/or progression-free survival (PFS) is prolonged in participants who receive pembrolizumab and ipilimumab compared to those who receive pembrolizumab and placebo.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Study of Pembrolizumab Given With Ipilimumab or Placebo in Participants With Untreated Metastatic Non-small Cell Lung Cancer (MK-3475-598/KEYNOTE-598)
  • Official Title: A Phase 3, Randomized, Double-Blind Study of Pembrolizumab Plus Ipilimumab vs Pembrolizumab Plus Placebo in Previously Untreated, Stage IV, Metastatic Non-small Cell Lung Cancer Subjects Whose Tumors Are PD-L1 Positive (TPS ≥ 50%) (KEYNOTE-598)

Clinical Trial IDs

  • ORG STUDY ID: 3475-598
  • SECONDARY ID: 2016-004364-20
  • SECONDARY ID: MK-3475-598
  • NCT ID: NCT03302234

Conditions

  • Carcinoma, Non-Small-Cell Lung

Interventions

DrugSynonymsArms
pembrolizumabKEYTRUDA®, MK-3475pembrolizumab + ipilimumab
ipilimumabYERVOY®pembrolizumab + ipilimumab

Purpose

The purpose of this study is to determine the efficacy of pembrolizumab given in combination with either ipilimumab or placebo as first-line treatment in participants with metastatic non-small cell lung cancer (NSCLC). The primary hypothesis of this study is that overall survival (OS) and/or progression-free survival (PFS) is prolonged in participants who receive pembrolizumab and ipilimumab compared to those who receive pembrolizumab and placebo.

Trial Arms

NameTypeDescriptionInterventions
pembrolizumab + ipilimumabExperimentalParticipants receive 200 mg of pembrolizumab by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus 1 mg/kg of ipilimumab by IV infusion on Day 1 of each 6-week cycle for up to 18 cycles of treatment.
  • pembrolizumab
  • ipilimumab
pembrolizumab + placeboActive ComparatorParticipants receive 200 mg of pembrolizumab by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus placebo by IV infusion on Day 1 of each 6-week cycle for up to 18 cycles of treatment.
  • pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Has a histologically or cytologically confirmed diagnosis of Stage IV metastatic NSCLC
             (American Joint Committee on Cancer version 8)

          -  Has measurable disease per RECIST 1.1 as determined by investigator

          -  Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  Has a life expectancy of >3 months

          -  Has provided archival tumor tissue sample or newly obtained core or excisional biopsy
             of a tumor lesion not previously irradiated

          -  Female participants of childbearing potential must have a negative serum pregnancy
             test within 72 hours prior to receiving the first dose of study therapy

          -  Female and male participants of reproductive potential must agree to use contraception
             starting from the first dose of study medication, throughout the study period, and for
             up to 120 days after the last dose of study medication

          -  Male participants must refrain from donating sperm starting from the first dose of
             study medication, throughout the study period, and for up to 120 days after the last
             dose of study medication

        Exclusion Criteria:

          -  Has received prior systemic chemotherapy/other targeted or biological antineoplastic
             therapy treatment for their Stage IV metastatic NSCLC

          -  Has a tumor that harbors an epidermal growth factor receptor (EGFR)-sensitizing
             (activating) mutation or an anaplastic lymphoma kinase (ALK) translocation

          -  Is currently participating in or has participated in a trial of an investigational
             agent or has used an investigational device within 4 weeks prior to the first dose of
             study therapy

          -  Has received prior therapy with an anti-Programmed Cell Death Receptor 1 (PD-1),
             Programmed Cell Death Receptor Ligand 1 (anti-PD-L1), or anti- Programmed Cell Death
             Receptor Ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or
             co-inhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein 4
             [CTLA-4], OX-40, CD137)

          -  Has received prior radiotherapy within 2 weeks of start of study therapy or received
             lung radiation therapy of >30 Gray (Gy) within 6 months of the first dose of study
             therapy

          -  Has recovered from all radiation-related toxicities, does not require corticosteroids,
             and has not had radiation pneumonitis

          -  Is receiving systemic steroid therapy ≤7 days prior to the first dose of study therapy
             or receiving any other form of immunosuppressive medication

          -  Has a known additional malignancy that is progressing or has required active treatment
             within the past 3 years with the exception of curatively treated basal cell carcinoma
             of the skin, squamous cell carcinoma of the skin and/or curatively resected in situ
             cancers

          -  Has known untreated central nervous system (CNS) metastases and/or carcinomatous
             meningitis

          -  Has an active autoimmune disease that has required systemic treatment in past 2 years
             (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive
             drugs)

          -  Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
             (i.e., doses exceeding 10 mg daily of prednisone equivalent) or any other form of
             immunosuppressive therapy within 7 days prior the first dose of study therapy

          -  Has a history of (non-infectious) pneumonitis that required systemic steroids or
             current pneumonitis/interstitial lung disease

          -  Has had an allogeneic tissue/solid organ transplant

          -  Has received a live vaccine within 30 days prior to the first dose of study therapy

          -  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 tuberculosis

          -  Has known psychiatric or substance abuse disorders that would interfere with
             cooperating with the requirements of the trial

          -  Is a regular user of any illicit drugs or had a recent history of substance abuse

          -  Is pregnant or breast feeding or expecting to conceive or father starting from the
             first dose of study medication, throughout the study period, and for up to 120 days
             after the last dose of study medication

          -  Has severe hypersensitivity to pembrolizumab and/or any of its excipients and/or to
             ipilimumab and/or any of its excipients

          -  Has a ROS1 translocation
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Survival (OS)
Time Frame:Up to approximately 2 years
Safety Issue:
Description:OS is the time from randomization to death due to any cause.

Secondary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:Up to approximately 2 years
Safety Issue:
Description:ORR is the proportion of the participants who achieve complete response (CR) or partial response (PR) per RECIST 1.1 by BICR.
Measure:Duration Of Response (DOR)
Time Frame:Up to approximately 2 years
Safety Issue:
Description:DOR is the time from first documented evidence of CR or PR per RECIST 1.1 by BICR until disease progression per RECIST 1.1 by BICR or death.
Measure:Time to True Deterioration (TTD) in Cough, Pain in Chest, and Shortness of Breath
Time Frame:On study day 1 prior to initiation of study therapy (baseline) and up to approximately 2 years
Safety Issue:
Description:Time to true deterioration is defined as the time to the first onset of a 10-point or greater score decrease from study day 1 prior to initiation of study therapy (baseline) in any one of the 3 symptoms, confirmed by a second adjacent 10-point or greater score decrease from baseline. Cough is based on European Organization for Research and Treatment of Cancer Quality of Life Questionnaire and Lung Cancer Module 13 (EORTC QLQ-LC13) question 1, pain in chest is based on EORTC QLQ-LC13 question 10, and shortness of breath is based on European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) question 8.
Measure:Incidence of Adverse Events (AEs)
Time Frame:From time of signing the informed consent form (ICF) until the end of follow-up (up to approximately 118 Weeks).
Safety Issue:
Description:Percentage of participants experiencing any unfavorable and unintended sign, symptom, disease, or worsening of pre-existing condition temporally associated with study therapy and irrespective of causality to study therapy.
Measure:Incidence of Discontinuations
Time Frame:From time of signing the ICF until the end of study therapy (up to approximately 105 Weeks).
Safety Issue:
Description:Percentage of participants discontinuing study drug due to an AE.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Merck Sharp & Dohme Corp.

Trial Keywords

  • Programmed Cell Death Receptor 1 (PD-1)
  • Programmed Cell Death Receptor Ligand 1 (PD-L1)
  • Cytotoxic T-lymphocyte-associated protein 4 (CTLA4)
  • PD1
  • PD-1
  • PDL1
  • PD-L1
  • CTLA4

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