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

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ClinicalTrials.gov Identifier: NCT03302234
Recruitment Status : Recruiting
First Posted : October 5, 2017
Last Update Posted : November 16, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Carcinoma, Non-Small-Cell Lung Biological: pembrolizumab Biological: ipilimumab Other: placebo for ipilimumab Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 548 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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)
Actual Study Start Date : December 14, 2017
Estimated Primary Completion Date : February 28, 2023
Estimated Study Completion Date : February 22, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: pembrolizumab + ipilimumab
Participants 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.
Biological: pembrolizumab
Administered as an intravenous (IV) infusion every 3 weeks (Q3W)
Other Names:
  • KEYTRUDA®
  • MK-3475

Biological: ipilimumab
Administered as an IV infusion every 6 weeks (Q6W)
Other Name: YERVOY®

Active Comparator: pembrolizumab + placebo
Participants 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.
Biological: pembrolizumab
Administered as an intravenous (IV) infusion every 3 weeks (Q3W)
Other Names:
  • KEYTRUDA®
  • MK-3475

Other: placebo for ipilimumab
Normal saline solution administered as an IV infusion Q6W




Primary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: Up to approximately 2 years ]
    OS is the time from randomization to death due to any cause.

  2. Progression-free Survival (PFS) [ Time Frame: Up to approximately 2 years ]
    PFS is the time from randomization to first documented disease progression per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR).


Secondary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: Up to approximately 2 years ]
    ORR is the proportion of the participants who achieve complete response (CR) or partial response (PR) per RECIST 1.1 by BICR.

  2. Duration Of Response (DOR) [ Time Frame: Up to approximately 2 years ]
    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.

  3. 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 ]
    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.

  4. 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). ]
    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.

  5. Incidence of Discontinuations [ Time Frame: From time of signing the ICF until the end of study therapy (up to approximately 105 Weeks). ]
    Percentage of participants discontinuing study drug due to an AE.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03302234


Contacts
Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

  Show 169 Study Locations
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT03302234     History of Changes
Other Study ID Numbers: 3475-598
2016-004364-20 ( EudraCT Number )
MK-3475-598 ( Other Identifier: Merck Registration Number )
First Posted: October 5, 2017    Key Record Dates
Last Update Posted: November 16, 2018
Last Verified: November 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Merck Sharp & Dohme Corp.:
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

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Pembrolizumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs