Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03302234
Recruitment Status : Active, not recruiting
First Posted : October 5, 2017
Last Update Posted : December 29, 2020
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE September 26, 2017
First Posted Date  ICMJE October 5, 2017
Last Update Posted Date December 29, 2020
Actual Study Start Date  ICMJE December 14, 2017
Actual Primary Completion Date September 1, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 22, 2020)
  • Overall Survival (OS) [ Time Frame: Up to approximately 27 months ]
    OS is the time from randomization to death due to any cause.
  • Progression-free Survival (PFS) [ Time Frame: Up to approximately 19 months ]
    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).
Original Primary Outcome Measures  ICMJE
 (submitted: October 4, 2017)
  • Overall Survival (OS) [ Time Frame: Up to approximately 2 years ]
    OS is the time from randomization to death due to any cause.
  • 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).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 22, 2020)
  • Objective Response Rate (ORR) [ Time Frame: Up to approximately 27 months ]
    ORR is the proportion of the participants who achieve complete response (CR) or partial response (PR) per RECIST 1.1 by BICR.
  • Duration Of Response (DOR) [ Time Frame: Up to approximately 27 months ]
    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.
  • Time to True Deterioration (TTD) in Cough, Pain in Chest, and Shortness of Breath [ Time Frame: Up to approximately 27 months ]
    Time to true deterioration is defined as the time to the first onset of a 10-point or greater score deterioration 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 deterioration 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.
  • Incidence of Adverse Events (AEs) [ Time Frame: Up to approximately 30 months ]
    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.
  • Incidence of Discontinuations [ Time Frame: Up to approximately 27 months ]
    Percentage of participants discontinuing study drug due to an AE.
  • Change from Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status/Quality of Life (Items 29 and 30) Scale Score [ Time Frame: Baseline and up to approximately 27 months ]
    The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?" are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status. The change from baseline in EORTC QLQ-C30 Items 29 and 30 scale scores will be presented.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 4, 2017)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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)
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.

With Amendment 6 (effective date: 11-Dec-2020), active participants, investigator, and sponsor personnel or delegate(s) involved in the treatment administration or clinical evaluation of the participants will be unblinded. Participants will discontinue ipilimumab and placebo to ipilimumab and participants who remain on treatment will receive open-label pembrolizumab only.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Carcinoma, Non-Small-Cell Lung
Intervention  ICMJE
  • 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®
  • Other: placebo for ipilimumab
    Normal saline solution administered as an IV infusion Q6W
Study Arms  ICMJE
  • 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.
    Interventions:
    • Biological: pembrolizumab
    • Biological: ipilimumab
  • 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.
    Interventions:
    • Biological: pembrolizumab
    • Other: placebo for ipilimumab
Publications * Boyer M, Şendur MAN, Rodríguez-Abreu D, Park K, Lee DH, Çiçin I, Yumuk PF, Orlandi FJ, Leal TA, Molinier O, Soparattanapaisarn N, Langleben A, Califano R, Medgyasszay B, Hsia TC, Otterson GA, Xu L, Piperdi B, Samkari A, Reck M; KEYNOTE-598 Investigators. Pembrolizumab Plus Ipilimumab or Placebo for Metastatic Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score ≥ 50%: Randomized, Double-Blind Phase III KEYNOTE-598 Study. J Clin Oncol. 2021 Jan 29:JCO2003579. doi: 10.1200/JCO.20.03579. [Epub ahead of print]

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: July 22, 2020)
568
Original Estimated Enrollment  ICMJE
 (submitted: October 4, 2017)
548
Estimated Study Completion Date  ICMJE February 22, 2024
Actual Primary Completion Date September 1, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 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

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 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Brazil,   Canada,   Chile,   Colombia,   France,   Germany,   Hungary,   Ireland,   Italy,   Korea, Republic of,   Latvia,   Mexico,   Peru,   Poland,   South Africa,   Spain,   Taiwan,   Thailand,   Turkey,   Ukraine,   United Kingdom,   United States
Removed Location Countries Russian Federation
 
Administrative Information
NCT Number  ICMJE NCT03302234
Other Study ID Numbers  ICMJE 3475-598
2016-004364-20 ( EudraCT Number )
MK-3475-598 ( Other Identifier: Merck )
KEYNOTE-598 ( Other Identifier: Merck )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pd
URL: http://engagezone.msd.com/ds_documentation.php
Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme Corp.
PRS Account Merck Sharp & Dohme Corp.
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP