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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03302234




Registration number
NCT03302234
Ethics application status
Date submitted
26/09/2017
Date registered
5/10/2017
Date last updated
2/08/2019

Titles & IDs
Public title
Study of Pembrolizumab Given With Ipilimumab or Placebo in Participants With Untreated Metastatic Non-small Cell Lung Cancer (MK-3475-598/KEYNOTE-598)
Scientific 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)
Secondary ID [1] 0 0
2016-004364-20
Secondary ID [2] 0 0
3475-598
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Carcinoma, Non-Small-Cell Lung 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Non small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - pembrolizumab
Other interventions - ipilimumab
Other interventions - placebo for ipilimumab

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.

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.


Other interventions: pembrolizumab
Administered as an intravenous (IV) infusion every 3 weeks (Q3W)

Other interventions: ipilimumab
Administered as an IV infusion every 6 weeks (Q6W)

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

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS) - OS is the time from randomization to death due to any cause.
Timepoint [1] 0 0
Up to approximately 2 years
Primary outcome [2] 0 0
Progression-free Survival (PFS) - 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).
Timepoint [2] 0 0
Up to approximately 2 years
Secondary outcome [1] 0 0
Objective Response Rate (ORR) - ORR is the proportion of the participants who achieve complete response (CR) or partial response (PR) per RECIST 1.1 by BICR.
Timepoint [1] 0 0
Up to approximately 2 years
Secondary outcome [2] 0 0
Duration Of Response (DOR) - 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.
Timepoint [2] 0 0
Up to approximately 2 years
Secondary outcome [3] 0 0
Time to True Deterioration (TTD) in Cough, Pain in Chest, and Shortness of Breath - 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.
Timepoint [3] 0 0
On study day 1 prior to initiation of study therapy (baseline) and up to approximately 2 years
Secondary outcome [4] 0 0
Incidence of Adverse Events (AEs) - 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.
Timepoint [4] 0 0
From time of signing the informed consent form (ICF) until the end of follow-up (up to approximately 118 Weeks).
Secondary outcome [5] 0 0
Incidence of Discontinuations - Percentage of participants discontinuing study drug due to an AE.
Timepoint [5] 0 0
From time of signing the ICF until the end of study therapy (up to approximately 105 Weeks).

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,WA
Recruitment hospital [1] 0 0
Mater Cancer Care Centre ( Site 2102) - South Brisbane
Recruitment hospital [2] 0 0
Fiona Stanley Hospital ( Site 2105) - Perth
Recruitment hospital [3] 0 0
Chris OBrien Lifehouse ( Site 2100) - Camperdown
Recruitment hospital [4] 0 0
The Townsville Hospital ( Site 2103) - Douglas
Recruitment hospital [5] 0 0
St Vincents Hospital Melbourne ( Site 2101) - Fitzroy
Recruitment postcode(s) [1] 0 0
4101 - South Brisbane
Recruitment postcode(s) [2] 0 0
6150 - Perth
Recruitment postcode(s) [3] 0 0
2050 - Camperdown
Recruitment postcode(s) [4] 0 0
4814 - Douglas
Recruitment postcode(s) [5] 0 0
3065 - Fitzroy
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
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United States of America
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California
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Florida
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Kentucky
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Maine
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Massachusetts
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New York
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Oregon
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South Carolina
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Tennessee
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Texas
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Washington
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Wisconsin
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Argentina
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Rio Negro
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Argentina
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Santa Fe
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Argentina
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Buenos Aires
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Cordoba
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Argentina
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La Rioja
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Rosario
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Argentina
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Tucuman
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Brazil
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Pernambuco
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Brazil
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Rio Grande Do Sul
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Brazil
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RS
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Brazil
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SP
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Brazil
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Barretos
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Brazil
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Florianopolis
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Brazil
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Sao Paulo
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Canada
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Alberta
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Canada
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Manitoba
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Canada
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Quebec
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Chile
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El Maule
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Chile
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Santiago
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Chile
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Vina del Mar
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Colombia
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Bogota
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Pasto
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Gera
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Brzeziny
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Konin
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Olsztyn
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Poznan
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South Africa
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Free State
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South Africa
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Gauteng
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South Africa
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Cape Town
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South Africa
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Durban
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South Africa
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Johannesburg
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South Africa
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Kraaifontein
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Barcelona
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Spain
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Changhua
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Taiwan
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Tainan
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Taiwan
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Taipei
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Taiwan
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Taoyuan
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Thailand
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Bangkok
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Thailand
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Chiang Mai
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Thailand
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Khon Kaen
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Turkey
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Adana
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Turkey
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Ankara
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Turkey
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Bursa
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Turkey
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Cankaya - Ankara
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Turkey
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Edirne
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Istanbul
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Turkey
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Izmir
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Turkey
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Kocaeli
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Turkey
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Malatya
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Turkey
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Trabzon
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Ukraine
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Dnipropetrovsk Region
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Ukraine
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Cherkasy
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Ukraine
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Chernivtsy
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Ukraine
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Dnipropetrovsk
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Ukraine
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Ivano-Frankivsk
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Ukraine
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Kropyvnytskyi
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Ukraine
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Kyiv
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Ukraine
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Lviv
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Ukraine
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Odesa
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United Kingdom
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Cornwall
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United Kingdom
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Surrey
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United Kingdom
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Belfast
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United Kingdom
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London
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United Kingdom
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Manchester
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United Kingdom
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Northwood
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United Kingdom
State/province [135] 0 0
Wolverhampton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Merck Sharp & Dohme Corp.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03302234
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme Corp.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications