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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03066778




Registration number
NCT03066778
Ethics application status
Date submitted
23/02/2017
Date registered
28/02/2017
Date last updated
3/10/2022

Titles & IDs
Public title
A Study of Pembrolizumab (MK-3475) in Combination With Etoposide/Platinum (Cisplatin or Carboplatin) for Participants With Extensive Stage Small Cell Lung Cancer (MK-3475-604/KEYNOTE-604)
Scientific title
A Phase 3 Randomized, Double-Blind, Placebo-controlled Trial of Pembrolizumab (MK-3475/SCH900475) in Combination With Etoposide/Platinum (Cisplatin or Carboplatin) for the First-line Treatment of Subjects With Extensive Stage Small Cell Lung Cancer (KEYNOTE-604)
Secondary ID [1] 0 0
173744
Secondary ID [2] 0 0
3475-604
Universal Trial Number (UTN)
Trial acronym
Linked study record

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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Pembrolizumab
Treatment: Drugs - Normal saline solution
Treatment: Drugs - Carboplatin
Treatment: Drugs - Cisplatin
Treatment: Drugs - Etoposide

Experimental: Pembrolizumab+EP - During each 21-day cycle, participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 PLUS etoposide 100 mg/m^2 IV on Days 1, 2 and 3 PLUS investigator's choice of platinum therapy (carboplatin titrated to an area under the plasma drug concentration-time curve [AUC] 5 IV on Day 1 OR cisplatin 75 mg/m^2 IV on Day 1). Participants who stop pembrolizumab as a result of obtaining a response of stable disease (SD), partial response (PR), complete response (CR) or those who stop after receiving pembrolizumab for 24 months for reasons other than disease progression or intolerability, are eligible for up to an additional 1 year of treatment after progressive disease if they meet the criteria for retreatment.

Active Comparator: Placebo+EP - During each 21-day cycle, participants receive placebo (normal saline solution) IV on Day 1 PLUS etoposide 100 mg/m^2 IV on Days 1, 2 and 3 PLUS investigator's choice of platinum therapy (carboplatin titrated to an AUC 5 IV on Day 1 OR cisplatin 75 mg/m^2 IV on Day 1).


Other interventions: Pembrolizumab
IV infusion on Day 1 of each cycle prior to chemotherapy

Treatment: Drugs: Normal saline solution
IV infusion on Day 1 of each cycle prior to chemotherapy

Treatment: Drugs: Carboplatin
IV infusion on Day 1 of each cycle

Treatment: Drugs: Cisplatin
IV infusion on Day 1 of each cycle

Treatment: Drugs: Etoposide
IV infusion on Days 1, 2 and 3 of each cycle
Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
Timepoint [1] 0 0
Up to approximately 30.5 months
Primary outcome [2] 0 0
Overall Survival (OS)
Timepoint [2] 0 0
Up to approximately 30.5 months
Secondary outcome [1] 0 0
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
Timepoint [1] 0 0
Up to approximately 30.5 months
Secondary outcome [2] 0 0
Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
Timepoint [2] 0 0
Up to approximately 30.5 months
Secondary outcome [3] 0 0
Number of Participants Who Experienced an Adverse Event (AE)
Timepoint [3] 0 0
Up to approximately 30.5 months
Secondary outcome [4] 0 0
Number of Participants Discontinuing Study Treatment Due to an Adverse Event (AE)
Timepoint [4] 0 0
Up to approximately 26 months
Secondary outcome [5] 0 0
Number of Participants Experiencing Any Grade 3 to 5 Adverse Events (AE) as Assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE 4.03)
Timepoint [5] 0 0
Up to approximately 30.5 months
Secondary outcome [6] 0 0
Change From Baseline at Week 18 in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Global Health Status/Quality of Life Scale
Timepoint [6] 0 0
Baseline (prior to first dose of study treatment in Cycle 1 [cycle length = 21 days]) and Week 18
Secondary outcome [7] 0 0
Change From Baseline at Week 12 in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Global Health Status/Quality of Life Scale
Timepoint [7] 0 0
Baseline (prior to first dose of study treatment in Cycle 1 [cycle length = 21 days]) and Week 12
Secondary outcome [8] 0 0
Change From Baseline at Week 24 in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Global Health Status/Quality of Life Scale
Timepoint [8] 0 0
Baseline (prior to first dose of study treatment in Cycle 1 [cycle length = 21 days]) and Week 24
Secondary outcome [9] 0 0
Time to True Deterioration (TTD) in the Composite Endpoint of Cough, Chest Pain, and Dyspnea Using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) and Lung Cancer Module 13 (QLQ-LC13)
Timepoint [9] 0 0
Day 1 of Cycles 1-9, Day 1 of every other cycle for Cycles 10-17 and 30 days after last dose of study treatment (Up to approximately 27 months)

Eligibility
Key inclusion criteria
- Has a documented new diagnosis of SCLC by histology or cytology from brushing,
washing, or needle aspiration of a defined lesion. Participants who do not have
histology samples (defined as core or excisional biopsy, or resections) will need to
undergo a new biopsy to provide a tissue sample.

- Has extensive-stage disease defined as Stage IV (T any, N any, M 1a/b) by the American
Joint Committee on Cancer (AJCC), Seventh Edition

- Has =1 lesion that meets the criteria for measurable, as defined by RECIST 1.1, and is
appropriate for selection as a target lesion, as determined by local site
investigator/radiology assessment

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

- Has Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

- Has a life expectancy of =3 months

- Has adequate organ function

- Female and male participants of childbearing potential must be willing to use an
adequate method of contraception, starting with the first dose of study treatment
through 120 days after the last dose of study treatment and up to 180 days after last
dose of chemotherapeutic agents
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Has received prior systemic therapy for the treatment of SCLC

- Is currently participating and receiving study treatment or has participated in a
study of an investigational agent and received study treatment or used an
investigational device within 4 weeks of the first dose of treatment for another
health-related problem

- Is expected to require any other form of antineoplastic therapy for SCLC, including
radiation therapy, while on study. (Prophylactic cranial irradiation will be possible
for those participants with stable disease or better at the completion of the 4 cycles
of chemotherapy with or without pembrolizumab.)

- Has known central nervous system (ie, brain and/or spinal cord) metastases and/or
carcinomatous meningitis. Participants with brain metastases may participate only if
they satisfy all of the following:

- Has completed treatment (eg, whole brain radiation treatment [WBRT], stereotactic
radiosurgery, or equivalent) =14 days prior to the first dose of study treatment,

- Has no evidence of new or enlarging brain metastases confirmed by post-treatment
repeat brain imaging performed =3 weeks after pre-treatment brain imaging, and

- Is neurologically stable without the need for steroids for =7 days before first dose
of study treatment.

- Has had major surgery within 3 weeks prior to receiving the first dose of study
treatment or has not recovered adequately from toxicity and/or complications from an
intervention prior to receiving the first dose of study treatment.

- Has a history of (non-infectious) pneumonitis that required steroids or has current
pneumonitis

- Has a known history of interstitial lung disease

- Has a known additional malignancy that is progressing or requires active treatment.
Exceptions include early stage cancers (carcinoma in situ or Stage 1) treated with
curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the
skin, in situ cervical cancer, or in situ breast cancer that has undergone potentially
curative therapy.

- Has active autoimmune disease that has required systemic treatment in the past 2
years. Replacement therapy is not considered a form of systemic treatment.

- Has a known history of, or active, neurologic paraneoplastic syndrome

- Has clinically active diverticulitis, intra-abdominal abscess, gastrointestinal
obstruction, and/or abdominal carcinomatosis

- Has a history of a severe hypersensitivity reaction to treatment with another
monoclonal antibody

- Is taking chronic systemic steroids (in doses exceeding 10 mg daily of prednisone
equivalent) within 7 days prior to the first dose of study treatment

- Has a diagnosis of immunodeficiency or is receiving any form of immunosuppressive
therapy within 7 days prior to the first dose of study treatment

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

- Has received prior therapy with an anti-programmed cell death protein-1 (anti-PD-1),
anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-programmed cell death-ligand
2 (anti-PD-L2) agent or with an agent directed to another co-inhibitory T-cell
receptor (i.e., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], tumor necrosis
factor receptor superfamily member 9 [TNFRSF9, OX-40, CD137]) or has previously
participated in a Merck pembrolizumab (MK-3475) clinical trial

- Has severe hypersensitivity (Grade =3) to pembrolizumab and/or any of its excipients

- 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 TB (Bacillus Tuberculosis)

- Has symptomatic ascites or pleural effusion. A participant who is clinically stable
following treatment for these conditions (including therapeutic thoraco- or
paracentesis) is eligible.

- Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the study starting with the screening visit through 120 days
after the last dose of study treatment through and up to 180 days after last dose of
chemotherapeutic agents

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
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
2/05/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
21/09/2021
Sample size
Target
Accrual to date
Final
453
Recruitment in Australia
Recruitment state(s)
NSW,WA
Recruitment hospital [1] 0 0
Blacktown Hospital ( Site 0004) - Blacktown
Recruitment hospital [2] 0 0
Southern Medical Day Care Centre ( Site 0001) - Wollongong
Recruitment hospital [3] 0 0
St John of God ( Site 0006) - Murdoch
Recruitment hospital [4] 0 0
Lyell McEwin Hospital ( Site 0002) - Elizabeth Vale
Recruitment hospital [5] 0 0
St Vincents Hospital Melbourne ( Site 0005) - Fitzroy
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
2500 - Wollongong
Recruitment postcode(s) [3] 0 0
6150 - Murdoch
Recruitment postcode(s) [4] 0 0
5112 - Elizabeth Vale
Recruitment postcode(s) [5] 0 0
3065 - Fitzroy
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Illinois
Country [3] 0 0
United States of America
State/province [3] 0 0
Indiana
Country [4] 0 0
United States of America
State/province [4] 0 0
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
Minnesota
Country [8] 0 0
United States of America
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Mississippi
Country [9] 0 0
United States of America
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Missouri
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United States of America
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Nevada
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United States of America
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New Jersey
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United States of America
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New York
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United States of America
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North Carolina
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United States of America
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South Carolina
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United States of America
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Tennessee
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United States of America
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Texas
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Canada
State/province [17] 0 0
Manitoba
Country [18] 0 0
Canada
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Nova Scotia
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Canada
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Ontario
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Canada
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Quebec
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Chile
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Region Metropolitana
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Chile
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Santiago
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Chile
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Talca
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France
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Lille
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France
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Limoges
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France
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Nantes
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France
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Nice
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France
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Paris
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France
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Reims
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France
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Toulouse
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Germany
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Berlin
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Germany
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Dresden
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Germany
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Duesseldorf
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Germany
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Gera
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Germany
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Hamburg
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Germany
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Heidelberg
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Marburg
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Tuebingen
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Pest
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Budapest
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Hungary
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Farkasgyepu
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Gyor
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Hungary
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Szekesfehervar
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Szolnok
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Hungary
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Zalaegerszeg
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Ireland
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Dublin
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Israel
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Beer Sheva
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Israel
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Haifa
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Israel
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Kfar Saba
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Israel
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Petah Tikva
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Israel
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Ramat-Gan
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Japan
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Aichi
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Japan
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Chiba
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Ehime
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Japan
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Fukuoka
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Japan
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Hyogo
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Japan
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Kanagawa
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Japan
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Miyagi
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Japan
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Osaka
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Japan
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Shizuoka
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Japan
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Yamaguchi
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Japan
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Hiroshima
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Japan
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Niigata
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Japan
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Tokyo
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Japan
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Wakayama
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Korea, Republic of
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Busan
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Korea, Republic of
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Goyang-si
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Korea, Republic of
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Seoul
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New Zealand
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Christchurch
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Poland
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Mazowieckie
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Poland
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Konin
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Poland
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Krakow
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Poland
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Lublin
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Poland
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Poznan
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Poland
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Torun
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Poland
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Warszawa
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Poland
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Wroclaw
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Russian Federation
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Belgorod
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Russian Federation
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Moscow
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Russian Federation
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Pyatigorsk
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Russian Federation
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Saint Petersburg
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Spain
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Gran Canaria
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Spain
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A Coruna
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Spain
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Barcelona
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Spain
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Jaen
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Spain
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Madrid
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Spain
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Valencia
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Switzerland
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Chur
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Switzerland
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Lausanne
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Switzerland
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Zuerich
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Taiwan
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Kaohsiung
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Taiwan
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Taichung
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Taiwan
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Tainan
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Taiwan
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Taipei
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Turkey
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Bornova
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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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Edirne
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Turkey
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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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United Kingdom
State/province [103] 0 0
Birmingham
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United Kingdom
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Leeds
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United Kingdom
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London
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United Kingdom
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Maidstone
Country [107] 0 0
United Kingdom
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Northwood

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

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to assess the safety and efficacy of pembrolizumab plus standard
of care (SOC) chemotherapy (etoposide/platinum [EP]) in participants with newly diagnosed
extensive stage small cell lung cancer (ES-SCLC) who have not previously received systemic
therapy for this malignancy.

The primary study hypotheses are that pembrolizumab+EP prolongs Progression-free Survival
(PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by blinded
independent central review (BICR) and Overall Survival (OS) compared with placebo+EP in adult
participants with ES-SCLC. In this study, RECIST 1.1 has been modified to follow a maximum of
10 target lesions and a maximum of 5 target lesions per organ.

With protocol Amendment 07 (03-Oct-2018), the outcome measure of "Change from Baseline at
Weeks 12 and 24 in European Organization for Research and Treatment of Cancer (EORTC) Quality
of Life Questionnaire Core 30 (QLQ-C30) Global Health Status/Quality of Life Scale" was
replaced with a single time point analysis at Week 18.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03066778
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
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

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03066778