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    Clinical Trial Results:
    A Phase 3 Randomized, Double-Blind Clinical Study of Pembrolizumab + Epacadostat vs Pembrolizumab + Placebo as a Treatment for Recurrent or Progressive Metastatic Urothelial Carcinoma in Patients who have Failed a First-Line Platinum-containing Chemotherapy Regimen for Advanced/Metastatic Disease (KEYNOTE- 698/ECHO-303)

    Summary
    EudraCT number
    		 2017-002310-31
    Trial protocol
    		 DE   DK   GB   NL   ES   HU   FR   IT  
    Global end of trial date
    27 Jul 2020

    Results information
    Results version number
    		 v1(current)
    This version publication date
    18 Nov 2021
    First version publication date
    18 Nov 2021
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    KEYNOTE-698/ECHO-303
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Incyte
    Sponsor organisation address
    1801 Augustine Cutoff drive, Wilmington, United States, 19803
    Public contact
    Study Director, Incyte Corporation, +1 8554633463, medinfo@incyte.com
    Scientific contact
    Study Director, Incyte Corporation, +1 8554633463, medinfo@incyte.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    27 Jul 2020
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    27 Jul 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The purpose of this study was to evaluate the efficacy and safety of pembrolizumab + epacadostat vs pembrolizumab + placebo as a treatment for recurrent or progressive metastatic urothelial carcinoma in patients who have failed a first-line platinum-containing chemotherapy regimen for advanced/metastatic disease.
    Protection of trial subjects
    Participants should receive appropriate supportive care measures as deemed necessary by the treating investigator, including, but not limited to,the items outlined below. -Nausea/vomiting: Nausea and vomiting should be treated aggressively, and consideration should be given in subsequent cycles to the administration of prophylactic antiemetic therapy according to standard institutional practice. Subjects should be strongly encouraged to maintain liberal oral fluid intake. -Anti-infectives: Subjects with a documented infectious complication should receive oral or IV antibiotics or other anti-infective agents as considered appropriate by the treating investigator for a given infectious condition, according to standard institutional practice.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    22 Dec 2017
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 9
    Country: Number of subjects enrolled
    Canada: 2
    Country: Number of subjects enrolled
    Denmark: 6
    Country: Number of subjects enrolled
    Spain: 11
    Country: Number of subjects enrolled
    France: 6
    Country: Number of subjects enrolled
    Ireland: 1
    Country: Number of subjects enrolled
    Israel: 9
    Country: Number of subjects enrolled
    Italy: 1
    Country: Number of subjects enrolled
    Japan: 2
    Country: Number of subjects enrolled
    Korea, Republic of: 5
    Country: Number of subjects enrolled
    Russian Federation: 9
    Country: Number of subjects enrolled
    Turkey: 17
    Country: Number of subjects enrolled
    Taiwan: 4
    Country: Number of subjects enrolled
    United States: 2
    Worldwide total number of subjects
    84
    EEA total number of subjects
    25
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    33
    From 65 to 84 years
    50
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    		 This study was conducted at 82 centers in 16 countries.

    Pre-assignment
    Screening details
    		 Participants were stratified by the Bellmunt score (0 vs 1 vs ≥2) and by programmed deathligand 1 expression (combined positive score [CPS] ≥10 vs CPS <10), as assessed by central laboratory, and then randomized 1:1 to either pembrolizumab + epacadostat or pembrolizumab + placebo.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Pembrolizumab 200 mg Q3W + Epacadostat 100 mg BID
    Arm description
    		 Pembrolizumab administered intravenously Day 1 of each cycle every 3 weeks. Epacadostat administered orally twice daily.
    Arm type
    		 Experimental

    Investigational medicinal product name
    epacadostat
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    100 mg

    Investigational medicinal product name
    pembrolizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    200 mg

    Arm title
    		 Pembrolizumab 200 mg Q3W + placebo BID
    Arm description
    		 Pembrolizumab administered intravenously Day 1 of each cycle every 3 weeks. Matching placebo administered orally twice daily.
    Arm type
    		 Placebo

    Investigational medicinal product name
    pembrolizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intracavernous use
    Dosage and administration details
    200 mg

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    palcebo

    Number of subjects in period 1
    		Pembrolizumab 200 mg Q3W + Epacadostat 100 mg BID Pembrolizumab 200 mg Q3W + placebo BID
    Started
    42
    42
    Intention-to-Treat (ITT)
    42
    42
    All Participants as Treated (APaT)
    42
    41
    Completed
    23
    28
    Not completed
    19
    14
         Adverse event, serious fatal
    13
    13
         Consent withdrawn by subject
    3
    1
         Physician decision
    3
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Pembrolizumab 200 mg Q3W + Epacadostat 100 mg BID
    Reporting group description
    		 Pembrolizumab administered intravenously Day 1 of each cycle every 3 weeks. Epacadostat administered orally twice daily.

    Reporting group title
    Pembrolizumab 200 mg Q3W + placebo BID
    Reporting group description
    		 Pembrolizumab administered intravenously Day 1 of each cycle every 3 weeks. Matching placebo administered orally twice daily.

    Reporting group values
    		 Pembrolizumab 200 mg Q3W + Epacadostat 100 mg BID Pembrolizumab 200 mg Q3W + placebo BID Total
    Number of subjects
    		 42 42 84
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 15 18 33
        From 65-84 years
    		 26 24 50
        85 years and over
    		 1 0 1
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 67.9 ± 8.7 65.2 ± 10.0 -
    Sex: Female, Male
    Units:
        Female
    		 7 5 12
        Male
    		 35 37 72
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 0 0 0
        Not Hispanic or Latino
    		 38 37 75
        Unknown or Not Reported
    		 4 4 8
        Missing
    		 0 1 1
    Race/Ethnicity, Customized
    Units: Subjects
        Asian
    		 5 6 11
        White
    		 35 32 67
        Missing
    		 2 4 6
    Metastasis Status at Screening
    Units: Subjects
        Metastatic
    		 35 40 75
        Advanced/Unresectable
    		 7 2 9

    End points

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    End points reporting groups
    Reporting group title
    Pembrolizumab 200 mg Q3W + Epacadostat 100 mg BID
    Reporting group description
    		 Pembrolizumab administered intravenously Day 1 of each cycle every 3 weeks. Epacadostat administered orally twice daily.

    Reporting group title
    Pembrolizumab 200 mg Q3W + placebo BID
    Reporting group description
    		 Pembrolizumab administered intravenously Day 1 of each cycle every 3 weeks. Matching placebo administered orally twice daily.

    Primary: Objective response rate (ORR) with pembrolizumab + epacadostat versus pembrolizumab + placebo

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    End point title
    		 Objective response rate (ORR) with pembrolizumab + epacadostat versus pembrolizumab + placebo [1]
    End point description
    ORR was defined as the percentage of participants who had a complete response (CR), disappearance of all target lesions or partial response (PR), >=30% decrease in the sum of the longest diameter of target lesions per RECIST v1.1 by investigator determination.
    End point type
    Primary
    End point timeframe
    up to 9 weeks +14 days
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analyses for this end point
    End point values
    		 Pembrolizumab 200 mg Q3W + Epacadostat 100 mg BID Pembrolizumab 200 mg Q3W + placebo BID
    Number of subjects analysed
    42
    42
    Units: percentage of participants
        number (confidence interval 95%)
    21.4 (12.49 to 43.26)
    9.5 (3.11 to 26.06)
    No statistical analyses for this end point

    Secondary: Safety and Tolerability of pembrolizumab + epacadostat versus pembrolizumab + placebo as measured by Number of Participants Experiencing Adverse Events (AEs)

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    End point title
    		 Safety and Tolerability of pembrolizumab + epacadostat versus pembrolizumab + placebo as measured by Number of Participants Experiencing Adverse Events (AEs)
    End point description
    AE is defined as any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.
    End point type
    Secondary
    End point timeframe
    Up to 8 months
    End point values
    		 Pembrolizumab 200 mg Q3W + Epacadostat 100 mg BID Pembrolizumab 200 mg Q3W + placebo BID
    Number of subjects analysed
    42
    41
    Units: Participants
    42
    39
    No statistical analyses for this end point

    Secondary: Safety and Tolerability of pembrolizumab + epacadostat versus pembrolizumab + placebo as Measured by Number of Participants Discontinuing Study Treatment Due to AE

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    End point title
    		 Safety and Tolerability of pembrolizumab + epacadostat versus pembrolizumab + placebo as Measured by Number of Participants Discontinuing Study Treatment Due to AE
    End point description
    AE is defined as any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.
    End point type
    Secondary
    End point timeframe
    Up to 8 months
    End point values
    		 Pembrolizumab 200 mg Q3W + Epacadostat 100 mg BID Pembrolizumab 200 mg Q3W + placebo BID
    Number of subjects analysed
    42
    41
    Units: Participants
    4
    6
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to 8 Months
    Adverse event reporting additional description
    AE additional description
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22
    Reporting groups
    Reporting group title
    Pembrolizumab 200 mg Q3W + Epacadostat 100 mg BID
    Reporting group description
    		 Pembrolizumab administered intravenously Day 1 of each cycle every 3 weeks. Epacadostat administered orally twice daily.

    Reporting group title
    Total
    Reporting group description
    		 Total

    Reporting group title
    Pembrolizumab Q3W 200 mg + Placebo BID
    Reporting group description
    		 Pembrolizumab administered intravenously Day 1 of each cycle every 3 weeks. Matching placebo administered orally twice daily.

    Serious adverse events
    		 Pembrolizumab 200 mg Q3W + Epacadostat 100 mg BID Total Pembrolizumab Q3W 200 mg + Placebo BID
    Total subjects affected by serious adverse events
         subjects affected / exposed
    22 / 42 (52.38%)
    38 / 83 (45.78%)
    16 / 41 (39.02%)
         number of deaths (all causes)
    14
    32
    18
         number of deaths resulting from adverse events
    7
    14
    7
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    1 / 42 (2.38%)
    1 / 83 (1.20%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Malignant neoplasm progression
         subjects affected / exposed
    9 / 42 (21.43%)
    15 / 83 (18.07%)
    6 / 41 (14.63%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 16
    0 / 6
         deaths causally related to treatment / all
    0 / 6
    0 / 12
    0 / 6
    Squamous cell carcinoma
         subjects affected / exposed
    1 / 42 (2.38%)
    1 / 83 (1.20%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Disease progression
         subjects affected / exposed
    1 / 42 (2.38%)
    1 / 83 (1.20%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Haemophagocytic lymphohistiocytosis
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 83 (1.20%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Pelvic pain
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 83 (1.20%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Bronchitis chronic
         subjects affected / exposed
    1 / 42 (2.38%)
    1 / 83 (1.20%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 42 (2.38%)
    1 / 83 (1.20%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Organising pneumonia
         subjects affected / exposed
    1 / 42 (2.38%)
    1 / 83 (1.20%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    1 / 42 (2.38%)
    1 / 83 (1.20%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    1 / 42 (2.38%)
    1 / 83 (1.20%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    1 / 42 (2.38%)
    1 / 83 (1.20%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    Investigations
    Amylase increased
         subjects affected / exposed
    1 / 42 (2.38%)
    1 / 83 (1.20%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Radius fracture
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 83 (1.20%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract stoma complication
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 83 (1.20%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    1 / 42 (2.38%)
    1 / 83 (1.20%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    1 / 42 (2.38%)
    2 / 83 (2.41%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Nervous system disorders
    Ataxia
         subjects affected / exposed
    1 / 42 (2.38%)
    1 / 83 (1.20%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypoxic-ischaemic encephalopathy
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 83 (1.20%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral motor neuropathy
         subjects affected / exposed
    1 / 42 (2.38%)
    1 / 83 (1.20%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 42 (2.38%)
    2 / 83 (2.41%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Diverticular perforation
         subjects affected / exposed
    1 / 42 (2.38%)
    1 / 83 (1.20%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorder
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 83 (1.20%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    2 / 42 (4.76%)
    2 / 83 (2.41%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 42 (2.38%)
    1 / 83 (1.20%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis acute
         subjects affected / exposed
    1 / 42 (2.38%)
    1 / 83 (1.20%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 83 (1.20%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chronic kidney disease
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 83 (1.20%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    2 / 42 (4.76%)
    3 / 83 (3.61%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    1 / 42 (2.38%)
    1 / 83 (1.20%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 83 (1.20%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Bacteraemia
         subjects affected / exposed
    1 / 42 (2.38%)
    1 / 83 (1.20%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 83 (1.20%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 83 (1.20%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    1 / 42 (2.38%)
    1 / 83 (1.20%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 42 (2.38%)
    1 / 83 (1.20%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    3 / 42 (7.14%)
    6 / 83 (7.23%)
    3 / 41 (7.32%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 10
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hyperkalaemia
         subjects affected / exposed
    1 / 42 (2.38%)
    1 / 83 (1.20%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Pembrolizumab 200 mg Q3W + Epacadostat 100 mg BID Total Pembrolizumab Q3W 200 mg + Placebo BID
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    39 / 42 (92.86%)
    74 / 83 (89.16%)
    35 / 41 (85.37%)
    Investigations
    Amylase increased
         subjects affected / exposed
    4 / 42 (9.52%)
    6 / 83 (7.23%)
    2 / 41 (4.88%)
         occurrences all number
    4
    8
    4
    Blood alkaline phosphatase increased
         subjects affected / exposed
    3 / 42 (7.14%)
    4 / 83 (4.82%)
    1 / 41 (2.44%)
         occurrences all number
    3
    4
    1
    Blood creatinine increased
         subjects affected / exposed
    4 / 42 (9.52%)
    7 / 83 (8.43%)
    3 / 41 (7.32%)
         occurrences all number
    4
    7
    3
    Lipase increased
         subjects affected / exposed
    5 / 42 (11.90%)
    7 / 83 (8.43%)
    2 / 41 (4.88%)
         occurrences all number
    10
    14
    4
    Weight decreased
         subjects affected / exposed
    4 / 42 (9.52%)
    4 / 83 (4.82%)
    0 / 41 (0.00%)
         occurrences all number
    4
    4
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    1 / 42 (2.38%)
    5 / 83 (6.02%)
    4 / 41 (9.76%)
         occurrences all number
    1
    5
    4
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    11 / 42 (26.19%)
    20 / 83 (24.10%)
    9 / 41 (21.95%)
         occurrences all number
    15
    24
    9
    Lymphopenia
         subjects affected / exposed
    3 / 42 (7.14%)
    5 / 83 (6.02%)
    2 / 41 (4.88%)
         occurrences all number
    3
    9
    6
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    4 / 42 (9.52%)
    11 / 83 (13.25%)
    7 / 41 (17.07%)
         occurrences all number
    5
    15
    10
    Chest pain
         subjects affected / exposed
    1 / 42 (2.38%)
    5 / 83 (6.02%)
    4 / 41 (9.76%)
         occurrences all number
    1
    5
    4
    Fatigue
         subjects affected / exposed
    13 / 42 (30.95%)
    18 / 83 (21.69%)
    5 / 41 (12.20%)
         occurrences all number
    13
    18
    5
    Oedema peripheral
         subjects affected / exposed
    3 / 42 (7.14%)
    4 / 83 (4.82%)
    1 / 41 (2.44%)
         occurrences all number
    3
    4
    1
    Pyrexia
         subjects affected / exposed
    7 / 42 (16.67%)
    10 / 83 (12.05%)
    3 / 41 (7.32%)
         occurrences all number
    7
    10
    3
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    6 / 42 (14.29%)
    8 / 83 (9.64%)
    2 / 41 (4.88%)
         occurrences all number
    7
    9
    2
    Constipation
         subjects affected / exposed
    14 / 42 (33.33%)
    20 / 83 (24.10%)
    6 / 41 (14.63%)
         occurrences all number
    16
    22
    6
    Diarrhoea
         subjects affected / exposed
    9 / 42 (21.43%)
    13 / 83 (15.66%)
    4 / 41 (9.76%)
         occurrences all number
    15
    20
    5
    Dry mouth
         subjects affected / exposed
    3 / 42 (7.14%)
    4 / 83 (4.82%)
    1 / 41 (2.44%)
         occurrences all number
    3
    5
    2
    Dyspepsia
         subjects affected / exposed
    3 / 42 (7.14%)
    3 / 83 (3.61%)
    0 / 41 (0.00%)
         occurrences all number
    3
    3
    0
    Nausea
         subjects affected / exposed
    10 / 42 (23.81%)
    16 / 83 (19.28%)
    6 / 41 (14.63%)
         occurrences all number
    12
    22
    10
    Vomiting
         subjects affected / exposed
    6 / 42 (14.29%)
    10 / 83 (12.05%)
    4 / 41 (9.76%)
         occurrences all number
    7
    14
    7
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    5 / 42 (11.90%)
    7 / 83 (8.43%)
    2 / 41 (4.88%)
         occurrences all number
    5
    7
    2
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    8 / 42 (19.05%)
    12 / 83 (14.46%)
    4 / 41 (9.76%)
         occurrences all number
    9
    16
    7
    Rash
         subjects affected / exposed
    9 / 42 (21.43%)
    13 / 83 (15.66%)
    4 / 41 (9.76%)
         occurrences all number
    11
    17
    6
    Rash maculo-papular
         subjects affected / exposed
    3 / 42 (7.14%)
    3 / 83 (3.61%)
    0 / 41 (0.00%)
         occurrences all number
    3
    3
    0
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    4 / 42 (9.52%)
    5 / 83 (6.02%)
    1 / 41 (2.44%)
         occurrences all number
    4
    5
    1
    Haematuria
         subjects affected / exposed
    8 / 42 (19.05%)
    11 / 83 (13.25%)
    3 / 41 (7.32%)
         occurrences all number
    9
    12
    3
    Renal impairment
         subjects affected / exposed
    4 / 42 (9.52%)
    5 / 83 (6.02%)
    1 / 41 (2.44%)
         occurrences all number
    4
    5
    1
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    4 / 42 (9.52%)
    5 / 83 (6.02%)
    1 / 41 (2.44%)
         occurrences all number
    4
    5
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    4 / 42 (9.52%)
    6 / 83 (7.23%)
    2 / 41 (4.88%)
         occurrences all number
    4
    7
    3
    Back pain
         subjects affected / exposed
    4 / 42 (9.52%)
    8 / 83 (9.64%)
    4 / 41 (9.76%)
         occurrences all number
    4
    9
    5
    Groin pain
         subjects affected / exposed
    4 / 42 (9.52%)
    4 / 83 (4.82%)
    0 / 41 (0.00%)
         occurrences all number
    4
    4
    0
    Musculoskeletal pain
         subjects affected / exposed
    4 / 42 (9.52%)
    6 / 83 (7.23%)
    2 / 41 (4.88%)
         occurrences all number
    5
    7
    2
    Infections and infestations
    Upper respiratory tract infection
         subjects affected / exposed
    3 / 42 (7.14%)
    3 / 83 (3.61%)
    0 / 41 (0.00%)
         occurrences all number
    4
    4
    0
    Urinary tract infection
         subjects affected / exposed
    7 / 42 (16.67%)
    13 / 83 (15.66%)
    6 / 41 (14.63%)
         occurrences all number
    13
    22
    9
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    13 / 42 (30.95%)
    19 / 83 (22.89%)
    6 / 41 (14.63%)
         occurrences all number
    15
    21
    6
    Hyperglycaemia
         subjects affected / exposed
    4 / 42 (9.52%)
    4 / 83 (4.82%)
    0 / 41 (0.00%)
         occurrences all number
    5
    5
    0
    Hypoalbuminaemia
         subjects affected / exposed
    3 / 42 (7.14%)
    4 / 83 (4.82%)
    1 / 41 (2.44%)
         occurrences all number
    3
    4
    1
    Hyponatraemia
         subjects affected / exposed
    3 / 42 (7.14%)
    3 / 83 (3.61%)
    0 / 41 (0.00%)
         occurrences all number
    3
    3
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    08 Dec 2017
    More frequent pregnancy testing and extend the prohibition of live vaccines to 3 months after the end of treatment
    08 Mar 2018
    To align HIV, pregnancy testing, and other modifications with regulatory requirements in Germany
    12 Jun 2018
    Enrollment was permanently stopped on 02May2018 as a strategic decision. For participants who are considered to be obtaining ongoing clinical benefit, continued study treatment will be at the discretion of the investigator after a discussion with the participant of the results from KEYNOTE-252/ECHO-301 study.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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