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Pembrolizumab Plus Epacadostat, Pembrolizumab Monotherapy, and the EXTREME Regimen in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (KEYNOTE-669/ECHO-304)

Sponsor
Incyte Corporation (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03358472
Collaborator
Merck Sharp & Dohme LLC (Industry)
89
Enrollment
73
Locations
3
Arms
66.7
Anticipated Duration (Months)
1.2
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study was to evaluate the efficacy and safety of pembrolizumab plus epacadostat, pembrolizumab monotherapy, and the EXTREME regimen (cetuximab + cisplatin or carboplatin + 5-fluorouracil) as first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
89 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 3 Randomized, Open-Label Clinical Study to Evaluate the Efficacy and Safety of Pembrolizumab Plus Epacadostat, Pembrolizumab Monotherapy, and the EXTREME Regimen as First Line Treatment for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (KEYNOTE-669/ECHO-304)
Actual Study Start Date :
Dec 1, 2017
Actual Primary Completion Date :
Jul 19, 2018
Anticipated Study Completion Date :
Jun 23, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Pembrolizumab + Epacadostat

Drug: Pembrolizumab
Pembrolizumab administered intravenously every 3 weeks.
Other Names:
  • MK-3475

    • Drug: Epacadostat
    Epacadostat administered orally twice daily.
    Other Names:
  • INCB024360

    		•
    Experimental: Pembrolizumab

    Drug: Pembrolizumab
    Pembrolizumab administered intravenously every 3 weeks.
    Other Names:
  • MK-3475

    		•
    Active Comparator: EXTREME

    EXTREME regimen includes cetuximab + cisplatin or carboplatin + 5-fluorouracil.

    Drug: Cetuximab
    Cetuximab administered intravenously on Cycle 1 Day 1 followed by administration every week.

    Drug: Cisplatin
    Cisplatin administered intravenously every 3 weeks for </= 6 cycles.

    Drug: Carboplatin
    Carboplatin administered intravenously every 3 weeks for </= 6 cycles.

    Drug: 5-Fluorouracil
    5-Fluorouracil administered intravenously every 3 weeks for </= 6 cycles.

    Outcome Measures

    Primary Outcome Measures

    1. Objective Response Rate (ORR) of Pembrolizumab + Epacadostat, Pembrolizumab Monotherapy and the EXTREME Regimen [Minimum Week 9]

      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. Responses are based on investigator assessments per RECIST 1.1 without confirmation using all available scans.

    Secondary Outcome Measures

    1. Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab Versus the EXTREME Regimen as Measured by Number of Participants Experiencing Adverse Events (AEs) [Up to 14 months]

      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. Data reported from start of study to data cutoff 17 Jan 2019, up to 14 months.

    2. Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab Versus the EXTREME Regimen as Measured by Number of Participants Discontinuing Study Treatment Due to AEs [Up to 14 months]

      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. Data reported from start of study to data cutoff 17 Jan 2019, up to 14 months.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Measurable disease based on RECIST v1.1.

    • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

    • Adequate organ function per protocol-defined criteria.

    • Documentation of results from testing of human papilloma virus (HPV) status for oropharyngeal cancer.

    • Baseline archival tumor specimen available or willing to undergo a prestudy treatment tumor core or excisional biopsy of a tumor lesion not previously irradiated, to obtain the specimen.

    Exclusion Criteria:

    • Carcinoma of the nasopharynx, salivary gland, unknown primary origin, or nonsquamous histologies as primary tumors.

    • Disease progression within 6 months of completion of curatively intended systemic treatment for locoregionally advanced HNSCC.

    • Use of protocol-defined prior/concomitant therapy.

    • Known additional malignancy that is progressing or has required active treatment within the past 3 years.

    • Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.

    • Active autoimmune disease that has required systemic treatment in past 2 years.

    • Known history of human immunodeficiency virus (HIV) infection. HIV testing is not required unless mandated by local health authority.

    • Known history of or is positive for active hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (defined as HCV RNA [qualitative] is detected).

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Pacific Cancer Medical Center Anaheim California United States 19026
    2 UC Davis Comprehensive Cancer Center Sacramento California United States 95817
    3 St. Joseph Heritage Healthcare Santa Rosa California United States 95403
    4 University of Colorado Cancer Center Aurora Colorado United States 80045
    5 Yale Cancer Center New Haven Connecticut United States 06520
    6 Northwest Georgia Oncology Centers PC Douglasville Georgia United States 30134
    7 U of Kansas Cancer Center Westwood Kansas United States 66205
    8 Baptist Health Louisville Kentucky United States 40223
    9 St. Vincent Healthcare Cancer Ctr Billings Montana United States 59102
    10 New Mexico Cancer Care Alliance Albuquerque New Mexico United States 87106
    11 Oklahoma Cancer Specialists and Research Tulsa Oklahoma United States 74146
    12 Providence Portland Med Center Portland Oregon United States 97213
    13 Huntsman Cancer Institute Univ of Utah Salt Lake City Utah United States 19026
    14 Viginia Mason Med Ctr Seattle Washington United States 98101
    15 Chris OBrien Lifehouse Camperdown New South Wales Australia 2050
    16 Macquarie University Hospital North Ryde New South Wales Australia 2109
    17 Royal Brisbane & Women s Hospital Herston Queensland Australia 4029
    18 Landeskrankenhaus Salzburg Salzburg Austria 5020
    19 Allgemeines Krankenhaus der Stadt Wien Wien Austria 1090
    20 Juravinski Cancer Center Hamilton Health Sciences Hamilton Ontario Canada L8V 5C2
    21 Princess Margaret Cancer Centre Toronto Ontario Canada M5G 2M9
    22 Jewish General Hospital Montreal Quebec Canada H3T 1E2
    23 CHU de Quebec-Universite Laval-Hotel Dieu de Quebec Quebec Canada G1R 3S1
    24 Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz Miskolc Hungary 3526
    25 Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet Szolnok Hungary 5000
    26 Istituto Europeo di Oncologia Milano Italy 20141
    27 IRRCS Instituto Clinico Humanitas Rozzano Italy 20089
    28 National Cancer Center Hospital East Kashiwa Chiba Japan 277-8577
    29 Kanazawa University Hospital Kanazawa Ishikawa Japan 920-8641
    30 Kanagawa Cancer Center Yokohama Kanagawa Japan 241-8515
    31 Miyagi Cancer Center Natori Miyagi Japan 981-1293
    32 Tohoku University Hospital Sendai Miyagi Japan 980-8574
    33 Hyogo Cancer Center Akashi Japan 673-8558
    34 Kyushu University Hospital Fukuoka Japan 812-8582
    35 Hiroshima University Hospital Hiroshima Japan 734-8551
    36 Hokkaido University Hospital Hokkaido Japan 060-8648
    37 Kobe City Medical Center General Hospital Kobe Japan 650-0047
    38 Kindai University Hospital Osakasayama City Japan 589-8511
    39 Saitama Cancer Center Saitama Japan 362-0806
    40 Shizuoka Cancer Center Hospital and Research Institute Shizuoka Japan 411-8777
    41 The Cancer Institute Hospital of JFCR Tokyo Japan 135-8550
    42 Seoul National University Hospital Seoul Korea, Republic of 03080
    43 Severance Hospital Yonsei University Health System Seoul Korea, Republic of 03722
    44 Asan Medical Center Seoul Korea, Republic of 05505
    45 Mazowiecki Szpital Onkologiczny Wieliszew Mazowieckie Poland 05-135
    46 Przychodnia Lekarska Komed Konin Poland 62-500
    47 Zachodniopomorskie Centrum Onkologii Szczecin Poland 71-730
    48 Inst. Portugues de Oncologia de Coimbra Frencisco Gentil EPE Coimbra Portugal 3000-075
    49 Inst. Portugues de Oncologia de Lisboa Francisco Gentil EPE Lisboa Portugal 1099-023
    50 Centro Hospitalar Lisboa Norte EPE - Hospital de Santa Maria Lisboa Portugal 1649-035
    51 Inst. Portugues de Oncologia de Porto Francisco Gentil EPE Porto Portugal 4200-072
    52 Hospital Germans Trias i Pujol. ICO de Badalona Badalona Spain 08916
    53 Hospital General Universitari Vall d Hebron Barcelona Spain 08035
    54 Hospital Ramon y Cajal Madrid Spain 28034
    55 Hospital Universitario 12 de Octubre Madrid Spain 28041
    56 Hospital Infanta Cristina Madrid Spain 28981
    57 Hospital de Nuestra Senora de Valme Sevilla Spain 41014
    58 Hospital Clinico Lozano Blesa Zaragoza Spain 50009
    59 National Cheng Kung University Hospital Tainan Taiwan 70457
    60 National Taiwan University Hospital Taipei Taiwan 10048
    61 Chang Gung Medical Foundation. Linkou Taoyuan Taiwan 33305
    62 Adana Sehir Hastanesi Adana Turkey 01370
    63 Hacettepe Universitesi Tip Fakultesi Hastanesi Ankara Turkey 06100
    64 Trakya Universitesi Tip Fakultesi Edirne Turkey 22030
    65 Istanbul Universitesi Onkoloji Enstitusu Istanbul Turkey 34093
    66 Medipol Hastanesi Istanbul Turkey 34214
    67 Ege Universitesi Tip Fakultesi Hastanesi Izmir Turkey 35040
    68 Inonu Universitesi Turgut Ozal Tip Merkezi Malatya Turkey 44280
    69 North Middlesex Hospital London United Kingdom N18 1QX
    70 University College London Hospitals (UCLH) London United Kingdom NW1 2PG
    71 The Royal Marsden Foundation Trust London United Kingdom SW3 6JJ
    72 The Royal Marsden Nhs Foundation Trust - Chelsea London United Kingdom SW3 6JJ
    73 Musgrove Park Hospital Taunton United Kingdom TA1 5DA

    Sponsors and Collaborators

    • Incyte Corporation
    • Merck Sharp & Dohme LLC

    Investigators

    • Study Director: Mark Jones, MD, Incyte Corporation

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Incyte Corporation
    ClinicalTrials.gov Identifier:
    NCT03358472
    Other Study ID Numbers:
    • KEYNOTE-669/ECHO 304
    First Posted:
    Nov 30, 2017
    Last Update Posted:
    Aug 2, 2022
    Last Verified:
    Jul 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Incyte Corporation
    Head and neck squamous cell carcinoma
    programmed cell death 1 (PD-1) inhibitor
    indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor
    Additional relevant MeSH terms:
    Carcinoma
    Carcinoma, Squamous Cell
    Squamous Cell Carcinoma of Head and Neck
    Carboplatin
    Pembrolizumab
    Fluorouracil
    Cetuximab

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail This study was conducted at 76 centers in 14 countries.
    Arm/Group Title Pembrolizumab + Epacadostat Pembrolizumab EXTREME
    Arm/Group Description Pembrolizumab administered intravenously every 3 weeks. Epacadostat administered orally twice daily. Pembrolizumab administered intravenously every 3 weeks. EXTREME regimen includes cetuximab + cisplatin or carboplatin + 5-fluorouracil. Cetuximab administered intravenously on Cycle 1 Day 1 followed by administration every week. Cisplatin administered intravenously every 3 weeks for </= 6 cycles. Carboplatin administered intravenously every 3 weeks for </= 6 cycles. 5-Fluorouracil administered intravenously every 3 weeks for </= 6 cycles.
    Period Title: Overall Study
    STARTED 35 19 35
    Intention-to-Treat (ITT) 35 19 35
    All Participants as Treated (APaT) 34 19 34
    COMPLETED 20 9 19
    NOT COMPLETED 15 10 16

    Baseline Characteristics

    Arm/Group Title Pembrolizumab + Epacadostat Pembrolizumab EXTREME Total
    Arm/Group Description Pembrolizumab administered intravenously every 3 weeks. Epacadostat administered orally twice daily. Pembrolizumab administered intravenously every 3 weeks. EXTREME regimen includes cetuximab + cisplatin or carboplatin + 5-fluorouracil. Cetuximab administered intravenously on Cycle 1 Day 1 followed by administration every week. Cisplatin administered intravenously every 3 weeks for </= 6 cycles. Carboplatin administered intravenously every 3 weeks for </= 6 cycles. 5-Fluorouracil administered intravenously every 3 weeks for </= 6 cycles. Total of all reporting groups
    Overall Participants 35 19 35 89
    Age, Customized (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    62.1
    (9.0)
    63.0
    (9.6)
    62.7
    (10.0)
    62.5
    (9.4)
    Sex: Female, Male (Count of Participants)
    Female
    5
    14.3%
    3
    15.8%
    6
    17.1%
    14
    15.7%
    Male
    30
    85.7%
    16
    84.2%
    29
    82.9%
    75
    84.3%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Not Hispanic or Latino
    34
    97.1%
    17
    89.5%
    35
    100%
    86
    96.6%
    Unknown or Not Reported
    1
    2.9%
    2
    10.5%
    0
    0%
    3
    3.4%
    Race/Ethnicity, Customized (Count of Participants)
    Asian
    6
    17.1%
    5
    26.3%
    13
    37.1%
    24
    27%
    Black Or African American
    1
    2.9%
    0
    0%
    0
    0%
    1
    1.1%
    White
    28
    80%
    14
    73.7%
    22
    62.9%
    64
    71.9%
    Primary Tumor Site (Count of Participants)
    Oropharynx
    12
    34.3%
    6
    31.6%
    12
    34.3%
    30
    33.7%
    Oral Cavity
    10
    28.6%
    5
    26.3%
    7
    20%
    22
    24.7%
    Larynx
    9
    25.7%
    5
    26.3%
    7
    20%
    21
    23.6%
    Hypopharynx
    4
    11.4%
    3
    15.8%
    9
    25.7%
    16
    18%

    Outcome Measures

    1. Primary Outcome
    Title Objective Response Rate (ORR) of Pembrolizumab + Epacadostat, Pembrolizumab Monotherapy and the EXTREME Regimen
    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. Responses are based on investigator assessments per RECIST 1.1 without confirmation using all available scans.
    Time Frame Minimum Week 9

    Outcome Measure Data

    Analysis Population Description
    The Intention-to-Treat (ITT) population consisted of all randomized participants. The ORR was based on all available imaging assessments after the last participant completed the Week 9 imaging assessment by investigator determination.
    Arm/Group Title Pembrolizumab + Epacadostat Pembrolizumab EXTREME
    Arm/Group Description Pembrolizumab administered intravenously every 3 weeks. Epacadostat administered orally twice daily. Pembrolizumab administered intravenously every 3 weeks. EXTREME regimen includes cetuximab + cisplatin or carboplatin + 5-fluorouracil. Cetuximab administered intravenously on Cycle 1 Day 1 followed by administration every week. Cisplatin administered intravenously every 3 weeks for </= 6 cycles. Carboplatin administered intravenously every 3 weeks for </= 6 cycles. 5-Fluorouracil administered intravenously every 3 weeks for </= 6 cycles.
    Measure Participants 35 19 35
    Number (95% Confidence Interval) [percentage of participants]
    31.4
    89.7%
    21.1
    111.1%
    34.3
    98%
    2. Secondary Outcome
    Title Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab Versus the EXTREME Regimen as Measured by Number of Participants Experiencing Adverse Events (AEs)
    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. Data reported from start of study to data cutoff 17 Jan 2019, up to 14 months.
    Time Frame Up to 14 months

    Outcome Measure Data

    Analysis Population Description
    All Participants as Treated (APaT) population consisted of all randomized participants who received at least 1 dose of study treatment.
    Arm/Group Title Pembrolizumab + Epacadostat Pembrolizumab EXTREME
    Arm/Group Description Pembrolizumab administered intravenously every 3 weeks. Epacadostat administered orally twice daily. Pembrolizumab administered intravenously every 3 weeks. EXTREME regimen includes cetuximab + cisplatin or carboplatin + 5-fluorouracil. Cetuximab administered intravenously on Cycle 1 Day 1 followed by administration every week. Cisplatin administered intravenously every 3 weeks for </= 6 cycles. Carboplatin administered intravenously every 3 weeks for </= 6 cycles. 5-Fluorouracil administered intravenously every 3 weeks for </= 6 cycles.
    Measure Participants 34 19 34
    Count of Participants [Participants]
    34
    97.1%
    17
    89.5%
    34
    97.1%
    3. Secondary Outcome
    Title Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab Versus the EXTREME Regimen as Measured by Number of Participants Discontinuing Study Treatment Due to AEs
    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. Data reported from start of study to data cutoff 17 Jan 2019, up to 14 months.
    Time Frame Up to 14 months

    Outcome Measure Data

    Analysis Population Description
    All Participants as Treated (APaT) population consisted of all randomized participants who received at least 1 dose of study treatment.
    Arm/Group Title Pembrolizumab + Epacadostat Pembrolizumab EXTREME
    Arm/Group Description Pembrolizumab administered intravenously every 3 weeks. Epacadostat administered orally twice daily. Pembrolizumab administered intravenously every 3 weeks. EXTREME regimen includes cetuximab + cisplatin or carboplatin + 5-fluorouracil. Cetuximab administered intravenously on Cycle 1 Day 1 followed by administration every week. Cisplatin administered intravenously every 3 weeks for </= 6 cycles. Carboplatin administered intravenously every 3 weeks for </= 6 cycles. 5-Fluorouracil administered intravenously every 3 weeks for </= 6 cycles.
    Measure Participants 34 19 34
    Count of Participants [Participants]
    3
    8.6%
    2
    10.5%
    7
    20%

    Adverse Events

    Time Frame Non-serious adverse events were reported from start of study, up to 30 days after last dose and serious adverse events up to 90 days after last dose are included, up to 14 months
    Adverse Event Reporting Description The All Participants as Treated (APaT) population was used for the safety analysis and consisted of all randomized participants who received at least 1 dose of study treatment. All-Cause Mortality was based on the ITT population and consisted of all randomized participants. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to the drug are excluded
    Arm/Group Title Pembrolizumab + Epacadostat Pembrolizumab EXTREME
    Arm/Group Description Pembrolizumab administered intravenously every 3 weeks. Epacadostat administered orally twice daily. Pembrolizumab administered intravenously every 3 weeks. EXTREME regimen includes cetuximab + cisplatin or carboplatin + 5-fluorouracil. Cetuximab administered intravenously on Cycle 1 Day 1 followed by administration every week. Cisplatin administered intravenously every 3 weeks for </= 6 cycles. Carboplatin administered intravenously every 3 weeks for </= 6 cycles. 5-Fluorouracil administered intravenously every 3 weeks for </= 6 cycles.
    All Cause Mortality
    Pembrolizumab + Epacadostat Pembrolizumab EXTREME
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 6/35 (17.1%) 4/19 (21.1%) 10/35 (28.6%)
    Serious Adverse Events
    Pembrolizumab + Epacadostat Pembrolizumab EXTREME
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 12/34 (35.3%) 8/19 (42.1%) 12/34 (35.3%)
    Blood and lymphatic system disorders
    Febrile neutropenia 0/34 (0%) 0/19 (0%) 2/34 (5.9%)
    Cardiac disorders
    Atrioventricular block complete 0/34 (0%) 1/19 (5.3%) 0/34 (0%)
    Myocardial infarction 0/34 (0%) 1/19 (5.3%) 0/34 (0%)
    Gastrointestinal disorders
    Colitis 1/34 (2.9%) 0/19 (0%) 0/34 (0%)
    Diarrhoea 0/34 (0%) 1/19 (5.3%) 0/34 (0%)
    Duodenal ulcer 0/34 (0%) 0/19 (0%) 1/34 (2.9%)
    Intestinal obstruction 0/34 (0%) 0/19 (0%) 1/34 (2.9%)
    Nausea 1/34 (2.9%) 0/19 (0%) 0/34 (0%)
    General disorders
    Localised oedema 0/34 (0%) 0/19 (0%) 1/34 (2.9%)
    Oedema 1/34 (2.9%) 0/19 (0%) 0/34 (0%)
    Hepatobiliary disorders
    Cholangitis 0/34 (0%) 1/19 (5.3%) 1/34 (2.9%)
    Hepatic function abnormal 0/34 (0%) 1/19 (5.3%) 0/34 (0%)
    Hepatitis 1/34 (2.9%) 0/19 (0%) 0/34 (0%)
    Infections and infestations
    Bacterial infection 0/34 (0%) 1/19 (5.3%) 0/34 (0%)
    Catheter site infection 0/34 (0%) 0/19 (0%) 1/34 (2.9%)
    Cellulitis 1/34 (2.9%) 0/19 (0%) 1/34 (2.9%)
    Clostridial sepsis 0/34 (0%) 0/19 (0%) 1/34 (2.9%)
    Empyema 0/34 (0%) 1/19 (5.3%) 0/34 (0%)
    Lower respiratory tract infection 1/34 (2.9%) 0/19 (0%) 0/34 (0%)
    Lung infection 1/34 (2.9%) 0/19 (0%) 0/34 (0%)
    Osteomyelitis 1/34 (2.9%) 0/19 (0%) 0/34 (0%)
    Pneumonia 1/34 (2.9%) 0/19 (0%) 1/34 (2.9%)
    Sepsis 0/34 (0%) 0/19 (0%) 1/34 (2.9%)
    Injury, poisoning and procedural complications
    Post procedural haemorrhage 0/34 (0%) 0/19 (0%) 1/34 (2.9%)
    Traumatic haemothorax 0/34 (0%) 1/19 (5.3%) 0/34 (0%)
    Investigations
    Blood creatinine increased 0/34 (0%) 0/19 (0%) 1/34 (2.9%)
    Metabolism and nutrition disorders
    Hypercalcaemia 0/34 (0%) 0/19 (0%) 1/34 (2.9%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer pain 1/34 (2.9%) 0/19 (0%) 0/34 (0%)
    Tumour haemorrhage 1/34 (2.9%) 1/19 (5.3%) 0/34 (0%)
    Nervous system disorders
    Cerebral infarction 0/34 (0%) 0/19 (0%) 1/34 (2.9%)
    Cerebral ischaemia 0/34 (0%) 1/19 (5.3%) 0/34 (0%)
    Syncope 1/34 (2.9%) 0/19 (0%) 0/34 (0%)
    Renal and urinary disorders
    Acute kidney injury 1/34 (2.9%) 0/19 (0%) 0/34 (0%)
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure 0/34 (0%) 0/19 (0%) 1/34 (2.9%)
    Epistaxis 1/34 (2.9%) 0/19 (0%) 0/34 (0%)
    Haemoptysis 0/34 (0%) 1/19 (5.3%) 0/34 (0%)
    Pneumonia aspiration 1/34 (2.9%) 0/19 (0%) 1/34 (2.9%)
    Pneumonitis 2/34 (5.9%) 0/19 (0%) 0/34 (0%)
    Other (Not Including Serious) Adverse Events
    Pembrolizumab + Epacadostat Pembrolizumab EXTREME
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 34/34 (100%) 17/19 (89.5%) 34/34 (100%)
    Blood and lymphatic system disorders
    Anaemia 5/34 (14.7%) 4/19 (21.1%) 19/34 (55.9%)
    Leukocytosis 2/34 (5.9%) 0/19 (0%) 0/34 (0%)
    Leukopenia 1/34 (2.9%) 0/19 (0%) 3/34 (8.8%)
    Neutropenia 0/34 (0%) 0/19 (0%) 13/34 (38.2%)
    Thrombocytopenia 0/34 (0%) 0/19 (0%) 9/34 (26.5%)
    Cardiac disorders
    Pericardial effusion 0/34 (0%) 1/19 (5.3%) 0/34 (0%)
    Endocrine disorders
    Hyperthyroidism 1/34 (2.9%) 1/19 (5.3%) 0/34 (0%)
    Hypothyroidism 6/34 (17.6%) 4/19 (21.1%) 1/34 (2.9%)
    Eye disorders
    Eyelid oedema 0/34 (0%) 1/19 (5.3%) 0/34 (0%)
    Lacrimation increased 0/34 (0%) 1/19 (5.3%) 0/34 (0%)
    Gastrointestinal disorders
    Abdominal pain 2/34 (5.9%) 0/19 (0%) 0/34 (0%)
    Abdominal pain upper 3/34 (8.8%) 0/19 (0%) 1/34 (2.9%)
    Ankyloglossia acquired 0/34 (0%) 1/19 (5.3%) 0/34 (0%)
    Cheilosis 0/34 (0%) 1/19 (5.3%) 0/34 (0%)
    Constipation 6/34 (17.6%) 1/19 (5.3%) 12/34 (35.3%)
    Diarrhoea 7/34 (20.6%) 2/19 (10.5%) 7/34 (20.6%)
    Dry mouth 0/34 (0%) 1/19 (5.3%) 1/34 (2.9%)
    Dyspepsia 3/34 (8.8%) 0/19 (0%) 2/34 (5.9%)
    Dysphagia 1/34 (2.9%) 0/19 (0%) 3/34 (8.8%)
    Gastrooesophageal reflux disease 2/34 (5.9%) 0/19 (0%) 1/34 (2.9%)
    Nausea 5/34 (14.7%) 2/19 (10.5%) 17/34 (50%)
    Odynophagia 2/34 (5.9%) 0/19 (0%) 0/34 (0%)
    Oral pain 2/34 (5.9%) 1/19 (5.3%) 0/34 (0%)
    Salivary hypersecretion 0/34 (0%) 1/19 (5.3%) 1/34 (2.9%)
    Stomatitis 3/34 (8.8%) 0/19 (0%) 8/34 (23.5%)
    Vomiting 7/34 (20.6%) 0/19 (0%) 5/34 (14.7%)
    General disorders
    Asthenia 6/34 (17.6%) 2/19 (10.5%) 8/34 (23.5%)
    Chest pain 2/34 (5.9%) 2/19 (10.5%) 2/34 (5.9%)
    Face oedema 2/34 (5.9%) 1/19 (5.3%) 0/34 (0%)
    Fatigue 11/34 (32.4%) 3/19 (15.8%) 7/34 (20.6%)
    Malaise 0/34 (0%) 0/19 (0%) 3/34 (8.8%)
    Mucosal inflammation 0/34 (0%) 0/19 (0%) 10/34 (29.4%)
    Oedema peripheral 1/34 (2.9%) 1/19 (5.3%) 1/34 (2.9%)
    Pyrexia 3/34 (8.8%) 0/19 (0%) 5/34 (14.7%)
    Swelling 1/34 (2.9%) 1/19 (5.3%) 1/34 (2.9%)
    Ulcer 0/34 (0%) 1/19 (5.3%) 0/34 (0%)
    Hepatobiliary disorders
    Hepatotoxicity 0/34 (0%) 0/19 (0%) 2/34 (5.9%)
    Infections and infestations
    Bronchitis 0/34 (0%) 1/19 (5.3%) 0/34 (0%)
    Conjunctivitis 0/34 (0%) 0/19 (0%) 3/34 (8.8%)
    Device related infection 0/34 (0%) 0/19 (0%) 2/34 (5.9%)
    Cellulitis 0/34 (0%) 1/19 (5.3%) 0/34 (0%)
    Nasopharyngitis 0/34 (0%) 3/19 (15.8%) 3/34 (8.8%)
    Oral candidiasis 1/34 (2.9%) 0/19 (0%) 3/34 (8.8%)
    Paronychia 0/34 (0%) 0/19 (0%) 9/34 (26.5%)
    Pneumonia 2/34 (5.9%) 0/19 (0%) 0/34 (0%)
    Respiratory tract infection 2/34 (5.9%) 0/19 (0%) 1/34 (2.9%)
    Urinary tract infection 0/34 (0%) 1/19 (5.3%) 0/34 (0%)
    Wound infection 0/34 (0%) 1/19 (5.3%) 0/34 (0%)
    Investigations
    Alanine aminotransferase increased 2/34 (5.9%) 1/19 (5.3%) 5/34 (14.7%)
    Amylase increased 4/34 (11.8%) 1/19 (5.3%) 2/34 (5.9%)
    Aspartate aminotransferase increased 3/34 (8.8%) 1/19 (5.3%) 4/34 (11.8%)
    Blood alkaline phosphatase increased 0/34 (0%) 2/19 (10.5%) 1/34 (2.9%)
    Blood bilirubin increased 0/34 (0%) 1/19 (5.3%) 0/34 (0%)
    Blood creatinine increased 3/34 (8.8%) 1/19 (5.3%) 3/34 (8.8%)
    Blood glucose increased 0/34 (0%) 1/19 (5.3%) 0/34 (0%)
    Blood potassium decreased 0/34 (0%) 0/19 (0%) 2/34 (5.9%)
    Blood sodium decreased 0/34 (0%) 1/19 (5.3%) 0/34 (0%)
    Blood thyroid stimulating hormone increased 0/34 (0%) 1/19 (5.3%) 1/34 (2.9%)
    Gamma-glutamyltransferase increased 0/34 (0%) 1/19 (5.3%) 1/34 (2.9%)
    Lipase increased 6/34 (17.6%) 0/19 (0%) 4/34 (11.8%)
    Lymphocyte count decreased 0/34 (0%) 1/19 (5.3%) 1/34 (2.9%)
    Neutrophil count decreased 1/34 (2.9%) 0/19 (0%) 8/34 (23.5%)
    Platelet count decreased 0/34 (0%) 0/19 (0%) 12/34 (35.3%)
    Weight decreased 3/34 (8.8%) 2/19 (10.5%) 8/34 (23.5%)
    White blood cell count decreased 0/34 (0%) 0/19 (0%) 7/34 (20.6%)
    Metabolism and nutrition disorders
    Cachexia 0/34 (0%) 1/19 (5.3%) 1/34 (2.9%)
    Decreased appetite 3/34 (8.8%) 2/19 (10.5%) 9/34 (26.5%)
    Hypercalcaemia 2/34 (5.9%) 0/19 (0%) 3/34 (8.8%)
    Hyperglycaemia 0/34 (0%) 2/19 (10.5%) 1/34 (2.9%)
    Hyperkalaemia 2/34 (5.9%) 0/19 (0%) 1/34 (2.9%)
    Hypoalbuminaemia 1/34 (2.9%) 1/19 (5.3%) 2/34 (5.9%)
    Hypocalcaemia 1/34 (2.9%) 1/19 (5.3%) 2/34 (5.9%)
    Hypokalaemia 1/34 (2.9%) 0/19 (0%) 4/34 (11.8%)
    Hypomagnesaemia 2/34 (5.9%) 0/19 (0%) 9/34 (26.5%)
    Hyponatraemia 2/34 (5.9%) 0/19 (0%) 0/34 (0%)
    Hypophosphataemia 2/34 (5.9%) 2/19 (10.5%) 2/34 (5.9%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/34 (2.9%) 2/19 (10.5%) 1/34 (2.9%)
    Back pain 4/34 (11.8%) 0/19 (0%) 2/34 (5.9%)
    Fistula 1/34 (2.9%) 1/19 (5.3%) 0/34 (0%)
    Muscle spasms 0/34 (0%) 1/19 (5.3%) 0/34 (0%)
    Musculoskeletal pain 0/34 (0%) 1/19 (5.3%) 3/34 (8.8%)
    Myalgia 1/34 (2.9%) 1/19 (5.3%) 0/34 (0%)
    Neck pain 1/34 (2.9%) 0/19 (0%) 3/34 (8.8%)
    Pain in extremity 2/34 (5.9%) 2/19 (10.5%) 1/34 (2.9%)
    Trismus 0/34 (0%) 1/19 (5.3%) 0/34 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer pain 1/34 (2.9%) 1/19 (5.3%) 1/34 (2.9%)
    Nervous system disorders
    Aphonia 0/34 (0%) 1/19 (5.3%) 0/34 (0%)
    Dizziness 2/34 (5.9%) 0/19 (0%) 1/34 (2.9%)
    Dysgeusia 0/34 (0%) 0/19 (0%) 4/34 (11.8%)
    Headache 3/34 (8.8%) 2/19 (10.5%) 1/34 (2.9%)
    Neuropathy peripheral 0/34 (0%) 0/19 (0%) 2/34 (5.9%)
    Tremor 0/34 (0%) 1/19 (5.3%) 0/34 (0%)
    Psychiatric disorders
    Anxiety 1/34 (2.9%) 1/19 (5.3%) 0/34 (0%)
    Confusional state 1/34 (2.9%) 0/19 (0%) 2/34 (5.9%)
    Insomnia 5/34 (14.7%) 0/19 (0%) 0/34 (0%)
    Renal and urinary disorders
    Glycosuria 0/34 (0%) 1/19 (5.3%) 0/34 (0%)
    Urinary tract disorder 0/34 (0%) 1/19 (5.3%) 0/34 (0%)
    Reproductive system and breast disorders
    Gynaecomastia 2/34 (5.9%) 0/19 (0%) 0/34 (0%)
    Respiratory, thoracic and mediastinal disorders
    Aspiration 0/34 (0%) 1/19 (5.3%) 0/34 (0%)
    Cough 3/34 (8.8%) 3/19 (15.8%) 1/34 (2.9%)
    Dysphonia 3/34 (8.8%) 1/19 (5.3%) 0/34 (0%)
    Dyspnoea 6/34 (17.6%) 1/19 (5.3%) 2/34 (5.9%)
    Haemoptysis 4/34 (11.8%) 0/19 (0%) 1/34 (2.9%)
    Hiccups 0/34 (0%) 1/19 (5.3%) 3/34 (8.8%)
    Nasal congestion 0/34 (0%) 1/19 (5.3%) 0/34 (0%)
    Oropharyngeal pain 2/34 (5.9%) 1/19 (5.3%) 1/34 (2.9%)
    Pharyngeal oedema 2/34 (5.9%) 0/19 (0%) 0/34 (0%)
    Productive cough 1/34 (2.9%) 0/19 (0%) 2/34 (5.9%)
    Pulmonary embolism 0/34 (0%) 1/19 (5.3%) 1/34 (2.9%)
    Rhinitis allergic 2/34 (5.9%) 0/19 (0%) 0/34 (0%)
    Tracheal oedema 0/34 (0%) 1/19 (5.3%) 0/34 (0%)
    Wheezing 2/34 (5.9%) 0/19 (0%) 0/34 (0%)
    Skin and subcutaneous tissue disorders
    Acne 0/34 (0%) 0/19 (0%) 2/34 (5.9%)
    Alopecia 0/34 (0%) 0/19 (0%) 2/34 (5.9%)
    Dermatitis acneiform 0/34 (0%) 0/19 (0%) 14/34 (41.2%)
    Erythema 2/34 (5.9%) 0/19 (0%) 1/34 (2.9%)
    Palmar-plantar erythrodysaesthesia syndrome 0/34 (0%) 0/19 (0%) 2/34 (5.9%)
    Pruritus 7/34 (20.6%) 0/19 (0%) 6/34 (17.6%)
    Rash 9/34 (26.5%) 4/19 (21.1%) 13/34 (38.2%)
    Skin fissures 0/34 (0%) 0/19 (0%) 3/34 (8.8%)
    Skin haemorrhage 0/34 (0%) 1/19 (5.3%) 0/34 (0%)
    Skin lesion 0/34 (0%) 2/19 (10.5%) 0/34 (0%)
    Urticaria 0/34 (0%) 1/19 (5.3%) 0/34 (0%)
    Vascular disorders
    Circulatory collapse 0/34 (0%) 1/19 (5.3%) 0/34 (0%)
    Hypertension 1/34 (2.9%) 2/19 (10.5%) 3/34 (8.8%)
    Hypotension 2/34 (5.9%) 0/19 (0%) 1/34 (2.9%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Following the first publication, the Institution and/or Principal Investigator may publish data or results from the Study, provided, however, that the Institution and/or Principal Investigator submits the proposed publication to the Sponsor for review at least sixty (60) days prior to the date of the proposed publication. Sponsor may remove from the proposed publication any information that is considered confidential and/or proprietary other than Study data and results.

    Results Point of Contact

    Name/Title Study Director
    Organization Incyte Corporation
    Phone 855-463-3463
    Email medinfo@incyte.com
    Responsible Party:
    Incyte Corporation
    ClinicalTrials.gov Identifier:
    NCT03358472
    Other Study ID Numbers:
    • KEYNOTE-669/ECHO 304
    First Posted:
    Nov 30, 2017
    Last Update Posted:
    Aug 2, 2022
    Last Verified:
    Jul 1, 2022