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    Summary
    EudraCT Number:2016-004678-16
    Sponsor's Protocol Code Number:INCB24360-207
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2018-03-19
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedSpain - AEMPS
    A.2EudraCT number2016-004678-16
    A.3Full title of the trial
    A Phase 1/2, Open-Label, Safety, Tolerability, and Efficacy Study of Epacadostat in Combination With Pembrolizumab and Chemotherapy in Subjects With Advanced or Metastatic Solid Tumors
    Estudio de fase I/II sin enmascaramiento sobre la seguridad, la tolerabilidad y la eficacia de epacadostat en combinación con pembrolizumab y quimioterapia en pacientes con tumores sólidos avanzados o metastásicos (ECHO-207/KEYNOTE-723)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase 1/2 Study of Epacadostat in Combination With Pembrolizumab and Chemotherapy in Subjects With Advanced or Metastatic Solid Tumors
    Estudio de fase I/II de epacadostat en combinación con pembrolizumab y quimioterapia en pacientes con tumores sólidos avanzados o metastásicos
    A.3.2Name or abbreviated title of the trial where available
    ECHO 207
    A.4.1Sponsor's protocol code numberINCB24360-207
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorIncyte Corporation
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportIncyte Corporation
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationIncyte Biosciences UK Ltd
    B.5.2Functional name of contact pointCarol Penning
    B.5.3 Address:
    B.5.3.1Street AddressRiverbridge House, Guildford Road
    B.5.3.2Town/ cityLeatherhead
    B.5.3.3Post codeKT22 9AD
    B.5.3.4CountryUnited States
    B.5.4Telephone number0013024252734
    B.5.6E-mailcpenning@incyte.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameEpacadostat
    D.3.2Product code INCB024360
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNEPACADOSTAT
    D.3.9.2Current sponsor codeINCB024360
    D.3.9.4EV Substance CodeSUB182018
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number25 to 100
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name KEYTRUDA
    D.2.1.1.2Name of the Marketing Authorisation holderMerck Sharp Dohme Limited
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namePembrolizumab
    D.3.2Product code MK-3475
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPEMBROLIZUMAB
    D.3.9.1CAS number 1374853-91-4
    D.3.9.2Current sponsor codeMK-3475
    D.3.9.4EV Substance CodeSUB167136
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 3
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.2Name of the Marketing Authorisation holderAccord Healthcare Limited
    D.2.1.2Country which granted the Marketing AuthorisationLatvia
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameOxaliplatin
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNOXALIPLATIN
    D.3.9.1CAS number 61825-94-3
    D.3.9.4EV Substance CodeSUB09490MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 4
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.2Name of the Marketing Authorisation holderTeva UK Limited
    D.2.1.2Country which granted the Marketing AuthorisationPoland
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameCalcium Folinate
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCALCIUM FOLINATE
    D.3.9.3Other descriptive nameCALCIUM FOLINATE
    D.3.9.4EV Substance CodeSUB06052MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 5
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.2Name of the Marketing Authorisation holderHospira UK Limited
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product name5-fluorouracil
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INN5-Fluorouracil
    D.3.9.3Other descriptive nameFLUOROURACIL
    D.3.9.4EV Substance CodeSUB07721MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/l milligram(s)/litre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 6
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Abraxane
    D.2.1.1.2Name of the Marketing Authorisation holderCelgene Europe Limited
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namenab-Paclitaxel
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPACLITAXEL
    D.3.9.1CAS number 33069-62-4
    D.3.9.4EV Substance CodeSUB09583MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 7
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.2Name of the Marketing Authorisation holderSun Pharmaceutical Industries Europe B.V.
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameGemcitabine
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNGEMCITABINE
    D.3.9.1CAS number 95058-81-4
    D.3.9.4EV Substance CodeSUB07892MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1000
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 8
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.2Name of the Marketing Authorisation holderAccord Healthcare Limited
    D.2.1.2Country which granted the Marketing AuthorisationPoland
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameCarboplatin
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCarboplatin
    D.3.9.3Other descriptive nameCARBOPLATIN
    D.3.9.4EV Substance CodeSUB06614MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 9
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.2Name of the Marketing Authorisation holderHospira UK Limited
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namePaclitaxel
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPACLITAXEL
    D.3.9.1CAS number 33069-62-4
    D.3.9.4EV Substance CodeSUB09583MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number6
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 10
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name ALIMTA
    D.2.1.1.2Name of the Marketing Authorisation holderEli Lilly Nederland B.V.
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namePemetrexed
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPEMETREXED
    D.3.9.1CAS number 137281-23-3
    D.3.9.4EV Substance CodeSUB09655MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number100 to 500
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 11
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.2Name of the Marketing Authorisation holderHospira UK Limited
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameCisplatin
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCISPLATIN
    D.3.9.3Other descriptive nameCISPLATIN
    D.3.9.4EV Substance CodeSUB07483MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 12
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Endoxan
    D.2.1.1.2Name of the Marketing Authorisation holderBaxter Oncology GmbH
    D.2.1.2Country which granted the Marketing AuthorisationHungary
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameCyclophosphamide
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCYCLOPHOSPHAMIDE
    D.3.9.1CAS number 50-18-0
    D.3.9.4EV Substance CodeSUB06859MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number500 to 1000
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Subjects with solid tumors of the type of colorectal cancer, pancreatic ductal adenocarcinoma, Squamous non-small cell lung cancer, non-squamous non-small cell lung cancer, any solid tumor that progressed on previous therapy with a PD-1 or PD-L1 inhibitor, urothelial carcinoma or squamous cell carcinoma of the head and neck
    Sujetos con tumors sólidos de tipo cancer colorectal, adenocarcinoma ductal pancreático, , carcinoma pulmonar no microcítico, cualquier tumor sólido que haya sufrido una progresión durante el tratamiento previo con un inhibidor de la proteína 1 de apoptosis o del ligando 1 de apoptosis o carcinoma epidermoide de cabeza y cuello
    E.1.1.1Medical condition in easily understood language
    subjects with solid tumors of the type of colorectal cancer, pancreatic cancer, non-small cell lung cancer, urothelial carcinoma or cell carcinoma of the head and neck
    Sujetos con tumors sólidos de tipo cancer colorectal, cancer pancreático, carcinoma pulmonar no microcítico, carcinoma urotelial o carcinoma epidermoide de cabeza y cuello
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10061451
    E.1.2Term Colorectal cancer
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10051971
    E.1.2Term Pancreatic adenocarcinoma
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10079440
    E.1.2Term Non-squamous non-small cell lung cancer
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10061873
    E.1.2Term Non-small cell lung cancer
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10064467
    E.1.2Term Urothelial carcinoma
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10060121
    E.1.2Term Squamous cell carcinoma of head and neck
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10065252
    E.1.2Term Solid tumor
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Phase 1: to evaluate the safety, tolerability, and dose-limiting toxicities (DLTs) and to define a maximum tolerated dose (MTD) and/or pharmacologically active dose (PAD) of epacadostat in combination with pembrolizumab and chemotherapy in subjects with advanced or metastatic solid tumors
    Phase 2: to evaluate the efficacy of epacadostat in combination with pembrolizumab and chemotherapy in subjects with advanced or metastatic CRC, PDAC, NSCLC, UC, SCCHN, or any advanced or metastatic solid tumor who progressed on previous therapy with a PD-1 or PD-L1 inhibitor by assessing objective response rate (OOR) per RECIST v1.1.
    Fase I: evaluar la seguridad, la tolerabilidad y las toxicidades limitantes de la dosis (TLD) y definir la dosis máxima tolerada (DMT) y/o la dosis farmacológicamente activa (DFA) de epacadostat en combinación con pembrolizumab y quimioterapia en pacientes con tumores sólidos avanzados o metastásicos.
    • Fase II: evaluar la eficacia de epacadostat en combinación con pembrolizumab y quimioterapia en pacientes con CCR, ADP, CPNM, CU o CECC avanzados o metastásicos o cualquier tumor sólido avanzado o metastásico que haya experimentado una progresión durante el tratamiento previo con un inhibidor de la PD-1 o del PD-L1 mediante la determinación de la tasa de respuesta objetiva (TRO) en función de los criterios RECIST v. 1.1.
    E.2.2Secondary objectives of the trial
    Phase 1: To explore the efficacy of epacadostat in combination with pembrolizumab and chemotherapy in subjects with advanced or metastatic solid tumors by assessing ORR per RECIST v1.1
    Phase 2: To further evaluate the safety and tolerability of epacadostat at the MTD and/or PAD in combination with pembrolizumab and chemotherapy in subjects with selected advance or metastatic solid tumors
    Phases 1 and 2:
    To evaluate the efficacy of epacadostat in combination with pembrolizumab and chemotherapy in subjects with advanced or metastatic solid tumors (Phase 1) and selected advanced or metastatic solid tumors (Phase 2) by assessing DOR and PFS per RECIST v1.1 and by assessing ORR, DOR, and PFS per immune-related RECIST
    To evaluate the PK of epacadostat in combination with pembrolizumab and chemotherapy in subjects with advanced or metastatic solid tumors (Phase 1) and selected advanced or metastatic solid tumors (Phase 2)
    • Fase I: estudiar la eficacia de epacadostat en combinación con pembrolizumab y quimioterapia en pacientes con tumores sólidos avanzados o metastásicos mediante la evaluación de la TRO en función de los criterios RECIST v. 1.1.
    • Fase II: evaluar de nuevo la seguridad y la tolerabilidad de epacadostat a la DMT y/o la DFA en combinación con pembrolizumab y quimioterapia en pacientes con tumores sólidos avanzados o metastásicos seleccionados.
    • Fases I y II: evaluar la eficacia de epacadostat en combinación con pembrolizumab y quimioterapia en pacientes con tumores sólidos avanzados o metastásicos (fase I) y tumores sólidos avanzados o metastásicos seleccionados (fase II) mediante la determinación de la duración de la respuesta (DR) y la supervivencia sin progresión (SSP) en función de los criterios RECIST v. 1.1.
    • Fases I y II: evaluar la eficacia de epacadostat en combinación con pembrolizumab y quimioterapia en pacientes con tumores... (ver resúmen del protocol en español)
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    • Men or women aged 18 years or older.
    • Presence of measurable disease per RECIST v1.1. Tumor lesions located in a previously irradiated area, or in an area subjected to other loco-regional therapy, are considered measureable if progression has been demonstrated in the lesion.
    • ECOG performance status of 0 or 1.
    • Willing to avoid pregnancy or fathering children from screening through 120 days after the last dose of epacadostat and pembrolizumab based on criteria defined in the body of the Protocol.
    Phase 1 subjects only:
    • Subjects with locally advanced or metastatic solid tumors who have disease progression after treatment with available therapies that are known to confer clinical benefit, or who are intolerant to treatment, or subjects who refuse standard treatment. Locally advanced disease must not be amenable to resection with curative intent.
    • Subjects must not have received therapy with an IDO inhibitor.
    Phase 2 CRC subjects only:
    • Histologically or cytologically confirmed advanced or metastatic adenocarcinoma of the colon or rectum.
    • Subjects must not have received previous chemotherapy as first-line therapy for advanced or metastatic disease.
    • Subjects must not have received previous immune checkpoint inhibitors (eg, cytotoxic T-lymphocyte–associated protein 4 [CTLA-4] inhibitor, PD-1 inhibitor, PD-L1 inhibitor, or any other antibody or drug specifically targeting T-cell costimulation), and/or an IDO inhibitor.
    Phase 2 PDAC subjects only:
    • Histologically or cytologically confirmed advanced or metastatic PDAC.
    • Subjects must not have received previous chemotherapy as first-line therapy for advanced or metastatic disease.
    • Subjects must not have received previous immune checkpoint inhibitors (eg, CTLA-4 inhibitor, PD-1 inhibitor, PD-L1 inhibitor, or any other antibody or drug specifically targeting T-cell costimulation), and/or an IDO inhibitor.
    Phase 2 squamous or nonsquamous NSCLC subjects only:
    • Histologically or cytologically confirmed Stage IIIB, Stage IV, or recurrent squamous or nonsquamous NSCLC.
    • Subjects without driver mutations (eg, BRAF or epidermal growth factor receptor [EGFR] mutations, anaplastic lymphoma kinase (ALK) fusion oncogene or ROS1 rearrangements) must not have received previous chemotherapy as first-line therapy for Stage IIIB, Stage IV, or recurrent NSCLC.
    • Subjects with driver mutations (eg, BRAF or EGFR mutations, ALK fusion oncogene or ROS1 rearrangements) must have received prior treatment only with an approved kinase inhibitor with subsequent disease progression.
    • Subjects must not have received previous immune checkpoint inhibitors (eg, CTLA-4 inhibitor, PD-1 inhibitor, PD-L1 inhibitor, or any other antibody or drug specifically targeting T-cell costimulation), and/or an IDO inhibitor.
    Phase 2 subjects in the cohort of subjects with any solid tumor that progressed on previous therapy with a PD-1 or PD-L1 inhibitor only:
    • Histologically or cytologically confirmed advanced or metastatic solid tumors that progressed on previous monotherapy with a PD-1 or PD-L1 inhibitor or previous combination therapy that included a PD-1 or PD-L1 inhibitor.
    • Subjects must not have received previous therapy with an IDO inhibitor.
    • Subjects may have received previous chemotherapy for advanced or metastatic disease.
    Phase 2 subjects in the mandatory biopsy cohort only:
    • Willing to undergo pretreatment and on-treatment core or excisional tumor biopsies.
    Phase 2 efficacy expansion subjects only:
    • Willing to undergo pretreatment core or excisional tumor biopsies.
    Phase 2 UC subjects only:
    • Have histologically or cytologically confirmed advanced/unresectable (inoperable) or metastatic urothelial cancer of the renal pelvis, ureter, bladder, or urethra. Both transitional cell and mixed transitional/non-transitional (predominantly transitional) cell histologies are allowed.
    • Subjects must not have received previous chemotherapy as first-line therapy for advanced or metastatic disease.
    • Subjects must not have received previous immune checkpoint inhibitors (eg, CTLA-4 inhibitor, PD-1 inhibitor, PD-L1 inhibitor, or any other antibody or drug specifically targeting T-cell costimulation), and/or an IDO inhibitor.
    Phase 2 SCCHN subjects only:
    • Histologically or cytologically-confirmed recurrent or metastatic SCCHN of the oral cavity, oropharynx, hypopharynx, and larynx that is considered incurable by local therapies.
    • Documentation of results from testing of human papilloma virus (HPV) status for oropharyngeal cancer using p16 IHC testing.
    • Subjects must not have received previous chemotherapy as first-line therapy for recurrent or metastatic disease.
    • Subjects must not have received previous immune checkpoint inhibitors (eg, CTLA-4 inhibitor, PD-1 inhibitor, PD-L1 inhibitor, or any other antibody or drug specifically targeting T-cell costimulation), and/or an IDO inhibitor.
    • Hombres o mujeres de 18 años de edad o más.
    • Presencia de un tumor mensurable en función de los criterios RECIST v1.1. Las lesiones tumorales situadas en un área previamente irradiada o en un área sometida a otro tratamiento locorregional se consideran si se ha demostrado la progresión en la lesión.
    • Estado funcional del ECOG de 0 o 1.
    • Estar dispuesto a evitar un embarazo o a no concebir un hijo desde la fase de selección hasta 120 días después de la última dosis de epacadostat y pembrolizumab basándose en los criterios definidos en el texto del protocolo.
    Solo pacientes de la fase I:
    • Pacientes con tumores sólidos localmente avanzados o metastásicos que presenten una progresión tras recibir los tratamientos disponibles que se sabe que producen un beneficio clínico, que no toleren el tratamiento o que rechacen el tratamiento de referencia. El tumor localmente avanzado no debe ser susceptible de una resección con fines curativos.
    Nota: los pacientes no deberán haber recibido más de dos tratamientos previos para el cáncer avanzado o metastásico. En el caso de pacientes que hayan recibido más de dos tratamientos previos para el cáncer avanzado o metastásico, deberá consultarse con el supervisor médico para confirmar su elegibilidad.
    • Los pacientes no deberán haber recibido un tratamiento previo con un inhibidor de la IDO.
    Solo pacientes de la fase II con CCR:
    • Adenocarcinoma del colon o del recto avanzado o metastásico confirmado mediante histología o citología.
    • Los pacientes no deberán haber recibido tratamiento previo con quimioterapia como tratamiento de primera línea para el cáncer avanzado o metastásico.
    Nota: serán elegibles los pacientes que hayan finalizado un tratamiento quimioterapéutico como adyuvante, neoadyuvante o en el marco de un tratamiento quimiorradioterapéutico y hayan registrado una progresión ≥6 meses después de finalizar dicho tratamiento. Si la progresión se produjo <6 meses después de terminar el tratamiento, el paciente no será elegible.
    • Los pacientes no deberán haber recibido previamente inhibidores de los puntos de control inmunitarios (p. ej., un inhibidor del antígeno 4 del linfocito T citotóxico [CTLA-4], un inhibidor de la PD-1, un inhibidor del PD-L1 o cualquier otro fármaco o anticuerpos específicamente dirigidos a la coestimulación de los linfocitos T) o un inhibidor de la IDO. En el caso de pacientes que hayan recibido otras inmunoterapias, deberá consultarse con el supervisor médico para confirmar su elegibilidad.
    Solo pacientes de la fase II con ADP:
    • ADP avanzado o metastásico confirmado mediante histología o citología.
    • Los pacientes no deberán haber recibido tratamiento previo con quimioterapia como tratamiento deprimera línea para el cáncer avanzado o metastásico.
    Nota: serán elegibles los pacientes que hayan finalizado un tratamiento quimioterapéutico como adyuvante, neoadyuvante o en el marco de un tratamiento quimiorradioterapéutico y hayan registrado una progresión ≥6 meses después de finalizar dicho tratamiento. Si la progresión se produjo <6 meses después de terminar el tratamiento, el paciente no será elegible.
    • Los pacientes no deberán haber recibido previamente inhibidores de los puntos de control inmunitarios (p. ej., un inhibidor del CTLA-4, un inhibidor de la PD-1, un inhibidor del PD-L1 o cualquier otro fármaco o anticuerpos específicamente dirigidos a la coestimulación de linfocitos T) o un inhibidor de la IDO. En el caso de pacientes que hayan recibido otras inmunoterapias, deberá consultarse con el supervisor médico para confirmar su elegibilidad.
    Solo pacientes de la fase II con CPNM epidermoide o no epidermoide:
    • CPNM epidermoide o no epidermoide en estadio IIIB, IV o recidivante confirmado mediante histología o citología.
    • Pacientes con mutaciones oncoiniciadoras (p. ej., mutaciones del BRAF o del receptor del factor de crecimiento epidérmico [EGFR], o reordenamientos del oncogén de fusión de la cinasa del linfoma anaplásico [CLA] o del ROS1) que no hayan recibido quimioterapia como un tratamiento de primera línea para un CPNM de estadio IIIB, IV o recidivante.
    Nota: serán elegibles los pacientes que hayan finalizado un tratamiento quimioterapéutico como adyuvante, neoadyuvante o en el marco de un tratamiento quimiorradioterapéutico y hayan registrado una progresión ≥6 meses después de finalizar dicho tratamiento. Si la progresión se produjo <6 meses después de terminar el tratamiento, el paciente no será elegible.
    • Los pacientes con mutaciones oncoiniciadoras (p. ej., mutaciones de BRAF o del EGFR, o reordenamientos del oncogén de fusión de la CLA o del ROS1) que han recibido un tratamiento previo solo con un inhibidor autorizado de la cinasa con la subsiguiente progresión de la enfermedad.
    • Los pacientes no deberán haber recibido previamente inhibidores de los puntos de control inmunitarios (p. ej., un inhibidor del CTLA-4, un inhibidor de la PD-1, un inhibidor del... (ver resúmen del protocol en español)
    E.4Principal exclusion criteria
    • Laboratory and medical history parameters not within the Protocol-defined range. If the screening laboratory tests below were conducted > 7 days before treatment initiation, they will need to be repeated on Cycle 1 Day 1 before initiation of treatment.
    - Absolute neutrophil count < 1.5 × 109/L.
    - Platelet count < 100 × 109/L.
    - Hemoglobin < 9 g/dL or < 5.6 mmol/L.
    - Serum creatinine > 1.5 × institutional upper limit of normal (ULN), OR measured or calculated creatinine clearance (glomerular filtration rate can also be used in place of creatinine or creatinine clearance) < 50 mL/min for subjects with creatinine levels > 1.5 × institutional ULN.
    - Aspartate aminotransferase, alanine aminotransferase (ALT), and alkaline phosphatase ≥ 2.5 × ULN.
    - Total bilirubin ≥ 1.2 × ULN.
    - International normalized ratio (INR), prothrombin time, and activated partial thromboplastin time (aPTT) > 1.5 × ULN (unless the subject is receiving anticoagulant therapy, in which case the subject may be included as long as the INR, prothrombin time, and aPTT are within therapeutic range of intended use of anticoagulants).
    • Receipt of anticancer medications or investigational drugs within the following intervals before Cycle 1 Day 1:
    - ≤ 14 days for chemotherapy or targeted small molecule therapy.
    - ≤ 28 days for previous monoclonal antibody used for anticancer therapy.
    - ≤ 7 days for immune-suppressive–based treatment for any reason.
    - ≤ 28 days or 5 half-lives (whichever is longer) before Cycle 1 Day 1 for all other investigational agents or devices. For investigational agents with long half-lives (eg, > 5 days), enrollment before the fifth half-life requires medical monitor approval.
    • Previous radiotherapy within 14 days of Cycle 1 Day 1 (except for radiation to the central nervous system [CNS], which requires a ≥ 28-day washout as described below). Subjects must also not require chronic use of corticosteroids and must not have had radiation pneumonitis as a result of treatment.
    • Known active CNS metastases and/or carcinomatous meningitis.
    • Has not recovered to ≤ Grade 1 from toxic effects of previous therapy and/or complications from previous surgical intervention before starting study therapy.
    • Receipt of a live vaccine within 30 days of planned start of study therapy.
    • Active infection requiring systemic therapy.
    • Subjects who have any active or inactive autoimmune disease or syndrome (ie, rheumatoid arthritis, moderate or severe psoriasis, multiple sclerosis, inflammatory bowel disease) that has required systemic treatment in the past 2 years or who are receiving systemic therapy for an autoimmune or inflammatory disease (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs).
    • History of (noninfectious) pneumonitis that required steroids or current pneumonitis or interstitial lung disease.
    • History of organ transplant that requires use of immunosuppressive therapy, has a diagnosis of immunodeficiency, or is receiving chronic systemic steroid therapy (in doses exceeding 10 mg daily of prednisone or its equivalent) or any other form of immunosuppressive therapy within 7 days before Cycle 1 Day 1.
    Known history of or screening test is positive for hepatitis B virus (HBV; eg, HBsAg reactive or HBV DNA detected) or hepatitis C virus (HCV; HCV antibody positive and/or HCV RNA qualitative is detected).
    • Known history of human immunodeficiency virus (HIV; HIV 1/2 antibodies).
    • History or presence of an ECG that, in the investigator's opinion, is clinically meaningful.
    • Clinically significant cardiac disease, including unstable angina, acute myocardial infarction within 6 months of Cycle 1 Day 1, New York Heart Association Class III or IV congestive heart failure, and arrhythmia requiring therapy.
    • Subjects with a history of bleeding related to cancer under study requiring a medical intervention (eg, embolization procedure, RBC transfusion, or hospitalization) within 30 days of study enrollment.
    • Known allergy or severe hypersensitivity (≥ Grade 3) reaction to any component of epacadostat, pembrolizumab, or chemotherapy regimen components and/or their formulation excipients.
    • Presence of a gastrointestinal condition (eg, inflammatory bowel disease, Crohn's disease, ulcerative colitis) that may affect drug absorption.
    • Receiving monoamine oxidase inhibitors (MAOIs) or drug that has significant MAOI activity (eg, meperidine, linezolid, methylene blue) within the 21 days before screening.
    • Women who are pregnant or breastfeeding.
    Phase 2 CRC subjects only:
    • Known dihydropyrimidine dehydrogenase deficiency (heterozygous or homozygous mutations).
    Phase 2 subjects in the cohort of subjects with any solid tumor that progressed on previous therapy with a PD-1 or PD-L1 inhibitor only:
    • History of any grade immune-related ocular AEs.
    • History of a ≥ Grade 3 immune-related AE from previous immunotherapies.
    • Current urinary outflow obstruction.
    • Parámetros analíticos o en los antecedentes médicos fuera del intervalo definido en el protocolo. Si los siguientes análisis clínicos de selección se realizaron >7 días antes del inicio del tratamiento, deberán repetirse el día 1 del ciclo 1, antes del inicio del tratamiento.
    - Cifra absoluta de neutrófilos <1,5 × 109/l.
    - Cifra de trombocitos <100 × 109/l.
    - Hemoglobina <9 g/dl o <5,6 mmol/l.
    - Creatinina sérica >1,5 veces el límite superior de la normalidad (LSN) del centro O BIEN aclaramiento de creatinina (ACr) determinado o calculado (la tasa de filtración glomerular también podrá usarse en lugar de la creatinina o el ACr) <50 ml/min en pacientes con niveles de creatinina >1,5 veces el LSN del centro.
    - Aspartato-aminotransferasa, alanina-aminotransferasa (ALT) y fosfatasa alcalina (FA) ≥2,5 veces el LSN.
    Nota: los pacientes 1) con metástasis óseas y 2) sin metástasis hepáticas parenquimatosas en las pruebas radiográficas de la selección podrán incluirse si la fosfatasa alcalina es ≤5 veces el LSN. Los pacientes con 1) metástasis óseas y 2) metástasis hepáticas parenquimatosas en las pruebas radiográficas de la selección podrán incluirse si la fosfatasa alcalina es ≤5 veces el LSN solo con la autorización del supervisor médico.
    - Bilirrubina total ≥1,2 veces el LSN.
    Nota: si la bilirrubina total es ≥1,2 veces el LSN, deberá analizarse la bilirrubina conjugada (directa), y los pacientes quedarán excluidos si el valor es ≥2,0 veces el LSN o ≥40 % de la bilirrubina total si no se dispone de LSN en el centro.
    - Índice internacional normalizado (IIN), tiempo de protrombina (TP) o tiempo de tromboplastina parcial activado (TTPa) >1,5 veces el LSN (a menos que el paciente esté recibiendo un tratamiento anticoagulante, en cuyo caso el paciente podrá ser incluido siempre que el IIN o el TTPa estén dentro del intervalo terapéutico del uso previsto de los anticoagulantes).
    Nota: el tiempo de tromboplastina parcial podrá utilizarse en lugar del TTPa si así lo prevén las directrices del centro.
    • Recepción de medicamentos antineoplásicos o experimentales en los siguientes intervalos antes del día 1 del ciclo 1:
    - ≤14 días para la quimioterapia o los tratamientos con moléculas bien caracterizadas.
    Nota: se permitirá la administración concomitante de bisfosfonatos.
    - ≤28 días para el uso previo de anticuerpos monoclonales para el tratamiento antineoplásico.
    Nota: se permite el uso de denosumab.
    - ≤7 días en el caso de tratamientos basados en inmunodepresores por cualquier motivo.
    Nota: se permite el uso de esteroides tópicos o inhalados, la profilaxis con corticoides para procedimientos radiográficos o corticoesteroides sistémicos en dosis de ≤10 mg/día de prednisona o su equivalente.
    - ≤28 días o 5 semividas (lo que sea más largo) antes del día 1 del ciclo 1 para todos los fármacos o dispositivos experimentales. En el caso de fármacos experimentales con una semivida larga (p. ej., >5 días), la inclusión antes de la quinta semivida precisará de la autorización del supervisor médico.
    • Radioterapia previa en un plazo de 14 días del día 1 del ciclo 1 (excepto en caso de radioterapia que afecte al sistema nervioso central [SNC], que precisará de un periodo de reposo farmacológico ≥28 días, tal y como se describe a continuación). Los pacientes no deberán requerir el uso corticoesteroides y no deberán haber sufrido neumonía por radiación como consecuencia del tratamiento. Se permitirá una semana de reposo farmacológico para la radiación paliativa de un tumor que no afecte al SNC siempre que así lo autorice el promotor.
    • Metástasis en el sistema nervioso central activas conocidas o meningitis carcinomatosa.
    Nota: los pacientes tratados previamente por metástasis cerebrales podrán participar siempre que estén estables (sin indicios de progresión en las pruebas de diagnóstico por imagen durante ≥28 días antes del día 1 del ciclo 1 y siempre que cualquier síntoma neurológico haya remitido hasta su valor basal), no presenten ningún indicio de metástasis cerebrales nuevas o en progresión ni edema cerebral, y no hayan requerido el uso de corticoesteroides durante ≥14 días antes del día 1 del ciclo 1. Esta excepción no incluye los casos de meningitis carcinomatosa, que se excluirán independientemente de su estabilidad clínica.
    Nota: los pacientes con indicios de edema cerebral o en los casos en que hayan transcurrido <28 días desde la radioterapia que afecte al SNC quedarán excluidos del estudio.
    • Efectos tóxicos de un tratamiento previo y/o complicaciones de una intervención quirúrgica previa que no remitan a un grado ≤1 antes del inicio del tratamiento.
    Nota: los pacientes con AA crónicos estables (grado ≤2) que no se espera que se resuelvan (p. ej., alopecia) se considerarán excepciones y podrán ser incluidos.
    Nota: los pacientes con antecedentes de neuropatía periférica de grado ≥2 quedarán excluidos.
    • Haber recibido una vacuna con microbios vivos en un... (ver resúmen del protocol en español)
    E.5 End points
    E.5.1Primary end point(s)
    • Phase 1: Safety and tolerability will be assessed by monitoring frequency, duration, and severity of adverse events (AEs) through physical examinations, by evaluating changes in vital signs and electrocardiograms (ECGs), and through clinical laboratory blood and urine sample evaluations.
    • Phase 2: ORR, defined as the percentage of subjects having a complete response (CR) or partial response (PR), will be determined by investigator assessment of radiographic disease per RECIST v1.1.
    • Fase I: la seguridad y la tolerabilidad, que se evaluarán mediante el seguimiento de la frecuencia, la duración y la intensidad de los acontecimientos adversos (AA) mediante exploraciones físicas y la evaluación de los cambios en las constantes vitales y los electrocardiogramas (ECG), y pruebas analíticas en sangre y orina.
    • Fase II: la TRO, definida como el porcentaje de pacientes que muestren una respuesta completa (RC) o una respuesta parcial (RP), se determinará mediante la valoración por parte del investigador de las evaluaciones radiográficas de la enfermedad en función de los criterios RECIST v. 1.1.
    E.5.1.1Timepoint(s) of evaluation of this end point
    every study visit
    cada visita del estudio
    E.5.2Secondary end point(s)
    • Phase 1: ORR, defined as the percentage of subjects having a CR or PR, will be determined by investigator assessment of radiographic disease per RECIST v1.1.
    • Phase 2: Safety and tolerability will be assessed by monitoring frequency, duration, and severity of AEs through physical examinations, by evaluating changes in vital signs and ECGs, and through clinical laboratory blood and urine sample evaluations.
    • Phases 1 and 2: DOR is defined as the time from earliest date of CR or PR (as determined by investigator assessment of radiographic disease assessment per RECIST v1.1) until the earliest date of disease progression or death due to any cause, if occurring sooner than disease progression.
    • Phases 1 and 2: PFS is defined as the time from date of first dose of study medication until the earliest date of disease progression (as determined by investigator assessment of radiographic disease assessment per RECIST v1.1), or death due to any cause, if occurring sooner than progression.
    • Phase 1 and Phase 2: ORR, DOR, and PFS are as defined above but will be evaluated using irRECIST.
    • Phases 1 and 2: PK of epacadostat will be assessed by summarizing Cmin, Cmax, tmax, AUC0-t, and AUC0-τ.
    • Fase I: la TRO, definida como el porcentaje de pacientes que muestren una RC o una RP, se determinará mediante la valoración por parte del investigador de las evaluaciones radiográficas de la enfermedad en función de los criterios RECIST v. 1.1.
    • Fase II: la seguridad y la tolerabilidad se evaluarán mediante el seguimiento de la frecuencia, la duración y la intensidad de los AA mediante exploraciones físicas, la evaluación de los cambios en las constantes vitales y los ECG, y pruebas analíticas en sangre y orina.
    • Fases I y II: la DR se define como el tiempo desde la primera fecha de RC o RP (según la valoración del investigador de las evaluaciones radiográficas de la enfermedad en función de los criterios RECIST v. 1.1) hasta la primera fecha de progresión de la enfermedad o la muerte por cualquier causa, si esta se produce antes que la progresión de la enfermedad.
    • Fases I y II: la SSP, definida como el tiempo transcurrido desde la fecha de administración de la primera dosis del fármaco en estudio hasta la primera fecha de progresión tumoral (según la valoración del investigador de las evaluaciones radiográficas de la enfermedad en función de los criterios RECIST v. 1.1) o la muerte por cualquier causa, si esta se produce antes que la progresión.
    • Fases I y II: se evaluarán la TRO, la DR y la SSP tal y como se definen con anterioridad, pero usando los criterios irRECIST.
    • Fases I y II: la FC de epacadostat se evaluará resumiendo Cmín, Cmáx, tmáx, ABC0-t y ABC0-τ.
    E.5.2.1Timepoint(s) of evaluation of this end point
    every study visit
    cada visita del estudio
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E.7.1.3.1Other trial type description
    Phase 1/2 - evaluation of safety and tolerability: of combination therapy
    Fase I/II- evaluación de la seguridad y tolerabilidad: eficacia prelimilar MDT de terapia combinada
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial7
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA4
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Italy
    Spain
    United States
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The end of the study will occur when all subjects have discontinued epacadostat and pembrolizumab and have completed applicable safety follow-up assessments.. If there are ≤ 5 subjects on study for more than 6 months, a database lock of the study may occur to allow the analysis of the study data. Any remaining subjects may continue to receive study treatment per protocol.
    El final del studio ocurrirá cuando todos los pacientes hayan suspendido epacadostat y pembrolizumab y hayan completado las evaluaciones de seguimiento de seguridad aplicables. Si existen ≤ 5 sujetos en el studio durante mas de 6 meses, podría realizarse un corte en la base de datos del studio para permitir el análisis de los datos del estudio. Cualquier sujeto que quede puede continuar recibiendo el tratamiento del estudio según el protocolo
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years5
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years5
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 300
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 121
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state20
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 210
    F.4.2.2In the whole clinical trial 421
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Any remaining subjects may continue to receive study treatment and be seen by the investigator per usual standard of care for this population.
    Cualquier sujeto que quede puede continuar recibiendo el tratamiento del estudio y ser visto por el investigador de acuerdo al cuidado estandar para esta población
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2018-05-31
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-05-29
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2018-10-25
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