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    The EU Clinical Trials Register currently displays   43851   clinical trials with a EudraCT protocol, of which   7283   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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    Summary
    EudraCT Number:2015-001852-32
    Sponsor's Protocol Code Number:3475-164
    National Competent Authority:Germany - PEI
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2015-08-13
    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 ConcernedGermany - PEI
    A.2EudraCT number2015-001852-32
    A.3Full title of the trial
    A Phase II Study of Pembrolizumab (MK-3475) as Monotherapy in Subjects with Previously Treated Locally Advanced Unresectable or Metastatic (Stage IV) Mismatched Repair Deficient or Microsatellite Instability-High Colorectal Carcinoma (KEYNOTE-164)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase II Study of Pembrolizumab in Previously Treated Subjects with Mismatched Repair Deficient or Microsatellite Instability-High Colorectal Carcinoma
    A.3.2Name or abbreviated title of the trial where available
    Phase II Study of Pembrolizumab in Subjects with MMRd or MSI-H CRC
    A.4.1Sponsor's protocol code number3475-164
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT02460198
    A.5.4Other Identifiers
    Name:KEYNOTENumber:164
    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 SponsorMerck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
    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 supportMerck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMerck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
    B.5.2Functional name of contact pointGlobal Clinical Trials Operations
    B.5.3 Address:
    B.5.3.1Street AddressOne Merck Drive, P.O. Box 100
    B.5.3.2Town/ cityWhite House Station, NJ
    B.5.3.3Post code08889-0100
    B.5.3.4CountryUnited States
    B.5.4Telephone number+1732594 7569
    B.5.5Fax number+1732594 6601
    B.5.6E-mails.peter.kang@merck.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 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.3.9.3Other descriptive nameAnti-PD-1 monoclonal antibody
    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) Yes
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    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
    Colorectal Carcinoma
    E.1.1.1Medical condition in easily understood language
    colorectal cancer
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Objective (Cohort A): To evaluate the Objective Response Rate (ORR) per RECIST 1.1 assessed by central imaging vendor of the 200 mg Q3W
    dose of pembrolizumab in subjects with locally advanced unresectable or
    metastatic MMR deficient or MSI high CRC and who have been previously treated with standard of care therapies, which must include
    fluoropyrimidine, oxaliplatin, and irinotecan.

    Objective (Cohort B): To estimate the ORR per RECIST 1.1 assessed by
    central imaging vendor, of the 200 mg Q3W dose of pembrolizumab in
    subjects with locally advanced unresectable or metastatic MMR deficient or MSI high CRC and who have been previously treated with at least one line of systemic standard of care therapy (fluoropyrimidine + oxaliplatin or fluoropyrimidine + irinotecan +/- anti-VEGF/EGFR monoclonal antibody).
    E.2.2Secondary objectives of the trial
    The secondary efficacy objectives of this study are to evaluate the ORR
    and DOR, DCR, PFS per RECIST 1.1 as assessed by the central imaging
    vendor, and OS in both Cohort A and Cohort B separately.
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Merck will conduct Future Biomedical Research on DNA (blood and tissue) specimens collected during this clinical trial. Such research is for biomarker testing to address emergent questions and will only be conducted on specimens from appropriately consented subjects. The objective of collecting specimens for Future Biomedical Research is to explore and identify biomarkers that inform the scientific understanding of diseases and/or their therapeutic treatments. The overarching goal is to use such information to develop safer, more effective drugs, and/or to ensure that subjects receive the correct dose of the correct drug at the
    correct time. Additional biomarker research to identify factors important
    for MK-3475 therapy will be pursued in Cohort B and are optional in
    Cohort A.
    On cohort B there will be a plasma Sample for Circulating Tumor DNA
    Study; A plasma sample will be collected prior to treatment at the Cycle 1, Cycle 3, and discontinuation visits for planned analysis of circulating tumor DNA.
    E.3Principal inclusion criteria
    Subjects must: be male or female subjects who are ≥ 18 years of age on
    the day of signing the informed consent. Locally confirmed MMR
    deficient or MSI-h CRC. Have a histologically proven locally advanced
    unresectable or metastatic (Stage IV) CRC. Have been previously treated with standard therapies, which must include, for Cohort A, fluoropyrimidine, oxaliplatin and irinotecan and for Cohort B, at least 1 line of systemic standard of care therapy (fluoropyrimidine + oxaliplatin or fluoropyrimidine + irinotecan +/- anti-VEGF/EGFR monoclonal antibody). Subjects who have withdrawn from therapy standard treatment due to unacceptable toxicity warranting discontinuation of that treatment and precluding retreatment with the same agent before progression of disease will also be eligible. Regimens given with adjuvant intent will be counted as treatment for metastatic disease if the patient's disease had progressed within 6 month following treatment. Have an ECOG performance status of 0 or 1. Have a life expectancy of greater than 3 months. Have at least one measureable lesion by RECIST 1.1 as determined by central review for response assessment. Provide an archival or newly obtained tumor tissue sample (Cohort B). Subjects failing screening criteria in Cohort A may be rescreened for Cohort B only after consultation with the SPONSOR.
    E.4Principal exclusion criteria
    Subjects will be excluded if he/she: is currently participating in another
    study and receiving trial treatment, has participated in a study of an
    investigational agent and received trial treatment within 4 weeks of the
    first dose of treatment in this study, or used an investigational device
    within 4 weeks of the first dose of treatment in this study. Has an active
    autoimmune disease that has required systemic treatment in past 2
    years (i.e. with use of disease modifying agents, corticosteroids or
    immunosuppressive drugs). Replacement therapy (eg. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to
    the first dose of trial treatment.
    Has known active central nervous system (CNS) metastases and/or
    carcinomatous meningitis. Subjects with previously treated brain
    metastases may participate provided they have stable brain metastases
    [without evidence of progression by imaging [confirmed by magnetic
    resonance imaging (MRI) if MRI was used at prior imaging, or confirmed
    by computed tomography (CT) imaging if CT used at prior imaging] for at least four weeks prior to the first dose of trial treatment; also, any
    neurologic symptoms must have returned to baseline], have no evidence of new or enlarging brain metastases, and have not used steroids for brain metastases for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis, as subjects with carcinomatous meningitis are excluded regardless of clinical stability. Has had prior monoclonal antibody (mAb), chemotherapy, targeted small
    molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. Has received a live vaccine within 30 days of planned start of study therapy. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected). Has known history of, or any evidence of interstitial lung disease or active, non-infectious pneumonitis. Has an active infection requiring systemic therapy.
    E.5 End points
    E.5.1Primary end point(s)
    ORR based on RECIST 1.1 assessed by central imaging vendor
    E.5.1.1Timepoint(s) of evaluation of this end point
    There is one interim analysis planned in this study for Cohort A and no Interims Analysis planned for Cohort B.
    E.5.2Secondary end point(s)
    Objective response rate (ORR) - irRECIST assessed by central imaging vendor
    Disease Control Rate (DCR) - RECIST 1.1 and irRECIST assessed by central imaging vendor
    Duration of Response (DOR) - RECIST 1.1 and irRECIST assessed by central imaging vendor
    Progression-free Survival (PFS) - RECIST 1.1 and irRECIST assessed by central imaging vendor
    Overall survival (OS)
    E.5.2.1Timepoint(s) of evaluation of this end point
    Response assessments for endpoints are being evaluated throughout the study; imaging assessment to support the endpoints are obtained every 9 weeks for the first 12 months, then every 12 weeks thereafter, or more frequently if clinically indicated.
    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 Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    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 trial1
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA12
    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
    Australia
    Belgium
    Canada
    France
    Germany
    Israel
    Japan
    Korea, Republic of
    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 overall trial ends when fewer than 25% of subjects are evaluable for OS or all subjects have discontinued trial treatment (including retreatment), whichever occurs earlier.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months24
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial months24
    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: 110
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 10
    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 state3
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 24
    F.4.2.2In the whole clinical trial 120
    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)
    Once the participant has achieved the study objective or the study has ended, the participant is discontinued from this study and may be enrolled in an extension study to continue protocol-defined assessments and treatment.
    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 Decision2015-10-20
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-12-11
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2021-02-19
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
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