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    The EU Clinical Trials Register currently displays   40640   clinical trials with a EudraCT protocol, of which   6630   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2015-002067-41
    Sponsor's Protocol Code Number:3475-158
    National Competent Authority:France - ANSM
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2016-02-23
    Trial 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 ConcernedFrance - ANSM
    A.2EudraCT number2015-002067-41
    A.3Full title of the trial
    A Clinical Trial of Pembrolizumab (MK-3475) Evaluating Predictive Biomarkers in Subjects with Advanced Solid Tumors (KEYNOTE 158)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    PhII Trial of Pembrolizumab in Advanced Solid Tumors
    A.3.2Name or abbreviated title of the trial where available
    KEYNOTE-158
    A.4.1Sponsor's protocol code number3475-158
    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/ cityWhitehouse Station, NJ
    B.5.3.3Post code08889-0100
    B.5.3.4CountryUnited States
    B.5.4Telephone number+1732594 7653
    B.5.5Fax number+1732594 5512
    B.5.6E-mailscott.pruitt@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 1374853-91-4
    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.3.10 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
    A-Anal Squamous Cell Carcinoma (CA)
    B-Biliary Adenocarcinoma (Gallbladder&Biliary Tree but excluding Ampulla of Vater Cancers)
    C-Neuroendocrine Tumors (well&moderately-differentiated,including Carcinoid)
    D-Endometrial CA
    E-Cervical Squamous Cell CA
    F-Vulvar Squamous Cell CA
    G-Small Cell Lung CA
    H-Malignant Pleural Mesothelioma
    I-Thyroid CA (Papillary or Follicular Subtype)
    J-Salivary Gland CA OR
    K-Other advanced solid tumor (except CRC) which is MSI-H from a newly obtained tumor biopsy
    E.1.1.1Medical condition in easily understood language
    Advanced Solid Tumors
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.1
    E.1.2Level LLT
    E.1.2Classification code 10065143
    E.1.2Term Malignant solid tumour
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Objective 1: To evaluate the ORR to pembrolizumab, based on RECIST 1.1 as assessed by independent central radiologic review, in biomarker-unselected subjects with any one of multiple types of advanced (metastatic and/or unresectable) solid tumors (Groups A-J) for which prior standard of care (SOC) treatments have failed
    Objective 2: To evaluate the ORR to pembrolizumab, based on RECIST 1.1 as assessed by independent central radiologic review, in biomarker-selected subjects with any one of multiple types of advanced (metastatic and/or unresectable) solid tumors (Groups A-K) for which prior SOC treatments have failed. The primary biomarkers to be evaluated are (1) tumor expression of PD-L1 by IHC (Groups A-J), (2) tumor GEP by RNA analysis (Groups A-J), and (3) tumor MSI by DNA analysis (Groups A-J) or routine local testing (Group K).
    E.2.2Secondary objectives of the trial
    The following secondary objectives will be evaluated across the ten specified tumor types (Groups A-J):
    -To evaluate DOR (based on RECIST 1.1 as assessed by independent central radiologic review) in subjects receiving pembrolizumab and the relationship between DOR and tumor PD-L1 expression and GEP score
    -To evaluate PFS (based on RECIST 1.1 as assessed by independent central radiologic review ) in subjects receiving pembrolizumab and the relationship between PFS and tumor PD-L1 expression and GEP score
    - To evaluate OS in subjects receiving pembrolizumab and the relationship between OS and tumor PD-L1 expression and GEP score
    The following secondary objectives will be evaluated across all tumor types (Groups A-K):
    -To determine the safety and tolerability of pembrolizumab
    Refer to protocol for complete list
    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) specimens collected during this clinical trial. Such research is for biomarker testing to address emergent questions not described elsewhere in the protocol (as part of the main trial) 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.
    E.3Principal inclusion criteria
    1.Have a histologically or cytologically-documented, advanced (metastatic and/or unresectable) solid tumor that is incurable and for which prior standard first-line or later-line SOC treatments have failed. There is no limit to the number of prior treatment regimens.
    2.Have one of the following advanced (unresectable and/or metastatic) tumor types:
    (A)Anal Squamous Cell Carcinoma,
    (B)Biliary Adenocarcinoma (Gallbladder and Biliary Tree but excluding Ampulla of Vater Cancers),
    (C)Neuroendocrine Tumors (well- and moderately-differentiated, including Carcinoid),
    (D)Endometrial Carcinoma (a)
    (E)Cervical Squamous Cell Carcinoma,
    (F)Vulvar Squamous Cell Carcinoma,
    (G)Small Cell Lung Carcinoma,
    (H)Mesothelioma (Malignant Pleural Mesothelioma),
    (I)Thyroid Carcinoma (Papillary or Follicular Subtype),
    (J)Salivary Gland Carcinoma (a)
    OR
    (K)Any other advanced solid tumor (except CRC), which is MSI-H from a newly obtained tumor biopsy.

    (a)Note: All carcinoma subtypes are allowed; however, sarcomas or mesenchymal tumors are excluded.

    3.Have submitted an evaluable tissue sample for biomarker analysis from a newly obtained core, incisional, or excisional biopsy of a tumor lesion not previously irradiated (exceptions may be considered after Sponsor consultation). Note: A “newly obtained” tumor specimen (i.e., collected since the completion of the most recent cancer therapy) for biomarker characterization will be required for enrollment of all subjects. Tissue from tumor progressing at a site of prior radiation may be allowed for biomarker characterization, based on the Sponsor’s approval.
    4.If enrollment in Groups A-J has moved to biomarker enrichment, have a tumor that is positive for one or more of the pre-specified primary biomarker(s), as assessed by the central laboratory. These enrichment biomarkers may be PD-L1 expression by IHC (at a percentage to be prespecified), a positive tumor RNA GEP score (at a prespecified cut-off), and/or tumor MSI-H.
    5.Have radiologically measurable disease based on RECIST 1.1. Independent central radiologic review must confirm the presence of radiologically measureable disease based on RECIST 1.1 for the subject to be eligible to participate in the trial (see Site Procedure Manual for detailed instructions). Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.

    Refer to protocol for complete list
    E.4Principal exclusion criteria
    -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. The use of physiologic doses of corticosteroids may be approved after consultation with the Sponsor.
    -Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
    -Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from AEs due to mAbs administered more than 4 weeks earlier.
    -Has had prior 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.
    Refer to protocol for complete list.
    E.5 End points
    E.5.1Primary end point(s)
    ORR based on RECIST 1.1 as assessed by independent central radiologic review
    E.5.1.1Timepoint(s) of evaluation of this end point
    The trial incorporates an adaptive design in which multiple interim analyses may be performed. Results will be reviewed by the study team. The cutoffs for the three primary biomarker assays will be selected and specified before the first interim analysis. Details regarding the timing and conduct of the initial interim analysis will be further clarified in the sSAP. The planned sample size may be modified based on the interim results. The timing of additional interim analyses, the final analysis as well as the analysis plan will be documented in the sSAP. The sSAP will also be updated as the trial evolves.
    The primary endpoint of ORR will be used for all interim analyses with or without a confirmatory assessment; however, a confirmatory assessment is required for the final analysis
    E.5.2Secondary end point(s)
    Safety and Tolerability
    Duration of response (DOR)
    Progression-free survival (PFS)
    Overall survival (OS)
    (PK) for the 200 mg iv Q3W fixed dosing regimen
    E.5.2.1Timepoint(s) of evaluation of this end point
    Secondary efficacy endpoints will be summarized at the time that the primary analysis is conducted; however, these secondary endpoints are not likely to be mature at that time.
    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) 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 No
    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.8.3 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 concerned5
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA22
    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
    Denmark
    France
    Germany
    Italy
    Netherlands
    Norway
    Spain
    United Kingdom
    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
    LVLS
    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 months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years5
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    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: 260
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 260
    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 state35
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 130
    F.4.2.2In the whole clinical trial 520
    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)
    At the end of treatment, each subject will be followed for 30 days to monitor for AEs and events of clinical interest; subjects will be monitored for serious AEs for 90 days after the end of treatment. Subjects who discontinue for reasons other than PD will have follow-up for disease status until experiencing PD, initiating a non-study cancer treatment, withdrawing consent, or becoming lost to follow-up. All subjects will be followed by telephone for overall survival.
    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 Decision2016-01-22
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-12-10
    P. End of Trial
    P.End of Trial StatusOngoing
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
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