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    The EU Clinical Trials Register currently displays   44334   clinical trials with a EudraCT protocol, of which   7366   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:2012-003030-17
    Sponsor's Protocol Code Number:MK3475-002
    National Competent Authority:Sweden - MPA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2012-10-25
    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 ConcernedSweden - MPA
    A.2EudraCT number2012-003030-17
    A.3Full title of the trial
    Randomized, Phase II Study of Pembrolizumab (MK-3475) versus Chemotherapy in Patients with Advanced Melanoma (KEYNOTE 002)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Randomized, Phase II Study of MK-3475 compared to Chemotherapy in Patients with Advanced Melanoma
    A.4.1Sponsor's protocol code numberMK3475-002
    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 organisation
    B.5.2Functional name of contact point
    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 Powder for injection
    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 codeSCH 900475; MK-3475
    D.3.9.3Other descriptive nameAnti-PD-1 monoclonal antibody
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    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 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
    advanced melanoma (MEL) refractory to ipilimumab
    E.1.1.1Medical condition in easily understood language
    Skin cancer that has spread to other parts of the body
    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 10027480
    E.1.2Term Metastatic malignant melanoma
    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
    1) To evaluate the PFS in patients with IPI-refractory advanced MEL receiving either pembrolizumab or chemotherapy.
    2) To evaluate the OS in patients with IPI-refractory advanced MEL receiving either pembrolizumab or chemotherapy.
    E.2.2Secondary objectives of the trial
    1) To evaluate the ORR in patients with IPI-refractory advanced MEL receiving either pembrolizumab or chemotherapy.
    2) To evaluate the response duration in patients with IPI-refractory advanced MEL receiving either pembrolizumab or chemotherapy.
    3) To evaluate OS, PFS, and ORR in the biomarker positive subgroup defined by PD-L1 expression level (cutoff point to be estimated from external data) receiving either pembrolizumab or chemotherapy.
    4) To further characterize the PK profile of single agent pembrolizumab at 2 mg/kg and 10 mg/kg.
    5) To evaluate safety, tolerability and adverse experience profile of single agent pembrolizumab 2 mg/kg and 10 mg/kg.
    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 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) Patient must have a histologically or cytologically confirmed diagnosis of unresectable stage III or metastatic MEL not amenable to local therapy.
    2) Patients must be refractory to IPI.
    3) Resolution/improvement of IPI-related AEs (including irAEs) back to Grade 0-1 and ≤10 mg/day prednisone (or equivalent dose) for irAEs for at least 2 weeks prior to the first dose of study drug.
    4) Patients must consent to provide a newly obtained tumor tissue/biopsy (or specimen obtained within 60 days prior to consenting) for biomarker analysis from a core or excisional biopsy of a tumor lesion not previously irradiated.
    5) BRAF V600E or V600K mutation status must be known at Screening. Patients with BRAF mutant melanoma must have had a prior treatment regimen that included vemurafenib, dabrafenib, or an approved BRAF and/or MEK inhibitor.
    6) Patient must have at least 1 radiologically measurable lesion as per RECIST 1.1 (Appendix 6.1) defined as a lesion that is 10 mm in longest diameter or a lymph node that is 15 mm in short axis imaged by CT scan or MRI.
    7) Patient is ≥18 years of age on day of signing informed consent.
    8) Patient must have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale (Appendix 6.4).
    9) Patient must have adequate organ function.
    10) Patient has voluntarily agreed to participate by giving written informed consent/assent for the trial. The patient may also provide consent/assent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research.
    11) Female patient of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. The serum pregnancy test must be negative for the patient to be eligible.
    12) Female patients enrolled in the study, who are not free from menses for >2 years, post hysterectomy/oophorectomy, or surgically sterilized, must be willing to use either 2 adequate barrier methods or a barrier method plus a hormonal method of contraception to prevent pregnancy, or to abstain from heterosexual activity throughout the study, starting with Visit 1 through 120 days after the last dose of study drug. Approved contraceptive methods include 2 of the following methods (or 1 of the following methods combined with hormonal contraceptive), for example: intra-uterine device, diaphragm with spermicide, cervical cap with spermicide, male condoms, or female condom with spermicide. Spermicides alone are not an acceptable method of contraception.
    13) Male patients must agree to use an adequate method of contraception starting with Visit 1 through 120 days after the last dose of study drug.
    E.4Principal exclusion criteria
    1) Patient who has had chemotherapy, radioactive, or biological cancer therapy within 4 weeks prior to the first dose of study drug, or who has not recovered to CTCAE Grade 1 or better from the AEs due to cancer therapeutics administered more than 4 weeks earlier.
    2) Patient who received IPI only as an adjuvant therapy.
    3) Patient is currently participating or has participated in a study of an investigational agent or using an investigational device within 30 days of the first dose of study drug.
    4) Patient is expected to require any other form of systemic or localized antineoplastic therapy while on study.
    5) Patient is on chronic systemic steroid therapy (>10 mg/day prednisone or equivalent) within 2 weeks before the planned date for first dose randomized treatment or on any other form of immunosuppressive medication. (Patients that are expected to require premedication with corticosteroid for pembrolizumab will not be eligible for this study.)
    6) Patient has a known history of a hematologic malignancy, primary central nervous system (CNS) malignancy or sarcoma, or of another primary solid tumor, unless the patient has undergone potentially curative therapy with no evidence of that disease for 5 years.
    7) Patient has known active CNS metastases and/or carcinomatous meningitis.
    8) Patient previously had a severe hypersensitivity reaction to treatment with another mAb.
    9) Patient has an active autoimmune disease or a history of autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents. Patients with vitiligo or resolved childhood asthma/atopy would be exceptions to this rule. Patients that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Patients with hypothyroidism stable on hormone replacement will not be excluded from the study.
    10) Patients who received treatment with live vaccines within 30 days prior to the first dose of study medication. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, seasonal flu, H1N1 flu, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine.
    11) Patient had prior treatment with any other anti-PD-1, or PD-L1 or PD-L2 agent.
    12) Patient has previously participated in Merck pembrolizumab clinical trials.
    13) Patient has an active infection requiring systemic therapy.
    14) Patient has known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
    15) Patient is positive for active Hepatitis B (HBsAg reactive) or Hepatitis C (HCV ribonucleic acid [RNA] [qualitative] is detected). Patients with negative Hepatitis C antibody testing may not require RNA testing if deemed appropriate by treating physician.
    16) Patient has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient’s participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating investigator.
    17) Patient has known psychiatric or substance abuse disorders that would interfere with cooperation requirements of the trial.
    18) Patient is, at the time of signing informed consent, a regular user (including “recreational use”) of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol).
    19) Patient is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the Pre-screening or Screening visit through 120 days after the last dose of study medication.
    E.5 End points
    E.5.1Primary end point(s)
    Progression-free survival; Overall survival
    E.5.1.1Timepoint(s) of evaluation of this end point
    This clinical trial has fulfilled the primary endpoint requirements. The final analysis for these endpoints has been completed.
    E.5.2Secondary end point(s)
    Overall response rate
    Response duration
    E.5.2.1Timepoint(s) of evaluation of this end point
    This clinical trial has fulfilled all endpoint requirements.
    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 Yes
    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 trial2
    E.8.3 The trial involves single site in the Member State concerned Information not present in EudraCT
    E.8.4 The trial involves multiple sites in the Member State concerned Information not present in EudraCT
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA33
    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
    Argentina
    Australia
    France
    Germany
    Israel
    Italy
    Netherlands
    Norway
    Spain
    Sweden
    Switzerland
    United States
    E.8.7Trial has a data monitoring committee Yes
    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 years
    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 years2
    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: 300
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 210
    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 state
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 271
    F.4.2.2In the whole clinical trial 510
    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)
    None.
    After the study has achieved its key objective or the study has ended, the patient is discontinued from this study and will 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 Decision2012-12-21
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2012-12-19
    P. End of Trial
    P.End of Trial StatusCompleted
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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
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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