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    Summary
    EudraCT Number:2014-002447-18
    Sponsor's Protocol Code Number:MK3475-055
    National Competent Authority:Denmark - DHMA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2015-06-16
    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 ConcernedDenmark - DHMA
    A.2EudraCT number2014-002447-18
    A.3Full title of the trial
    A Phase II Clinical Trial of Single Agent Pembrolizumab (MK-3475) in Subjects with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) Who Have Failed Platinum and Cetuximab
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Phase II Clinical Trial of MK-3475 in subjects with refractory HNSCC
    A.3.2Name or abbreviated title of the trial where available
    Phase II Clinical Trial of MK-3475 in subjects with refractory HNSCC
    A.4.1Sponsor's protocol code numberMK3475-055
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT02255097
    A.5.4Other Identifiers
    Name:KEYNOTE 055Number:-
    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 MK3475
    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
    Recurrent/metastatic head and neck squamous cell carcinoma
    E.1.1.1Medical condition in easily understood language
    Recurrent/metastatic head and neck squamous cell carcinoma
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    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.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the following in patients with R/M HNSCC who have progressed on platinum and cetuximab therapy: (1) To determine the safety and tolerability of 200 mg Q3W dose of MK-3475, (2) To evaluate anti-tumor activity of pembrolizumab (MK-3475) by objective response rate (ORR) using RECIST 1.1 assessed by independent radiology review, and (3) To evaluate anti-tumor activity of MK-3475 by ORR using RECIST 1.1 assessed by independent radiology review in subjects with PD-L1 strong positive.
    E.2.2Secondary objectives of the trial
    In subjects with R/M HNSCC who have progressed on platinum and cetuximab therapy:
    1) To evaluate anti-tumor activity of MK-3475 by ORR using RECIST 1.1 in subjects with PD -L1 +
    2) To estimate the response duration based on RECIST 1.1 in all subjects and separately in PD-L1 strong + subjects and in PD-L1 + subjects receiving MK-3475
    3) To estimate anti-tumor activity separately in all subjects, in PD-L1 strong + subjects, and in PD-L1 and all PD-L1 + subjects receiving MK-3475 by ORR using modified RECIST 1.1
    4) To estimate the anti-tumor activity of MK-3475 by ORR using RECIST 1.1 in all subjects with HPV +
    5) To estimate PFS using RECIST 1.1 separately in all subjects, in PD-L1 strong + subjects, and in all PD-L1 + subjects receiving MK-3475
    6) To estimate the overall survival (OS) separately in all subjects, in PD-L1 strong + subjects, and in all PD-L1 + subjects receiving MK-3475
    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.
    Pharmacokinetics: Pharmacokinetics (PK) of pembrolizumab when pembrolizumab is administered intravenously as monotherapy and in combination with chemotherapy will be evaluated. Objective: To investigate the relationship between candidate efficacy/resistance biomarkers and anti-tumor activity of pembrolizumab (MK-3475) utilizing pre- treatment tumor biopsies and blood sampling.
    E.3Principal inclusion criteria
    ­Be greater or equal to 18 years of age on day of signing informed consent
    ­Have histologically or cytologically-confirmed recurrent or metastatic head and neck squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx that is considered incurable by local therapies.
    ­Be resistant to platinum (either cisplatin or carboplatin) and cetuximab-based therapy. Resistance is defined as tumor progression or recurrence within 6 months of the last dose of platinum and cetuximab therapy in the adjuvant (e.g. with radiation after surgery), primary (e.g. with radiation), recurrent, or metastatic setting. Subject must be resistant to both platinum and cetuximab.
    ­Have provided tissue for PD-L1 biomarker analysis from a newly obtained core or excisional biopsy.
    ­Have measurable disease based on RECIST 1.1 as determined by central review.
    ­Have a performance status of 0 or 1 on the ECOG Performance Scale.
    E.4Principal exclusion criteria
    ­Has disease that is suitable for local therapy administered with curative intent.
    ­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 had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1
    ­Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1
    ­Has a known additional malignancy that is progressing or requires active treatment.
    ­Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
    ­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).
    ­Has active, non-infectious pneumonitis.
    ­Has an active infection requiring systemic therapy.
    ­Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or if the patient has previously participated in Merck MK-3475 clinical trials.
    ­Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
    ­Has known active Hepatitis B or Hepatitis C.
    ­Has received a live vaccine within 30 days of planned start of study therapy.
    E.5 End points
    E.5.1Primary end point(s)
    Objective response rate (ORR) as determined by a central independent radiology review. ORR will be evaluated separately in all subjects and the subset of all PD-L1 positive subjects.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Objective response rate (ORR) is defined as the proportion of subjects in the analysis population who have complete response (CR) or partial response (PR) using RECIST 1.1 criteria at any time during the study.
    E.5.2Secondary end point(s)
    ORR in all subjects with any PD-L1 positive.
    Other key secondary efficacy endpoints that will be evaluated in all subjects, all PD-L1 positive subjects, and all PD-L1 strong positive subjects include:
    Duration of Response
    ORR by modified RECIST 1.1
    ORR among HPV positive subjects
    Progression-free survival (PFS)
    Overall survival (OS)
    E.5.2.1Timepoint(s) of evaluation of this end point
    -Duration of Response: defined as time from first RECIST 1.1 response to disease progression in subjects who achieve a PR or better
    -ORR by modified RECIST 1.1: defined as proportion of subjects with a CR or PR using modified RECIST 1.1 criteria as defined in the Protocol.
    -ORR among HPV positive subjects: defined as the proportion of subjects with HPV positive tumor biopsy who achieve a CR or PR according to RECIST 1.1 criteria.
    -Progression-free survival (PFS): defined as the time from allocation to the first documented disease progression according to RECIST 1.1 or death due to any cause, whichever occurs first.
    -Overall survival (OS): defined as the time from allocation to death due to any cause.
    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 Yes
    E.6.7Pharmacodynamic Yes
    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 Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.4.1Number of sites anticipated in Member State concerned1
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA2
    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
    United States
    Denmark
    Norway
    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 years6
    E.8.9.1In the Member State concerned months4
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years7
    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: 75
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 75
    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 state2
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 6
    F.4.2.2In the whole clinical trial 150
    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)
    Subjects who progress while on study treatment may pursue another treatment option according to local standards. Subjects who stop pembrolizumab with Stable Disease or better may be eligible for up to one year of additional MK-3475 therapy if certain criteria are met.
    Once subjects have achieved the trial objective or the trial has ended, subjects are discontinued from this trial and will be enrolled in an extension trial 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 Decision2015-06-16
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-05-26
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2021-06-18
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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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