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    The EU Clinical Trials Register currently displays   43845   clinical trials with a EudraCT protocol, of which   7282   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:2018-000224-34
    Sponsor's Protocol Code Number:MK-3475-811
    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:2018-07-02
    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 number2018-000224-34
    A.3Full title of the trial
    A Phase III, Randomized, Double-blind Trial Comparing Trastuzumab Plus Chemotherapy and Pembrolizumab With Trastuzumab Plus Chemotherapy and Placebo as First-line Treatment in Participants With HER2 Positive Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (KEYNOTE 811)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase III, Randomized, Double-blind Trial Comparing Trastuzumab Plus Chemotherapy and Pembrolizumab With Trastuzumab Plus Chemotherapy and Placebo as First-line Treatment in Participants With HER2 Positive Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (KEYNOTE 811)
    A.4.1Sponsor's protocol code numberMK-3475-811
    A.5.4Other Identifiers
    Name:INDNumber:123 482
    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 Trial Operations
    B.5.3 Address:
    B.5.3.1Street AddressOne Merck Drive P.O. Box 100 Whitehouse Station
    B.5.3.2Town/ cityNew Jersey
    B.5.3.3Post code08889-0100
    B.5.3.4CountryFrance
    B.5.4Telephone number+12673056836
    B.5.6E-mailchie-schin.shih@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.3.9.4EV 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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for infusion
    D.8.4Route of administration of the placeboIntravenous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    HER2 Positive Advanced Gastric or Gastroesophageal Junction Adenocarcinoma
    E.1.1.1Medical condition in easily understood language
    Cancer of the stomach and lower esophagous
    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 LLT
    E.1.2Classification code 10071114
    E.1.2Term Metastatic gastric adenocarcinoma
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To compare PFS between treatment groups
    To compare overall survival (OS) between treatment groups.
    E.2.2Secondary objectives of the trial
    To compare Objective Response Rate (ORR) between treatment groups.
    To estimate Duration of Response (DOR), per RECIST 1.1 as assessed by BICR for each treatment group.
    To assess the safety and tolerability of pembrolizumab in combination with trastuzumab plus chemotherapy by proportion of adverse events (AEs)
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Future Biomedical Research
    E.3Principal inclusion criteria
    1. Male/female participants who are at least 18 years of age on the day of signing the informed consent with histologically or cytologically confirmed diagnosis of previously untreated, locally advanced unresectable or metastatic HER2 positive
    gastric or GEJ adenocarcinoma.
    2. Be HER2-positive defined as either IHC 3+ or IHC 2+ in combination with ISH+ (or FISH), as assessed by central review on primary or metastatic tumor. ISH positivity is defined as a ratio of ≥ 2.0 for the number of HER2 gene copies to the number of
    signals for CEP17.
    3. Have measurable disease as defined by RECIST 1.1 as determined by the site investigator. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
    Note: The exact same image acquisition and processing parameters should be used throughout the study.
    4. A male participant must agree to use an adequate method of contraception as outlined in Appendix 3 of the Protocol, for the course of the study through 180 days after the last dose of all study treatments.
    5. A female participant is eligible to participate if she is not pregnant (see Appendix 3 of the Protocol), not breastfeeding, and at least one of the following conditions applies:
    a.) Not a woman of childbearing potential (WOCBP) as defined in Appendix 3
    OR
    b.) A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 180 days after the last dose of study treatment.
    6. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial. The participant may also provide consent for Future Biomedical Research. However the participant may participate in the main study without participating in Future Biomedical Research.
    7. Have a performance status of 0 or 1 on the ECOG Performance Scale within 3 days prior to the first dose of trial treatment.
    8. Have a life expectancy of greater than 6 months.
    9. Participants must have a 12-lead electrocardiogram (ECG) and echocardiogram (ECHO) or multigated acquisition (MUGA) scan performed by the investigator or other qualified person to evaluate cardiac function prior to enrollment in the study.
    Adequate cardiac function will be assessed by:
    a) Left ventricular ejection fraction (LVEF) ≥ 55% as determined by MUGA scan or ECHO; and
    b) QT interval calculated according to the Fridericia method (QTcF) value ≤480 msec (mean of 3 measurements corrected for heart rate using Fridericia’s formula).
    10. Have provided tumor tissue sample deemed adequate for PD-L1 biomarker analysis. The PD-L1 result must be determined as positive or negative.
    11. Have adequate organ function as defined in the Table 2 in the Protocol. Specimens must be collected within 10 days prior to the start of study treatment.
    E.4Principal exclusion criteria
    1. Has had previous therapy for locally advanced unresectable or metastatic gastric/GEJ cancer. Participants may have received prior neoadjuvant or adjuvant therapy as long as it was completed at least 6 months prior to randomization without progression.
    2. Has had major surgery, open biopsy or significant traumatic injury within 28 days prior to randomization, or anticipation of the need for major surgery during the course of study treatment.
    3. Has had radiotherapy within 14 days of randomization. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
    4. Has a known additional malignancy that is progressing or has required active treatment within the past 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
    5. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, ie, without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
    6. Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, 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 and is allowed.
    7. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of trial drug.
    8. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
    9. Has a known history of active tuberculosis (TB; Mycobacterium tuberculosis).
    11. Has poorly controlled diarrhea (eg, watery stool, uncontrollable bowel movement with drugs, Grade ≥ 2 and number of defecations, ≥ 5/day).
    12. Accumulation of pleural, ascitic, or pericardial fluid requiring drainage within 2 weeks prior to enrollment.
    13. Has a history or current evidence of any condition (eg, known deficiency of the enzyme dihydropyrimidine dehydrogenase, hearing impairment, etc.), therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant’s participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
    14. Has peripheral neuropathy > Grade 1.
    15. Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial.
    16. A WOCBP who has a positive urine pregnancy test within 72 hours prior to randomization or treatment allocation (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
    17. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 180 days after the last dose of trial treatment.
    18. Has symptomatic congestive heart failure (CHF) (ie, New York Heart Association > Class II or higher), history or current evidence of clinically significant cardiac arrhythmia requiring anti-arrhythmic therapy other than beta blockers or digoxin and/or conduction abnormality ≤6 months prior to start of study treatment except atrial fibrillation and paroxysmal supraventricular tachycardia, active coronary artery disease, unstable angina (anginal symptoms at rest), new-onset angina within 3 months before randomization, or myocardial infarction ≥6 months before randomization.
    19. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). No testing for HIV is required unless mandated by local health authority.
    20. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. No testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
    21. Has severe hypersensitivity (≥Grade 3) to any pembrolizumab excipients.
    22. Has had an allogeneic tissue/solid organ transplant.
    23. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137)

    E.5 End points
    E.5.1Primary end point(s)
    (FPS) The time from randomization to the first documented disease
    progression or death due to any cause, whichever occurs first
    (OS) The time from randomization to death due to any cause
    E.5.1.1Timepoint(s) of evaluation of this end point
    Primary end points are Progression-free Survival (PFS) and Overall survival (OS).
    -IA2:
    Timing: to be performed after ~ 542 PFS events have occurred AND ~ 9 months after last participant randomized.
    Primary purpose: efficacy analysis for PFS and OS.
    -IA3:
    Timing: to be performed when at least 18 months after the last participant has been randomized AND at least 606 PFS events have been observed. This is the final PFS analysis.
    Primary purpose: efficacy analysis for PFS and OS.
    - Final analysis:
    Timing: to be performed when at least 28 months after the last participant has been randomized AND at least ~551 deaths have occurred.
    Primary purpose: efficacy analysis for OS.
    E.5.2Secondary end point(s)
    Objective Response: Complete response (CR) or partial response (PR)
    DOR: For participants who demonstrate CR or PR, DOR is defined as the time
    from first documented evidence of CR or PR until disease progression or death
    due to any cause, whichever occurs first.
    - Adverse events
    - Discontinuation of study treatment due to AEs
    E.5.2.1Timepoint(s) of evaluation of this end point
    Secondary efficacy Objective Response.
    - IA1:
    Timing: to be performed when ~ 260 participants have been followed up for ~ 8.5 months.
    Primary purpose: efficacy and futility analysis for ORR
    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 No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    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) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    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 Yes
    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 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 concerned9
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA85
    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
    Brazil
    Chile
    China
    France
    Germany
    Guatemala
    Ireland
    Israel
    Italy
    Japan
    Korea, Republic of
    New Zealand
    Poland
    Russian Federation
    Spain
    Turkey
    Ukraine
    United Kingdom
    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
    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: 366
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 366
    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 No
    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 state30
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 338
    F.4.2.2In the whole clinical trial 732
    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 will be followed every 6 weeks with imaging until disease progression. After disease progression subjects will be followed for survival by telephone every 12 weeks
    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 Decision2018-08-21
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-10-15
    P. End of Trial
    P.End of Trial StatusOngoing
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