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    Summary
    EudraCT Number:2017-002567-17
    Sponsor's Protocol Code Number:8951-CL-0301
    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:2018-05-16
    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 number2017-002567-17
    A.3Full title of the trial
    A Phase 3, Global, Multi-Center, Double-Blind, Randomized, Efficacy Study of IMAB362 Plus mFOLFOX6 Compared with Placebo Plus mFOLFOX6 as First-line Treatment of Subjects with Claudin (CLDN)18.2-Positive, HER2-Negative, Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma
    Étude internationale de phase 3, multicentrique, randomisée, en double aveugle, comparant l’efficacité du traitement par IMAB362 plus mFOLFOX6 par rapport à un traitement par placebo plus mFOLFOX6 en première ligne chez des patients présentant un adénocarcinome de l’estomac ou de la jonction œsogastrique (JOG) Claudine (CLDN)18.2-positif, HER2-négatif, localement avancé inopérable ou métastatique
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase 3, Global, Multi-Center, Double-Blind, Randomized, Efficacy Study of IMAB362 Plus mFOLFOX6 Compared with Placebo Plus mFOLFOX6 as First-line Treatment of Subjects with Claudin (CLDN)18.2-Positive, HER2-Negative, Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma
    Étude internationale de phase 3, multicentrique, randomisée, en double aveugle, comparant l’efficacité du traitement par IMAB362 plus mFOLFOX6 par rapport à un traitement par placebo plus mFOLFOX6 en première ligne chez des patients présentant un adénocarcinome de l’estomac ou de la jonction œsogastrique (JOG) Claudine (CLDN)18.2-positif, HER2-négatif, localement avancé inopérable ou métastatique
    A.3.2Name or abbreviated title of the trial where available
    SPOTLIGHT
    A.4.1Sponsor's protocol code number8951-CL-0301
    A.5.4Other Identifiers
    Name:INDNumber: 129598
    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 SponsorAstellas Pharma Global Development, Inc. (APGD)
    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 supportAstellas Pharma Global Development, Inc. (APGD)
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAstellas Pharma Europe B.V.
    B.5.2Functional name of contact pointService Desk - Global Clinical Dev.
    B.5.3 Address:
    B.5.3.1Street AddressSylviusweg 62
    B.5.3.2Town/ cityLeiden
    B.5.3.3Post code2333 BE
    B.5.3.4CountryNetherlands
    B.5.4Telephone number+31715455878
    B.5.5Fax number+31715455224
    B.5.6E-mailcontacts@nl.astellas.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 Yes
    D.2.5.1Orphan drug designation numberEU/3/10/803
    D.3 Description of the IMP
    D.3.1Product nameIMAB362
    D.3.2Product code IMAB362
    D.3.4Pharmaceutical form Powder for concentrate for 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 INNZolbetuximab (recommended)
    D.3.9.1CAS number 1496553-00-4
    D.3.9.2Current sponsor codeIMAB362
    D.3.9.3Other descriptive nameIMAB362
    D.3.9.4EV Substance CodeSUB190351
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    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) No
    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
    Claudin (CLDN)18.2-Positive, HER2-Negative, Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma
    Adénocarcinome de l’estomac ou de la jonction œsogastrique (JOG) Claudine (CLDN)18.2-positif, HER2-négatif, localement avancé inopérable ou métastatique
    E.1.1.1Medical condition in easily understood language
    Metastatic Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma
    Adénocarcinome de l’estomac ou de la jonction œsogastrique (JOG) métastatique
    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 10001150
    E.1.2Term Adenocarcinoma gastric
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    to evaluate the efficacy of IMAB362 plus mFOLFOX6 compared with placebo plus mFOLFOX6 (as first-line treatment) as measured by PFS in subjects with Claudin (CLDN)18.2 positive, HER2–negative locally advanced unresectable or metastatic gastric and GEJ adenocarcinoma
    ·Évaluer l’efficacité de l’association d’IMAB362 plus mFOLFOX6 par rapport à l’association de placebo plus mFOLFOX6 (en traitement de première ligne), mesurée d’après la survie sans progression (SSP) chez des patients présentant un adénocarcinome de l’estomac ou de la jonction œsogastrique (JOG) Claudine (CLDN)18.2-positif, HER2 (récepteur 2 du facteur de croissance épithélial humain)-négatif, localement avancé inopérable ou métastatique
    E.2.2Secondary objectives of the trial
    -To evaluate efficacy as measured by Overall Survival (OS) as a key secondary objective
    -To evaluate efficacy as measured by Objective Response Rate (ORR)
    -To evaluate efficacy as measured by Duration of Response (DOR)
    -To evaluate safety and tolerability of IMAB362
    -To evaluate health related quality of life (HRQoL) using the parameters as measured by European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, QLQ-OG25, Global Pain (GP) and the EuroQOL Five Dimensions Questionnaire 5L (EQ5D-5L) questionnaires
    -To evaluate the pharmacokinetics of IMAB362
    -To evaluate the immunogenicity profile of IMAB362
    -Évaluer l’efficacité, mesurée d’après la survie globale (SG) comme objectif secondaire fondamental
    -Évaluer l’efficacité, mesurée d’après le taux de réponse objective (TRG)
    -Évaluer l’efficacité, mesurée d’après le taux de réponse objective (TRO)
    -Évaluer la tolérance et la sécurité d’emploi de l’IMAB362
    -Évaluer la qualité de vie (QdV) liée à la santé à l’aide des paramètres mesurés par les questionnaires QLQ-C30, QLQ-OG25, Douleur globale (GP, Global Pain) de l’Organisation européenne de recherche et de traitement du cancer (EORTC, European Organization for Research and Treatment of Cancer) et le questionnaire EQ5D-5L à 5 dimensions et 5 niveaux (EuroQOL Five Dimensions Questionnaire 5L)
    -Évaluer la pharmacocinétique de l’IMAB362
    -Évaluer le profil d’immunogénicité de l’IMAB362
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    General Criteria:
    1.Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written informed consent and privacy language as per national regulations (e.g., HIPAA Authorization for US sites) must be obtained from the subject or legally authorized representative (if applicable) prior to any study-related procedures.
    2.Subject is considered an adult (e.g., ≥ 18 years of age in the US) according to local regulation at the time of signing the informed consent.
    3.Subject agrees not to participate in another interventional study while on study treatment.
    4.Female subject must either:
    Be of non-childbearing potential:
    -postmenopausal (defined as at least 1 year without any menses for which there is no other obvious pathological or physiological cause) prior to Screening, or
    -documented surgically sterile (e.g., hysterectomy, bilateral salpingectomy,
    bilateral oophorectomy)
    Or, if of childbearing potential:
    -agree not to try to become pregnant during the study and for 6 months after the final study treatment administration,
    and, have a negative serum pregnancy test at Screening, (Note: Subjects with elevated serum beta human chorionic gonadotropin (βhCG) and a demonstrated non-pregnant status through additional testing are eligible), and if heterosexually active, agree to consistently use 1 form of highly effective birth control* starting at Screening and throughout the study period and for 6 months after the final study drug administration.
    5.Female subject must agree not to breastfeed starting at Screening and throughout the study period, and for 6 months after the final study treatment administration.
    6.Female subject must not donate ova starting at Screening and throughout the study period, and for 6 months after the final study drug administration.
    7.A sexually active male subject with female partner(s) who are of childbearing potential is eligible if:
    -Agree to use a male condom starting at screening and continue throughout study treatment and for 6 months after the final study drug administration.
    -If he has not had a vasectomy or is not sterile as defined below, his female partner(s) is utilizing 1 form of highly effective birth control starting at Screening and continue throughout study treatment and for 6 months after the he receives his final study drug administration.
    8.Male subject must not donate sperm starting at Screening and throughout the study period and for 6 months after the final study drug administration.
    9.Male subject with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy or for the time partner is breastfeeding throughout the study period and for 6 months after the final study drug administration.
    Disease Specific Criteria:
    10.Subject has histologically confirmed diagnosis of Gastric or GEJ adenocarcinoma.
    11.Subject has radiologically confirmed locally advanced unresectable or metastatic disease within 28 days prior to the first dose of study treatment.
    12.Subject has measurable disease according to RECIST 1.1 within 28 days prior to the first dose of study treatment. For subjects with only 1 measurable lesion and prior radiotherapy, the lesion must be outside the field of prior radiotherapy or must have documented progression following radiation therapy.
    13.Subject’s tumor expresses CLDN18.2 in ? 75% of tumor cells demonstrating moderate to strong membranous staining as determined by central IHC testing.
    14.Subject has a HER2-Negative tumor as determined by local or central testing on a gastric or GEJ tumor specimen.
    Physical or Laboratory Findings
    15.Subject has ECOG performance status 0 to 1.
    16.Subject has predicted life expectancy  12 weeks in the opinion of the investigator.
    17.Subject must meet all of the following criteria based on the centrally analyzed laboratory tests within 14 days prior to the first dose of study treatment. In case of multiple laboratory data within this period, the most recent data should be used to determine eligibility.
    -Hemoglobin (Hgb) >= 9 g/dL. NOTE: subject must not have received any growth factor or blood transfusions within 14 days prior to the hematology values obtained at screening. Subjects requiring transfusions to meet eligibility criteria are not eligible.
    -Absolute neutrophil count (ANC) >= 1.5 x 109/L
    -Platelets >=100 x 109/L
    -Albumin >= 2.5 g/dL
    -Total bilirubin < 1.5 x upper limit of normal (ULN)
    -Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x
    ULN without liver metastases (or ≤ 5 x ULN if liver metastases are present)
    -Either serum creatinine ≤ 1.5 x ULN or estimated glomerular filtration rate ? 45 mL/min/1.73 m2
    -PT/international normalized ratio (INR) and PTT ≤ 1.5 x ULN (except for subjects receiving anticoagulation therapy)
    E.4Principal exclusion criteria
    Prohibited Treatment or Therapies
    1.Subject has received prior systemic chemotherapy for locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma. However, subject may have received either neo-adjuvant or adjuvant chemotherapy as long as it was completed at least 6 months prior to the first dose of study treatment.
    2.Subject has received radiotherapy for locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma unless the radiotherapy was completed within28 days prior to start of study treatment. Subject who received palliative radiotherapy to peripheral bone metastases >=14 days prior to start of study treatment and has recovered from all acute toxicities is allowed.
    3.Subject has received systemic immunosuppressive therapy, including systemic corticosteroids within 14 days prior to first dose of study treatment. Subjects using a physiologic replacement dose of hydrocortisone or its equivalent (defined as up to 30 mg per day of hydrocortisone or up to 10 mg per day of prednisone) are allowed.
    4.Subject has received other investigational agents or devices within 28 days prior to first dose of study treatment.
    Medical History or Concurrent Disease
    5.Subject has prior severe allergic reaction or intolerance to a monoclonal antibody, including humanized or chimeric antibodies.
    6.Subject has known immediate or delayed hypersensitivity, intolerance or contraindication to any component of study treatment.
    7.Subject has prior severe allergic reaction or intolerance to any component of mFOLFOX6.
    8.Subject has known dihydropyrimidine dehydrogenase deficiency.
    9.Subject has gastric outlet syndrome or persistent/recurrent vomiting.
    10.Subject with recent gastric bleeding or symptomatic subjects with proven gastric ulcers that would exclude the subject from participation per investigator judgment.
    11.Subject has a known history of a positive test for human immunodeficiency virus (HIV) infection or known active hepatitis B (positive HBs Ag) or C infection. For subjects who are negative for HBs Ag, but HBc Ab positive, an HB DNA test will be performed and if positive the subject will be excluded. Subjects with positive serology but negative HCV RNA test results are eligible.
    12.Subject has an active autoimmune disease that has required systemic treatment within the past 2 years.
    13.Subject has active infection requiring systemic therapy that has not completely resolved within 14 days prior to start of study treatment.
    14.Subject has significant cardiovascular disease, including:
    -Congestive heart failure (defined as New York Heart Association Class III or IV), myocardial infarction, unstable angina, coronary angioplasty, stenting, coronary artery bypass graft, cerebrovascular accident or hypertensive crisis within 6 months prior to administration of first dose of study drug.
    -History of clinically significant ventricular arrhythmias (i.e., sustained ventricular tachycardia, ventricular fibrillation or Torsades de Pointes);
    -QTc interval > 450 msec
    -Cardiac arrhythmias requiring anti-arrhythmic medications (Subject with rate controlled atrial fibrillation for > 1 month prior to first dose of study drugs are eligible)
    15.Subject has known active central nervous system metastases and/or carcinomatous meningitis.
    16.Subject has known peripheral sensory neuropathy > Grade 1 unless the absence of deep tendon reflexes is the sole neurological abnormality.
    17.Subject has had a major surgical procedure and has not completely recovered within 28 days prior to the start of study treatment.
    18.Subject has psychiatric illness or social situations that would preclude study compliance, per investigator judgment.
    19.Subject has another malignancy for which treatment is required per investigator’s clinical judgment.
    20.Subject has any concurrent disease, infection or comorbid condition that interferes with the ability of the subject to participate in the study, which places the subject at undue risk or complicates the interpretation of data in the opinion of the investigator.

    Traitement ou thérapies interdit(e)s:
    1.Antécédents de chimiothérapie systémique pour un cancer de l’estomac ou de la JOG localement avancé inopérable ou métastatique. Cependant, le (la) patient(e) peut avoir reçu une chimiothérapie néoadjuvante ou adjuvante s’il (si elle) a terminé ce traitement au moins 6 mois avant la première dose de traitement à l’étude.
    2.Antécédents de radiothérapie pour un cancer de l’estomac ou de la JOG localement avancé inopérable ou métastatique dans les 28 jours précédant le début du traitement à l’étude. Les patients ayant reçu une radiothérapie palliative sur des métastases osseuses périphériques ? 14 jours avant le début du traitement à l’étude et ayant récupéré de toutes les toxicités aiguës sont autorisés à participer.
    3.Antécédents de traitement immunosuppresseur systémique, y compris corticoïdes systémiques dans les 14 jours précédant la première dose de traitement à l’étude. Les patients sous traitement de substitution à dose physiologique d’hydrocortisone ou de son équivalent (définie comme jusqu’à 30 mg par jour d’hydrocortisone ou jusqu’à 10 mg par jour de prednisone) sont autorisés à participer.
    4.Antécédents d’administration d’autres agents ou dispositifs à l’étude, dans les 28 jours précédant la première dose de traitement à l’étude.
    Antécédents médicaux/anamnèse et maladies concomitants:
    5.Antécédents de réaction allergique sévère ou d’intolérance à un anticorps monoclonal, y compris des anticorps humanisés ou chimériques.
    6.Antécédents connus d’hypersensibilité immédiate ou retardée, intolérance ou contre-indication à un des composants du traitement à l’étude.
    7.Antécédents de réaction allergique sévère ou d’intolérance à un des composants de mFOLFOX6.
    8.Déficit connu en dihydropyrimidine déshydrogénase.
    9.Sténose pylorique ou vomissements persistants/récurrents
    10.Hémorragie gastrique récente ou présence de symptômes chez des patients ayant des ulcères gastriques prouvés, pouvant exclure toute participation à l’étude, d’après le jugement de l’investigateur.
    11.Antécédents connus de résultat positif au dépistage de l’infection par le virus de l’immunodéficience humaine (VIH) ou présence connue d’une hépatite B active (AgHBs positif) ou d’une hépatite C active. Pour les patients ayant un résultat négatif pour l’AgHBs mais un résultat positif pour les AC anti-HBc, une analyse de l’ADN du VHB sera effectuée et si le résultat de cette analyse est positif, la participation du patient (de la patiente) ne sera pas autorisée. Les patients ayant une sérologie positive mais une analyse d’ARN du VHC négative sont éligibles.
    12.Maladie auto-immune active ayant nécessité un traitement systémique dans les 2 années précédentes.
    13.Infection active nécessitant un traitement systémique qui n’est pas complètement terminée dans les 14 jours précédant le début du traitement à l’étude.
    14.Maladie cardiovasculaire significative, incluant :
    ·Insuffisance cardiaque congestive (définie comme de Classe III ou IV selon la classification de la New York Heart Association), infarctus du myocarde, angor instable, angioplastie coronaire, pose d’endoprothèses coronaires (stents), pontage coronaire, accident vasculaire cérébral ou crise hypertensive dans les 6 mois précédant l’administration de la première dose de médicament à l’étude.
    ·Antécédents d’arythmies ventriculaires cliniquement significatives (c’est-à-dire, tachycardie ventriculaire prolongée, fibrillation ventriculaire ou torsades de pointes).
    ·Intervalle QTc > 450 msec.
    ·Arythmies cardiaques nécessitant des médicaments anti-arythmiques (les patients ayant une fibrillation auriculaire de fréquence contrôlée depuis > 1 mois avant la première dose de médicaments à l’étude sont éligibles)
    15.Présence connue de métastases actives du système nerveux central et/ou d’une méningite carcinomateuse.
    16.Neuropathie sensitive périphérique connue > grade 1, sauf si l’absence de réflexes ostéo-tendineux est la seule anomalie neurologique.
    17.Antécédents d’intervention chirurgicale majeure n’ayant pas totalement récupéré dans les 28 jours précédant le début du traitement à l’étude.
    18.Pathologie psychiatrique ou situation sociales susceptible d’interférer sur l’observance de l’étude, d’après le jugement de l’investigateur.
    19.Présence d’un autre cancer nécessitant un traitement, d’après le jugement clinique de l’investigateur.
    20.Présence concomitante d’une pathologie, infection ou comorbidité interférant sur la capacité du patient (de la patiente) à participer à l’étude, présentant un risque inutile pour le patient (la patiente) ou compliquant l’interprétation des données, d’après l’avis de l’investigateur.
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint is PFS, which is defined as the time from the date of randomization until the date of radiological PD (per Response Evaluation Criteria In Solid Tumors [RECIST] 1.1 by independent review committee [IRC]) or death from any cause, whichever is earliest.
    SSP, définie comme le temps écoulé entre la date de la randomisation et la date d’une PM radiologique (d’après l’évaluation du CEI selon les critères RECIST 1.1) ou du décès de quelque cause que ce soit, selon l’événement survenant en premier.
    E.5.1.1Timepoint(s) of evaluation of this end point
    The primary analysis will be performed when the protocol-defined number of PFS events have been observed.
    L'analyse primaire sera effectuée lorsque le nombre d'événements SSP défini par le protocole aura été observé.
    E.5.2Secondary end point(s)
    The secondary endpoints are:
    -OS, defined as the time from the date of randomization until the date of death from any cause
    -ORR, defined as the proportion of subjects who have a best overall response (BOR) of CR or PR as assessed by IRC per RECIST 1.1
    -DOR, defined as the time from the date of the first response (CR/PR) until the date of PD as assessed by IRC per RECIST 1.1 or date of death from any cause, whichever is earliest
    -Safety and tolerability, as measured by AEs, laboratory test results, vital signs, electrocardiograms (ECGs) and Eastern Cooperative Oncology Group (ECOG) performance status
    -HRQoL, as collected via EORTC QLQ-C30, QLQ-OG25, GP and EQ5D-5L questionnaires
    -Pharmacokinetics of IMAB362, Cmax and Ctrough
    -Immunogenicity of IMAB362 as measured by the frequency of anti-drug antibody (ADA) positive subjects.
    The exploratory endpoints are:
    -TTP, defined as the time from the date of randomization until the date of PD as assessed by IRC per RECIST 1.1.
    -PFS2, defined as the time from the date of randomization until the date of PD (per investigator) following subsequent anti-cancer therapy, death from any cause or start of any other anti-cancer therapy, whichever is earliest.
    -DCR, defined as the proportion of subjects who have a BOR of SD, CR or PR as assessed by IRC per RECIST 1.1.
    -Potential genomic and/or other exploratory biomarkers that may be related to treatment outcome of IMAB362
    -HRU
    Les critères d'évaluation secondaires:
    ·SG, définie comme le temps écoulé entre la date de la randomisation jusqu’à la date du décès, de quelque cause que ce soit.
    ·TRO, défini comme la proportion de patients ayant une meilleure réponse globale (MRG) ou une RC ou une RP, d’après l’évaluation du CEI selon les critères RECIST 1.1
    ·DdR, définie comme le temps écoulé entre la date de la première réponse (RC/RP) et la date d’une PM d’après l’évaluation du CEI selon les critères RECIST 1.1 ou la date du décès de quelque cause que ce soit, selon l’événement survenant en premier
    ·Tolérance et sécurité d’emploi, mesurées d’après les EI, les résultats des analyses biologiques, les signes vitaux, les ECG et le bilan de performances ECOG
    ·QdV liée à la santé (HRQoL), d’après les réponses aux questionnaires EORTC QLQ-C30, QLQ-OG25, GP et EQ5D-5L
    ·Pharmacocinétique de l’IMAB362, Cmax et Cmin
    ·Immunogénicité de l’IMAB362 d’après la mesure de la fréquence des patients ayant des anticorps anti-médicaments (AAM-positifs).
    Les critères d'évaluation exploratoires:
    ·TAP, défini comme le temps écoulé entre la date de la randomisation jusqu’à la date de la PM d’après l’évaluation du CEI selon les critères RECIST 1.1.
    ·Survie sans progression 2 (SSP2), définie comme le temps écoulé entre la date de la randomisation jusqu’à la date de la PM (d’après l’évaluation de l’investigateur) après un traitement anticancéreux ultérieur, la date du décès, de quelque cause que ce soit, ou l’instauration d’un autre traitement anticancéreux, selon l’événement survenant en premier.
    ·TCM, défini comme la proportion de patients ayant une MRG) de maladie stable (MS), RC ou une RP, d’après l’évaluation du CEI selon les critères RECIST 1.1
    ·Biomarqueurs génomiques et/ou autres potentiels susceptibles d’être corrélés au résultat du traitement par IMAB362
    ·HRU
    E.5.2.1Timepoint(s) of evaluation of this end point
    The secondary endpoint analysis will be performed at the protocol defined primary PFS analysis and at the final OS analysis after 100% of the planned death events have been observed.
    L'analyse d'évaluation secondaire sera effectuée à l'analyse SSP primaire définie par le protocole et à l'analyse finale SG après que 100% des événements de décès prévus ont été observés.
    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 Yes
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Immunogenicity
    Immunogénicité
    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.8.2.3.1Comparator description
    Chlorure de sodium à 0,9 % solution injectable
    0.9% Sodium Chloride Injection
    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 concerned12
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA60
    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
    Brazil
    Canada
    Chile
    China
    Colombia
    Costa Rica
    France
    Germany
    Israel
    Italy
    Japan
    Korea, Republic of
    Mexico
    Peru
    Poland
    Spain
    Taiwan
    United Kingdom
    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
    The end of study in all participating countries is defined as the last subject's last visit, or last contact.
    La fin des études dans tous les pays participants est définie comme la dernière visite du dernier sujet, ou dernier contact.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months5
    E.8.9.1In the Member State concerned days14
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months8
    E.8.9.2In all countries concerned by the trial days14
    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: 385
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 165
    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 state50
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 156
    F.4.2.2In the whole clinical trial 550
    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)
    After the end of participation in the trial, patients will receive treatment according to current local medical practice.
    Après la fin de la participation à l'essai, les patients recevront un traitement selon la pratique médicale locale actuelle.
    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 Decision2018-07-13
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-07-03
    P. End of Trial
    P.End of Trial StatusOngoing
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