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    Summary
    EudraCT Number:2015-003715-38
    Sponsor's Protocol Code Number:D4190C00006
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2016-02-24
    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 ConcernedUK - MHRA
    A.2EudraCT number2015-003715-38
    A.3Full title of the trial
    A Phase 1b Open-label Study to Evaluate the Safety and Tolerability of MEDI4736 in Combination with Tremelimumab in Subjects with Advanced Non-small Cell Lung Cancer
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A clinical trial in patients with Non-small Cell Lung Cancer that have not responded to previous treatment, to investigate the safety, tolerability, and clinical activity of the investigational drugs MEDI4736 (durvalumab) and tremelimumab. The study will look at the effect of these drugs given either as a single agent (MEDI4736 monotherapy) or as combination therapy (MEDI4736 given together with tremelimumab ).
    A.4.1Sponsor's protocol code numberD4190C00006
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT02000947
    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 SponsorMedImmune LLC
    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 supportMedImmune LLC
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMedImmune LLC
    B.5.2Functional name of contact pointAstraZeneca Study Info. Center
    B.5.3 Address:
    B.5.3.1Street AddressOne MedImmune Way
    B.5.3.2Town/ cityGaithersburg
    B.5.3.3Post code20878
    B.5.3.4CountryUnited States
    B.5.4Telephone number+1877240 9479
    B.5.6E-mailinformation.center@astrazeneca.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 namedurvalumab
    D.3.2Product code MEDI4736
    D.3.4Pharmaceutical form 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 INNDurvalumab
    D.3.9.1CAS number 1428935-60-7
    D.3.9.2Current sponsor codeMEDI4736
    D.3.9.3Other descriptive nameImmunoglobulin G1, anti-human CD antigen
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    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) 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.IMP: 2
    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 nametremelimumab
    D.3.2Product code MEDI1123
    D.3.4Pharmaceutical form 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 INNTremelimumab
    D.3.9.1CAS number 745013-59-6
    D.3.9.2Current sponsor codeMEDI1123
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Locally advanced or metastatic squamous or nonsquamous non- small cell lung cancer (NSCLC)
    E.1.1.1Medical condition in easily understood language
    NSCLC is a common type of lung cancer and can be defined as squamous or non-squamous, depending on the type of cells involved. Locally advanced or metastatic is cancer starting to spread.
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level PT
    E.1.2Classification code 10029520
    E.1.2Term Non-small cell lung cancer stage IIIA
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10029522
    E.1.2Term Non-small cell lung cancer stage IV
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10029521
    E.1.2Term Non-small cell lung cancer stage IIIB
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10066490
    E.1.2Term Progression of non-small cell lung cancer
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10059515
    E.1.2Term Non-small cell lung cancer metastatic
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10061873
    E.1.2Term Non-small cell lung cancer
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10029519
    E.1.2Term Non-small cell lung cancer stage III
    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
    Expansion Phase:
    Cohort B (sequential administration): determine antitumor activity of MEDI4736 in combination with tremelimumab in subjects who have received 1 prior line of treatment who are immunotherapy naïve, with non-EGFR mutation +ve/non-ALK rearrangement +ve, PD-L1-negative advanced non-squamous NSCLC
    Cohort C: determine the safety profile of MEDI4736/ tremelimumab combination at the recommended dose, using the Q4W dosing schedule in subjects with NSCLC who have received up to 3 prior lines of systemic therapy and failed PD-1/PD-L1 monotherapy
    Cohort C: determine antitumor activity of MEDI4736 in combination with tremelimumab at the recommended dose using Q4W dosing schedule in subjects with advanced NSCLC who have received up to 3 prior lines of systemic therapy and failed PD-1/PD-L1 monotherapy.
    Dose-expansion Cohorts: evaluate the safety profile of MEDI4736 monotherapy in subjects who have experienced irAEs after discontinuing MEDI4736 in combination with tremelimumab
    E.2.2Secondary objectives of the trial
    Cohort B (sequential admin):
    •Evaluate antitumor activity of the MEDI4736/tremelimumab recommended dose combination (Q4W schedule) in subjects with 1 prior line of treatment, non-EGFR mutation +ve/non-ALK rearrangement +ve advanced non-squamous NSCLC regardless of PD-L1 status
    •Determine the safety profile of the MEDI4736/tremelimumab combination in non-squamous NSCLC subjects
    •Evaluate candidate, predictive, and/or prognostic biomarkers in immunotherapy-naïve, non-EGFR mutation +ve/non-ALK rearrangement +ve, advanced non-squamous NSCLC subjects for correlation with MEDI4736/tremelimumab combination activity
    Cohort C: Evaluate antitumor activity of the MEDI4736/tremelimumab combination in advanced NSCLC subjects who failed PD-1/PD-L1 monotherapy
    PK of:
    •MEDI4736 in combination with tremelimumab
    •tremelimumab in combination with MEDI4736
    Determine the immunogenicity of MEDI4736 in combination with Tremelimumab and of tremelimumab in combination with MEDI473
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Age ≥ 18 years
    2. Histologically confirmed locally advanced or metastatic squamous or nonsquamous NSCLC
    3. ECOG performance status of 0 or 1
    4. At least 1 measurable lesion according to RECIST Version 1.1
    5. At least 1 lesion amenable to biopsy at screening
    6. Adequate organ and marrow function
    E.4Principal exclusion criteria
    1. Any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment
    2. Current or prior use of immunosuppressive medication within 14 days before the first dose of study drug
    3. Active or prior documented autoimmune disease within the last 2 years
    4. Major surgical procedure within 28 days prior to the first dose of study drug
    E.5 End points
    E.5.1Primary end point(s)
    Cohort C: The endpoints for safety will include adverse events (AEs), serious adverse events (SAEs), laboratory evaluations, vital signs, physical examinations, and electrocardiogram (ECG) results.

    Cohort B (sequential administration) and Cohort C: Objective response (OR) based on RECIST Version 1.1
    E.5.1.1Timepoint(s) of evaluation of this end point
    Cohort C: Safety Evaluations take place at Screening, Cycle 1 (Days 1,2, 8, 15 and 22) then Day 1 and Day 22 of each cycle through Cycle 13. ECG testing takes place at Screening, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 7 Day 1, and Cycle 13 Day 1

    Cohort B: Objective response as determined by radiographic disease assessment per RECIST Version 1.1 at Screening and every 8 weeks thereafter as per protocol
    E.5.2Secondary end point(s)
    The endpoints for assessment of antitumor activity include:
    ◦ Dose-expansion Cohort B (sequential administration) and Cohort C:
    - OR as determined by the investigator based on RECIST v1.1.
    - Duration of response (DoR), disease control (DC), and progression-free survival (PFS) based on
    RECIST v1.1 by investigator and BICR, and overall survival (OS).
    • Dose-expansion Cohort B (sequential administration)
    ◦ The endpoints for safety will include AEs, SAEs, laboratory evaluations, vital signs, physical
    examinations, and electrocardiogram (ECG) results.
    • The endpoints related to candidate predictive and/or prognostic biomarkers in dose-expansion Cohort B (sequential administration) are likely to focus on tissue-based, protein or gene expression measures and peripheral gene signatures including, but not limited to:
    ◦ PD-L1 expression / localization on tumor membrane and tumor-infiltrating immune cells within the
    tumor microenvironment
    ◦ IHC measures of markers associated with infiltrating immune cells (eg, Cluster of Differentiation 8)
    ◦ Gene expression signatures associated with adaptive response (eg, IFNGamma and related genes)
    • The endpoints for assessment of PK of MEDI4736 and tremelimumab include individual MEDI4736 and tremelimumab concentrations in serum and PK parameters including CmaxAUC), clearance, and half-life (t½).
    • The endpoints for assessment of immunogenicity of MEDI4736 and tremelimumab include the number and percentage of subjects who develop detectable ADAs.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Screening through 5 years after the last subject receives the first dose of study medication
    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 No
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E.7.1.3.1Other trial type description
    Phase 1b - including exploratory therapy.
    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 trial3
    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 concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA40
    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
    Canada
    France
    Germany
    Italy
    Korea, Republic of
    New Zealand
    Spain
    Taiwan
    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
    As per protocol: The end of the study (“study completion”) is defined as 5 years after the last subject begins treatment or the date the study is closed by the sponsor, whichever occurs first.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months1
    E.8.9.1In the Member State concerned days26
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months2
    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: 147
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 299
    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 state14
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 200
    F.4.2.2In the whole clinical trial 446
    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
    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 Decision2016-02-29
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-03-31
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2019-09-17
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