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    Summary
    EudraCT Number:2013-005014-34
    Sponsor's Protocol Code Number:CLGX818A2202
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2014-04-16
    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 ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2013-005014-34
    A.3Full title of the trial
    A phase II, single arm, open-label, multicenter, study of oral LGX818 in patients with BRAF V600 mutant advanced non-small cell lung cancer that have progressed during or after at least one prior chemotherapy
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study evaluating novel BRAF inhibitor encorafenib (LGX818) when used as single agent in patients with advanced or metastatic BRAF V600 mutant non-small cell lung carcinoma.
    A.3.2Name or abbreviated title of the trial where available
    Not available
    A.4.1Sponsor's protocol code numberCLGX818A2202
    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 SponsorNOVARTIS FARMA S.p.A.
    B.1.3.4CountryItaly
    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 supportNovartis Pharma Services AG
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationNOVARTIS FARMA S.p.A
    B.5.2Functional name of contact pointDrug Regulatory Affairs
    B.5.3 Address:
    B.5.3.1Street AddressLargo Umberto Boccioni, 1
    B.5.3.2Town/ cityORIGGIO
    B.5.3.3Post code21040
    B.5.3.4CountryItaly
    B.5.4Telephone number+390296541
    B.5.5Fax number+39029659066
    B.5.6E-mailinfo.studiclinici@novartis.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 nameencorafenib
    D.3.2Product code LGX818
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNencorafenib
    D.3.9.1CAS number 1269440-17-6
    D.3.9.2Current sponsor codeLGX818
    D.3.9.3Other descriptive nameND
    D.3.9.4EV Substance CodeSUB32790
    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 Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    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 No
    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 nameencorafenib
    D.3.2Product code LGX818
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNencorafenib
    D.3.9.1CAS number 1269440-17-6
    D.3.9.2Current sponsor codeLGX818
    D.3.9.3Other descriptive nameND
    D.3.9.4EV Substance CodeSUB32790
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    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 No
    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
    Non-small cell lung cancer
    E.1.1.1Medical condition in easily understood language
    Lung cancer
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 16.1
    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 16.1
    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.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the efficacy of LGX818 as measured by Overall Response Rate (ORR) determined by investigator assessment.
    E.2.2Secondary objectives of the trial
    Key secondary:
    - To evaluate the efficacy of LGX818 as measured by ORR determined by BIRC.
    - To evaluate the treatment effect of LGX818 in terms of Progression-Free Survival (PFS) determined by investigator and BIRC.
    Other secondary:
    - To evaluate Duration of Response (DOR) and Disease Control Rate (DCR) by investigator and BIRC assessments.
    - To evaluate overall survival (OS)
    - To determine the safety and tolerability of LGX818
    - To characterize the pharmacokinetics of LGX818 in this patient population
    - To assess the concordance between the BRAF mutation status obtained using the investigational diagnostic test and the companion diagnostic assay which will be submitted for PMA.
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Title: To explore potential biomarkes
    date and version: 16.01.2014 - v00
    Objective: To explore potential biomarkes
    E.3Principal inclusion criteria
    - Male or female patients, age ≥ 18 years
    - Presence of BRAF V600E mutation in tumor tissue prior to study treatment, as determined by the specified investigational diagnostic test at a Novartis designated central laboratory
    - Histologically or cytologically confirmed diagnosis of Stage IIIB or IV NSCLC
    - At least one measurable lesion as defined by RECIST v1.1. A previously irradiated site lesion may only be counted as a target lesion if there is clear sign of progression since the irradiation
    - Patients must have progressed during or after at least one previous systemic, anti-cancer treatment for locally advanced or metastatic NSCLC.
    •Prior cytotoxic chemotherapy must include a platinum doublet.
    •(Neo-)adjuvant cytotoxic chemotherapy counts as one prior line of treatment if relapse occurred within 12 months from the end of the (neo-)adjuvant cytotoxic chemotherapy.
    - ECOG/World Health Organization (WHO) performance status 0-2
    Other protocol-defined inclusion criteria may apply
    E.4Principal exclusion criteria
    - Patients with symptomatic CNS metastases (neurologically unstable or required increasing doses of steroids within the 2 weeks prior to study entry)
    - History of leptomeningeal metastases (carcinomatous meningitis)
    - Prior therapy with a BRAF inhibitor
    - Patients who have received thoracic radiotherapy to lung fields ≤ 4 weeks prior to starting the study treatment or patients who have not recovered from radiotherapy-related toxicities. For all other anatomic sites (including radiotherapy to thoracic vertebrae and ribs) radiotherapy ≤ 2 weeks prior to starting the study treatment or who have not recovered from radiotherapy-related toxicities. Palliative radiotherapy for bone lesions ≤ 2 weeks prior to starting study treatment is allowed
    - Patients taking non-topical medication known to be a strong inhibitor of CYP3A4.However patients who either discontinue their treatment or switch to another medication at least three days prior to the first administration of LGX818 are eligible.
    - Patients who underwent major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic) within 4 weeks prior (2 weeks for resection of brain metastases) to starting study drug or who have not recovered from side effects of such procedures. Video-assisted thoracic surgery (VATS) and mediastinoscopy will not be counted as major surgery, and patients can be enrolled in the study ≥ 1 week after the procedure
    - Presence or history of a malignant disease other than NSCLC that has been diagnosed and/or required therapy within the past 3 years. Exceptions to this exclusion include the following: completely resected basal cell and squamous cell skin cancers, and completely resected carcinoma in situ of any type
    - Impaired cardiovascular function or clinically significant cardiovascular diseases
    - Uncontrolled arterial hypertension despite medical treatment
    - Patient is receiving unstable or increasing doses of corticosteroids. If patients are on corticosteroids for endocrine deficiencies or tumor-associated symptoms (non-CNS), dose must have been stabilized (or decreasing) for at least 5 days before first dose of study treatment

    Other protocol-defined exclusion criteria may apply
    E.5 End points
    E.5.1Primary end point(s)
    Overall Response Rate (ORR), calculated as the proportion of patients with a confirmed best overall response of Complete Response (CR) or Partial Response (PR) (RECIST version 1.1 criteria) per investigator.
    E.5.1.1Timepoint(s) of evaluation of this end point
    36 months
    E.5.2Secondary end point(s)
    Key secondary:
    1. ORR, calculated as the proportion of patients with a confirmed best overall response of Complete Response (CR) or Partial Response (PR) (RECIST version 1.1 criteria) per blinded independent review committee(BIRC).
    2. PFS, defined as time from start of treatment to date of first documented disease progression (as assessed by investigator/BIRC per RECIST version 1.1 criteria) or date of death due to any cause whichever occurs first.
    Other secondary:
    3. Duration of response (DOR), defined as the time from date of first documented CR or PR to date of first documented disease progression or death due to any cause whichever occurs first. Disease control rate (DCR), defined as the proportion of patients with best overall response of CR, PR or SD.
    4. Overall survival (OS), defined as time from start of treatment to date of death due to any cause.
    5. Safety: Adverse events and serious adverse events, changes in laboratory values, vital signs, ECGs, and assessment of physical, dermatological and ocular examinations graded according to the NCI CTCAE v4.03.
    6. Plasma concentration-time profiles of LGX818 (and appropriate individual PK parameters based on population PK modeling in a future pooled analysis). Trough concentrations of LGX818 and plasma 4-beta-hydroxycholesterol to account for the attainment of PK steady-state after auto-induction of CYP3A4.
    7. Concordance rate between BRAF mutation status obtained using the investigational diagnostic test and the companion diagnostic assay which will be submitted for PMA
    E.5.2.1Timepoint(s) of evaluation of this end point
    Key secondary:
    1 and 2= 36 months
    Other secondary:
    3 and 4 = 36 months
    5 = Continuous Monitoring until 30 days after EOT
    6 = Day 1, Day 22, Day 43, Day 64, Day 85 and Day 106
    7 = At the time of molecular pre-screening
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis Yes
    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) 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 No
    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 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 concerned10
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA30
    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
    Bulgaria
    Canada
    China
    France
    Italy
    Japan
    Netherlands
    Argentina
    Germany
    India
    Lebanon
    Spain
    Thailand
    Israel
    Mexico
    Russian Federation
    Singapore
    Switzerland
    Turkey
    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
    The end of study is defined as the final overall survival analysis timepoint. Based on the protocol assumptions, this is estimated to occur around 36 months.
    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 months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years3
    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: 19
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 39
    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 state10
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 30
    F.4.2.2In the whole clinical trial 58
    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)
    At the end of the study, access to LGX818 treatment will be made available to patients who continue to derive benefit from LGX818 study 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 Decision2014-04-24
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2014-05-15
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2014-05-12
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