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    Summary
    EudraCT Number:2015-002354-12
    Sponsor's Protocol Code Number:CMBG453X2101
    National Competent Authority:Germany - PEI
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2016-03-22
    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 ConcernedGermany - PEI
    A.2EudraCT number2015-002354-12
    A.3Full title of the trial
    A phase I-Ib/II, open-label, multi-center study of the safety and efficacy of MBG453 as single agent and in combination with PDR001 in adult patients with advanced malignancies
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    An interventional study of MBG453 alone and in combination with PDR001 in patients with advanced malignancies
    A.4.1Sponsor's protocol code numberCMBG453X2101
    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 Pharma Services AG
    B.1.3.4CountrySwitzerland
    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 Pharma GmbH
    B.5.2Functional name of contact pointMedizinischer Infoservice (MCC)
    B.5.3 Address:
    B.5.3.1Street AddressRoonstrasse 25
    B.5.3.2Town/ cityNürnberg
    B.5.3.3Post code90429
    B.5.3.4CountryGermany
    B.5.4Telephone number+491802232300
    B.5.5Fax number+4991127312160
    B.5.6E-mailinfoservice.novartis@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.3.2Product code MBG453
    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 INNNot established yet
    D.3.9.2Current sponsor codeMBG453
    D.3.9.3Other descriptive nameMBG453
    D.3.9.4EV Substance CodeSUB178459
    D.3.10 Strength
    D.3.10.1Concentration unit mg/kg milligram(s)/kilogram
    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 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.3.2Product code PDR001
    D.3.4Pharmaceutical form Lyophilisate 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 INNNot established yet
    D.3.9.2Current sponsor codePDR001
    D.3.9.3Other descriptive namePDR001
    D.3.9.4EV Substance CodeSUB171710
    D.3.10 Strength
    D.3.10.1Concentration unit mg/kg milligram(s)/kilogram
    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 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
    Solid tumors
    E.1.1.1Medical condition in easily understood language
    Solid tumors
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Phase I/Ib part
    ● To characterize the safety and tolerability of MBG453 single agent and in combination with PDR001 and to identify recommended doses for future studies
    Phase I-Ib dose ranging part
    ● To further investigate the safety and tolerability of different doses of MBG453 alone or in combination with PDR001
    Phase II part
    ● To estimate anti-tumor activity of MBG453 alone and in combination with PDR001
    E.2.2Secondary objectives of the trial
    Phase I-Ib/II part
    ● To evaluate the preliminary ant-tumor activity of MBG453 single agent and in combination with PDR001
    ● To characterize the pharmacokinetic profile of MBG453 single agent and in combination with PDR001
    ● To assess emergence of anti-MBG453 and anti-PDR001 antibodies following one or more i.v. infusions of MBG453 single agent and in combination with PDR001
    ● To assess potential predictors of efficacy of MBG453 single agent and in combination with PDR001 in tumor sample
    ● To assess the pharmacodynamic effect of MBG453 single agent and in combination with PDR001 in tumor sample
    ● To describe the survival distribution of patients treated with MBG453 single agent and in combination with PDR001 for each disease group
    Phase II (combination):
    ● To make an initial comparison for MBG453 and PDR001 administered in combination on a Q2W and Q4W dosing schedules.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Histologically documented advanced or metastatic solid tumors.
    2. Phase I-Ib part (including dose ranging part): Patients with advanced/metastatic solid tumors, with measurable or non-measurable disease as determined by RECIST v1.1, who have progressed despite standard therapy or are intolerant of standard therapy, or for whom no standard therapy exists and who did not receive prior anti-PD1/PD-L1 treatment.
    3. Phase II part (MBG453 single agent): Patients with advanced/metastatic solid tumors in the indication in which at least one confirmed PR or CR was seen during the dose escalation phase I part. Patients must have measurable disease as determined by RECIST v1.1, have progressed despite standard therapy or be intolerant to standard therapy.
    4. Phase II part (MBG453 in combination PDR001): Patients with advanced/metastatic tumors in the below selected indications, with at least one measurable lesion as determined by RECIST v1.1, who have received standard therapy and are intolerant of standard therapy or have progressed following their last prior therapy.:
    • Melanoma (anti-PD-1/PD-L1 therapy naïve or pre-treated)
    • NSCLC (anti-PD-1/PD-L1 therapy naïve or pre-treated)
    • RCC (anti-PD-1/PD-L1 therapy naïve or pre-treated)
    5. Must have a site of disease amenable to biopsy, and be a candidate for tumor biopsy according to the treating institution’s guidelines. Patient must be willing to undergo a new tumor biopsy at screening/baseline, and during therapy on the study.
    Other protocol-defined inclusion criteria may apply.
    E.4Principal exclusion criteria
    1. Presence of symptomatic central nervous system (CNS) metastases.
    2. History of severe hypersensitivity reactions to other monoclonal antibodies (mAbs).
    3. Human Immunodeficiency Virus (HIV), HBV (Hepatitis B Virus) or HCV (Hepatitis C Virus) infection.
    4. Active autoimmune disease or a documented history of autoimmune disease, including ulcerative colitis and Crohn’s disease or any condition that requires systemic steroids.
    5. Systemic steroid therapy or any immunosuppressive therapy (≥10mg/day prednisone or equivalent).
    6. Use of any vaccines against infectious diseases (e.g. varicella, pneumococcus) within 4 weeks of initiation of study treatment.
    7. Pre-treatment with anti-CTLA4 antibodies in combination with any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathway.
    8. Participation in an interventional, investigational non-immunotherapy study within 2 weeks of the first dose of study treatment.
    9. Prior participation in an interventional, investigational cancer vaccine or immunotherapy study except for an anti-PD-1/PD-L1 study.
    Other protocol-defined exclusion criteria may apply.
    E.5 End points
    E.5.1Primary end point(s)
    Phase I/Ib parts:
    • The incidence and severity of Aes and SAEs, including changes in laboratory parameters, vital signs and ECGs
    • Dose interruptions, reductions and dose intensity
    • The incidence of DLTs during the first cycle of treatment with single agent MBG453
    • The incidence of DLTs during the first and second cycle of treatment with MBG453 in combination with PDR001
    Phase I-Ib dose ranging part:
    • Incidence and severity of AEs and SAEs, including changes in laboratory parameters, vital signs and ECGs
    • Dose interruptions, reductions and dose intensity
    Phase II part:
    • Overall response rate (ORR) per RECIST v1.1
    E.5.1.1Timepoint(s) of evaluation of this end point
    Phase I/Ib parts:
    • Up to 90 days after last dose or longer
    • During a treatment cycle (28 days)
    • End of cycle 1
    • End of cycle 1 and end of cycle 2
    Phase I-Ib dose ranging part:
    • Up to 90 days after last dose or longer
    • During a treatment cycle (28 days)
    Phase II part:
    • Every 8 weeks until week 40, and then every 12 weeks until progression of disease
    E.5.2Secondary end point(s)
    Phase I/Ib parts:
    • Best Overall Response (BOR), Progression Free Survival (PFS) and DOR per RECIST v1.1; ORR and PFS per irRC
    • Serum PK parameters (e.g., AUC, Cmax, Tmax, half-life); Serum concentration vs. time profiles
    • Presence and/or concentration of anti-MBG453 and anti-PDR001 antibodies
    • Assess potential associations between expression of PD-L1 and other immunological markers such as, but not restricted to TIM-3, CD8, FoxP3 and anti-tumor activity
    • Tumor Infiltrating Lymphocytes (TIL) counts and expression of immune-related genes (RNA/protein)
    • Overall survival (OS)
    Phase II part (combination):
    • Incidence and severity of AEs and SAEs, including changes in laboratory parameters, vital signs and ECGs
    • Dose interruptions, reductions and dose intensity
    • Serum PK parameters (e.g., AUC, Cmax, Tmax, half-life); Serum concentration vs. time profiles
    • ORR, BOR, PFS and DOR per RECIST v1.1; ORR and PFS per irRC
    E.5.2.1Timepoint(s) of evaluation of this end point
    Phase I/Ib parts:
    • Every 8 weeks until week 40, and then every 12 weeks until progression of disease
    • Cycle 1 and Cycle 3 Days 1,2,8,11 and 15. Cycles 2, 3, 4, 5 and 6 on Day 1, and end of treatment
    • Cycles 1 to 6 on Day 1 and end of treatment
    • Screening and after Cycle 3 Day 1
    • Screening and after Cycle 3 Day 1
    • From time of start treatment until the date of death
    Phase II part (combination):
    • Up to 90 days after last dose or longer
    • During a treatment cycle (28 days)
    • Cycle 1 and Cycle 3 Days 1,2,8,11 and 15. Cycles 2, 3, 4, 5 and 6 on Day 1, and end of treatment
    • Every 8 weeks until week 40, and then every 12 weeks until progression of disease
    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 No
    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 No
    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 Yes
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the 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 concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA6
    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
    Canada
    Germany
    Italy
    Korea, Republic of
    Netherlands
    Singapore
    Switzerland
    Taiwan
    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 the study will be when at least 80% of the patients have completed the survival follow-up period, or discontinued the study for any reason, and all patients have completed treatment as well as the 90 day safety follow-up period, or if the study is terminated early.
    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 months11
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years3
    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: 175
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 75
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state15
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 100
    F.4.2.2In the whole clinical trial 250
    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 Decision2016-08-15
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-08-09
    P. End of Trial
    P.End of Trial StatusCompleted
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
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