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    Summary
    EudraCT Number:2020-003657-30
    Sponsor's Protocol Code Number:DAY101-001
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Restarted
    Date on which this record was first entered in the EudraCT database:2020-10-09
    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 ConcernedGermany - BfArM
    A.2EudraCT number2020-003657-30
    A.3Full title of the trial
    FIREFLY-1: A Phase 2, Open-Label, Multicenter Study to Evaluate the Safety and Efficacy of the Oral Pan-RAF Inhibitor DAY101 in Pediatric Patients with RAF-Altered, Recurrent or Progressive Low-Grade Glioma and Advanced Solid Tumors
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase 2 Study to Test Effects of Using DAY101 in Children with Brain Cancer
    A.3.2Name or abbreviated title of the trial where available
    FIREFLY-1
    A.4.1Sponsor's protocol code numberDAY101-001
    A.5.4Other Identifiers
    Name:INDNumber:108340
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/442/2023
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorDay One Biopharmaceuticals, Inc. (Day One)
    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 supportDay One Biopharmaceuticals, Inc. (Day One)
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationParexel International (IRL) Limited
    B.5.2Functional name of contact pointMelissa Kenny
    B.5.3 Address:
    B.5.3.1Street Address70 Sir John Rogerson's Quay
    B.5.3.2Town/ cityDublin
    B.5.3.3Post code2
    B.5.3.4CountryIreland
    B.5.4Telephone number-
    B.5.6E-mailclinicaltrial.enquiries@parexel.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/3/21/2334
    D.3 Description of the IMP
    D.3.1Product nameTovorafenib
    D.3.2Product code DAY101
    D.3.4Pharmaceutical form Tablet
    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 INNTovorafenib
    D.3.9.1CAS number 1096708-71-2
    D.3.9.2Current sponsor codeDAY101
    D.3.9.3Other descriptive nameMLN2480, TAK-580, BSK1369, BIIB024, QHA01, C200601001-FP
    D.3.9.4EV Substance CodeSUB89679
    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.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 Yes
    D.2.5.1Orphan drug designation numberEU/3/21/2434
    D.3 Description of the IMP
    D.3.1Product nameTovorafenib
    D.3.2Product code DAY101
    D.3.4Pharmaceutical form Powder for oral suspension
    D.3.4.1Specific paediatric formulation Yes
    D.3.7Routes of administration for this IMPGastroenteral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTovorafenib
    D.3.9.1CAS number 1096708-71-2
    D.3.9.2Current sponsor codeDAY101
    D.3.9.3Other descriptive nameMLN2480, TAK-580, BSK1369, BIIB024,QHA01, C200601001-FP
    D.3.9.4EV Substance CodeSUB89679
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number300
    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
    RAF-Altered, Recurrent or Progressive Low-Grade Glioma and Advanced Solid Tumors in pediatric patients.
    E.1.1.1Medical condition in easily understood language
    Brain tumor in children and young adults
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Arm 1 (Low-Grade Glioma) To evaluate the efficacy of tovorafenib as measured by the overall response rate as determined by an ind. radiology review committee following treatment with tovorafenib in pediatric patients aged 6 months to 25 years, inclusive, with a relapsed or progressive low-grade glioma (LGG) harboring a known activating BRAF alteration.
    Arm 2 (Low-Grade Glioma Extension)
    To assess the safety and tolerability of DAY101 in pediatric patients aged 6 months to 25 years, incl., with a relapsed or progressive low-grade glioma harboring a known or expected to be activating RAF alteration.
    Arm 3 (Advanced Solid Tumor) To evaluate the preliminary efficacy of DAY101 as measured by the overall response rate (ORR) as determined by an independent radiology review committee (IRC) following treatment with DAY101 in pediatric
    patients aged 6 months to 25 years, inclusive, with a relapsed or progressive advanced solid tumor harboring a known or expected to be
    activating RAF fusion.
    E.2.2Secondary objectives of the trial
    Arm 1 (Low-Grade Glioma):
    - To assess safety and tolerability of DAY101
    - To determine the relationship between pharmacokinetics (PK) and drug effects, including efficacy and safety

    Arm 2 (Low-Grade Glioma Extension) :
    - To determine the ORR per Response Assessment in Neuro-Oncology
    (RANO) criteria as determined by 1) an IRC and 2) the treating investigator
    - To determine the ORR based on Response Assessment in Pediatric Neuro-Oncology (RAPNO)–low-grade glioma criteria as determined by an IRC

    Arm 3 (Advanced Solid Tumor)
    -To assess the safety and tolerability of DAY101 in pediatric patients with advanced solid tumors
    -To determine the relationship between PK and drug effects, including efficacy and safety

    For the complete list of secondary objectives please refer to the protocol Section 2 "Study Objectives".
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - Patients must be age 6 months to 25 years, inclusive, with:
    a) Arm 1 (Low-Grade Glioma): A relapsed or progressive low-grade glioma (LGG) with a documented known activating BRAF alteration.
    b) Arm 2 (Low-Grade Glioma Extension): A relapsed or progressive low-grade
    glioma with a documented known or expected to be activating BRAF mutation or RAF
    fusion.
    c) Arm 3 (Advanced Solid Tumor): Locally advanced or metastatic solid tumor with a documented known or expected to be activating RAF fusion.

    - Patients must have histopathologic verification of malignancy at either original diagnosis or relapse.

    - Must have received at least one line of prior systemic therapy and have documented evidence of radiographic progression

    - Patients must have evaluable and/or measurable disease as specified
    below:
    a) Arm 1 (Low-Grade Glioma):Must have at least one measurable lesion.
    b) Arm 2 (Low-Grade Glioma Extension): Must have evaluable and/or measurable disease
    c) Arm 3 (Advanced Solid Tumor): Must have at least one measurable lesion

    - Patients must have Karnofsky (those 16 years and older) or Lansky (those younger than 16 years) performance score of at least 50.
    For the complete list of the inclusion criteria, please refer to the protocol.
    E.4Principal exclusion criteria
    - Patient has symptoms of clinical progression without radiographically recurrent or radiographically progressive disease.
    - Patient has history of any major disease, other than the primary malignancy under study, that might interfere with safe protocol
    participation
    - Patient has major surgery within 14 days (two weeks) prior to C1D1
    - Patient has clinically significant active cardiovascular disease, or history of myocardial infarction, or deep vein thrombosis/pulmonary embolism within six months prior to C1D1
    - Patient is currently enrolled in any other investigational treatment study. Participation in a concurrent observational or bio-sampling study is allowed.

    For the complete list of the exclusion criteria, please refer to the protocol.
    E.5 End points
    E.5.1Primary end point(s)
    Arm 1 (Low-Grade Glioma):
    ORR by RANO-HGG criteria
    Arm 2 (Low-Grade Glioma Extension):
    Type, frequency, and severity of adverse events (AEs) and laboratory abnormalities
    Arm 3 (Advanced Solid Tumor):
    Measured by the proportion of patients with best overall confirmed response of complete response (CR) or partial response (PR) by RECIST v1.1 criteria
    E.5.1.1Timepoint(s) of evaluation of this end point
    Please see Appendix A of the protocol.
    E.5.2Secondary end point(s)
    Arm 1 (Low-Grade Glioma):
    -Type, frequency, and severity of AEs and laboratory abnormalities
    - Pharmacokinetic profile of DAY101 (e.g., area under the concentration-time curve [AUC], Cmin, etc.)
    - time following initiation of DAY101 to progression or death in patients treated with DAY101
    - length of response in patients with best overall confirmed response of CR or PR
    - time to first response following initiation of DAY101 in patients with best overall confirmed response of CR or PR

    Arm 2 (Low-Grade Glioma Extension):
    - Measured by the proportion of patients with best overall confirmed
    response of CR or PR as
    determined by the RANO criteria
    -Measured by the proportion of patients with best overall confirmed
    response of CR or PR by
    RAPNO–low-grade glioma criteria

    Arm 3 (Advanced Solid Tumor):
    -Type, frequency, and severity of AEs and laboratory abnormalities
    -Pharmacokinetic profile of DAY101 (e.g., AUC, Cmin, etc.)

    For the complete list of secondary endpoints please refer to the protocol
    E.5.2.1Timepoint(s) of evaluation of this end point
    Please see Appendix A of the protocol for further details.
    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 No
    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 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.8.3 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 EEA12
    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
    Switzerland
    Australia
    Canada
    Israel
    Korea, Republic of
    United Kingdom
    United States
    Germany
    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
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years4
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 140
    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) Yes
    F.1.1.4.1Number of subjects for this age range: 5
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 90
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 35
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 10
    F.1.3Elderly (>=65 years) No
    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 Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Young children not of age to provide consent. Parents/guardians may give consent on behalf of their children.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state4
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 40
    F.4.2.2In the whole clinical trial 140
    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
    G.4 Investigator Network to be involved in the Trial: 1
    G.4.1Name of Organisation Pacific Pediatric Neuro-Oncology Consortium (PNOC)
    G.4.3.4Network Country United States
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2021-03-09
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-04-16
    P. End of Trial
    P.End of Trial StatusRestarted
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