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    Summary
    EudraCT Number:2018-002250-79
    Sponsor's Protocol Code Number:CCR4938
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:GB - no longer in EU/EEA
    Date on which this record was first entered in the EudraCT database:2018-09-17
    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 number2018-002250-79
    A.3Full title of the trial
    iSCORE: Immunotherapy Sequencing in COlon and REctal Cancer.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    iSCORE: Immunotherapy Sequencing in COlon and REctal Cancer
    A.3.2Name or abbreviated title of the trial where available
    iSCORE
    A.4.1Sponsor's protocol code numberCCR4938
    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 SponsorThe Royal Marsden NHS Foundation Trust
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportBristol Myers Squibb
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationThe Royal Marsden NHS Foundation Trust
    B.5.2Functional name of contact pointGI & Lymphoma Clinical Trials Unit
    B.5.3 Address:
    B.5.3.1Street AddressDepartment of Medicine, The Royal Marsden NHS Foundation Trust
    B.5.3.2Town/ citySutton, Surrey
    B.5.3.3Post codeSM2 5PT
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number02086613807
    B.5.5Fax number02086613750
    B.5.6E-mailrichard.crux@rmh.nhs.uk
    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 Yes
    D.2.1.1.1Trade name nivolumab
    D.2.1.1.2Name of the Marketing Authorisation holderBristol Myers Squibb
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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 namenivolumab
    D.3.4Pharmaceutical form Solution for injection/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 INNnivolumab
    D.3.9.1CAS number 946414944
    D.3.9.2Current sponsor codebms marketing no
    D.3.9.3Other descriptive namenivolumab
    D.3.9.4EV Substance CodeAS1
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    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) Yes
    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 nameRelatlimab
    D.3.2Product code BMS-986016
    D.3.4Pharmaceutical form Solution for injection/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 INNrelatlimab
    D.3.9.2Current sponsor codeBMS-986016
    D.3.9.3Other descriptive nameanti-LAG3
    D.3.9.4EV Substance CodeAS2
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    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) Yes
    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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Metastatic RAS wild-type colorectal cancer which has previously responded to FOLFIRI chemotherapy and Cetuximab treatment but then progressed
    E.1.1.1Medical condition in easily understood language
    Advanced cancer of the colon or rectum which initially appeared to become smaller on treatment with FOLFIRI and Cetuximab treatment but now has either grown, reappeared or spread
    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
    The principle objective of the iSCORE study is to evaluate how effective Nivolumab and Relatlimab is at controlling colorectal cancer 6 months after starting treatment in patients with RAS/RAF wild type metastatic colorectal cancers who initially had a response to first line Cetuximab and FOLFIRI treament but then progressed. This will be determined on a type of radiological scan, called a CT or MRI scan, which will be performed every 8 weeks for the first year and every 12 weeks for the second year.
    E.2.2Secondary objectives of the trial
    The iSCORE study will also determine how safe and tolerable (how much any side effects can be sensibly tolerated) Nivolumab and Relatlimab treatment is for patients with colon and rectal cancers and to assess further efficacy measures including obejective radiological response rate, progression free survival and overall survival.

    We also have a number of exploratory objectives which aim to determine mechanisms of resistance to treatment and/or identify predictive or prognostic biomarkers to understand how combination immunotherapy can be further improved in this disease.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    • Male or female patients aged ≥18 years
    • Patients with histologically confirmed advanced/metastatic RAS/RAF wild type colon or rectal adenocarcinoma who had a prior radiological response to first line treatment with FOLFIRI and Cetuximab but have subsequently progressed/ become refractory to this treatment based on physician judgment
    • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
    • Estimated life expectancy of at least 3 months at the time of informed consent per Investigator assessment
    • Adequate organ functioning including haematological, renal, liver and cardiac function
    • Negative serum or urine pregnancy test at screening for women of childbearing potential and use of highly effective contraception for both male and female subjects throughout the study
    • Patient must consent and be eligible to undergo mandatory baseline and sequential biopsies
    • Presence of measurable disease as defined by RECIST v 1.1 criteria for response assessment
    E.4Principal exclusion criteria
    • Systemic therapy within 4 weeks prior to the planned administration of the first study treatment dose
    • Major surgery within 4 weeks or radiation therapy within 14 days prior to study entry. Prior palliative radiotherapy to metastatic lesion(s) is permitted, provided it has been completed 48 hours prior to study entry and there is at least one measurable lesion that has not been irradiated.

    • Previous exposure to immune checkpoint inhibitors or immune co-stimulatory drugs
    • Uncontrolled or significant cardiovascular disease including including patients with a history of myocarditis, regardless of aetiology
    • Known severe hypersensitivity reactions (Grade ≥ 3 NCI CTCAE v 5.0) to monoclonal antibodies or related compounds or any of their components
    • Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
    • Known history of testing positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
    • Positive test for HBV surface antigen and / or confirmatory HCV RNA (if anti-HCV antibody tested positive)
    • Active, known or suspected autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Subjects with type I diabetes mellitis, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
    • Patients with a history of interstitial lung disease or radiological evidence of pulmonary fibrosis
    • Pregnancy or lactation
    • Vaccination within 4 weeks of the first dose of study drugs and while on trial is prohibited except for administration of inactivated vaccines
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint of the study is the proportion of patients who remain radiologically progression free at 6 months from treatment initiation i.e. disease control control rate (DCR) at 6 months.
    E.5.1.1Timepoint(s) of evaluation of this end point
    6 months from treatment initiation
    E.5.2Secondary end point(s)
    • The safety and tolerability profile of Nivolumab and Relatlimab in patients with metastatic CRC according to the NCI CTCAE version 5.0 toxicity aggregate

    • Best Disease Control Rate (DCR), as defined above for the primary endpoint, at 12 months and 24 months from initiation of treatment

    • Duration of disease control defined as the time between the initial response (radiological SD/CR/PR using RECIST 1.1 criteria) to therapy and subsequent disease progression/ relapse or relapsedeath. Progressive disease (PD) here will include clinical progression as well in the absence of radiological evidence. The disease control rate will be defined as either SD/CR/PR using RECIST 1.1 and iRECIST criteria). PD will include clinical progression as well

    • Best Objective Response Rate (ORR) will be defined as either CR/PR (i.e. objective response using the RECIST 1.1 and iRECIST criteria). PD will include clinical progression as well. The timepoints of interest include 6 months, 12 months and 24 months from initiation of treatment

    • Progression Free Survival (PFS) defined as time from registration to progression (radiological or clinical) or death.

    • Overall Survival (OS) defined as time from registration to death.
    E.5.2.1Timepoint(s) of evaluation of this end point
    6 months, 12 months and 24 months from treatment initiation
    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 No
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    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 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.8.3 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 concerned1
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    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 study end date is deemed to be the date of last data capture. Patient follow up will continue until death to evaluate the survival endpoint of the trial.
    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.1.1Number of subjects for this age range: 0
    F.1.1.1In Utero No
    F.1.1.1.1Number of subjects for this age range: 0
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.2.1Number of subjects for this age range: 0
    F.1.1.3Newborns (0-27 days) No
    F.1.1.3.1Number of subjects for this age range: 0
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.4.1Number of subjects for this age range: 0
    F.1.1.5Children (2-11years) No
    F.1.1.5.1Number of subjects for this age range: 0
    F.1.1.6Adolescents (12-17 years) No
    F.1.1.6.1Number of subjects for this age range: 0
    F.1.2Adults (18-64 years) No
    F.1.2.1Number of subjects for this age range: 0
    F.1.3Elderly (>=65 years) No
    F.1.3.1Number of subjects for this age range: 0
    F.2 Gender
    F.2.1Female No
    F.2.2Male No
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    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 state25
    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)
    Trial participates will only be able to receive treatment with relatlimab and nivolumab for a maximum of 24 months as this is the maximum duration that has been funded for by BMS. If patients are still on nivolumab and relatlimab treatment approaching the end of this two year period, the trials team will discuss possible next treatment options with the patient.

    Patients will also continue to be followed up for 30, 60 and 100 days after their last dose of nivolumab and relatlimab treatment.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2018-10-30
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-11-29
    P. End of Trial
    P.End of Trial StatusGB - no longer in EU/EEA
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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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