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    Summary
    EudraCT Number:2019-004418-32
    Sponsor's Protocol Code Number:U31402-A-U202
    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:2020-06-26
    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 ConcernedUK - MHRA
    A.2EudraCT number2019-004418-32
    A.3Full title of the trial
    A MULTI-CENTER, OPEN-LABEL, PHASE 2 STUDY TO EVALUATE SAFETY AND EFFICACY OF U3-1402 IN SUBJECTS WITH ADVANCED OR METASTATIC COLORECTAL CANCER (CRC)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study of U3-1402 in subjects with colorectal cancer
    A.4.1Sponsor's protocol code numberU31402-A-U202
    A.5.4Other Identifiers
    Name:IND numberNumber:148299
    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 SponsorDAIICHI SANKYO, INC
    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 supportDAIICHI SANKYO, INC
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationSyneos Health LLC
    B.5.2Functional name of contact pointLisa Ochsner
    B.5.3 Address:
    B.5.3.1Street Address1030 Sync Street
    B.5.3.2Town/ cityMorrisville
    B.5.3.3Post codeNC 27560
    B.5.3.4CountryUnited States
    B.5.4Telephone number+1919876 9300
    B.5.5Fax number+1919876 9360
    B.5.6E-mailLisa.Ochsner@syneoshealth.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 U3-1402
    D.3.4Pharmaceutical form Powder 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 INNPatritumab deruxtecan
    D.3.9.1CAS number N/A
    D.3.9.2Current sponsor codeU3-1402
    D.3.9.3Other descriptive nameN/A
    D.3.9.4EV Substance CodeSUB204104
    D.3.10 Strength
    D.3.10.1Concentration unit mg/g milligram(s)/gram
    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 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
    Advanced or metastatic colorectal cancer (CRC) which is resistant, refractory, or intolerant to at least 2 prior lines of therapy, that must include all of the following agents: fluoropyrimidine, irinotecan, platinum agent, an anti-epidermal growth factor receptor (EGFR) agent (if clinically indicated), an anti-vascular endothelial growth factor (VEGF) agent (if clinically indicated), an immune checkpoint inhibitor (if clinically indicated), and a BRAF inhibitor (if clinically indicated).
    E.1.1.1Medical condition in easily understood language
    Advanced or metastatic colorectal cancer, which is resistant and refractory to at least 2 prior lines of therapy
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level LLT
    E.1.2Classification code 10052362
    E.1.2Term Metastatic colorectal cancer
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To assess the tolerability and antitumor activity of U3-1402 in subjects with advanced or metastatic CRC who are resistant, refractory, or intolerant to at least 2 prior lines of therapy
    E.2.2Secondary objectives of the trial
    To investigate the durability of U3-1402 antitumor activity in subjects with advanced or metastatic CRC
    To further investigate the antitumor activity of U3-1402 in subjects with advanced or metastatic CRC
    To evaluate the safety and tolerability of U3 1402 in subjects with advanced or metastatic CRC
    To evaluate HER3 protein expression in tumor tissue and its relationship with efficacy
    To assess the immunogenicity incidence against U3-1402
    To characterize the 3 PK analytes of U3-1402 in subjects with advanced or metastatic CRC
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Subjects must satisfy all of the following criteria to be included in the study:
    1. Subject has provided written informed consent prior to the start of
    any study-specific procedures.
    2. Subjects ≥18 years (follow local regulatory requirements if the legal age of consent for study participation is >18 years old).
    3. Pathological/histological confirmation of advanced or metastatic colon or rectal adenocarcinoma.
    4. Must be resistant, refractory, or intolerant to at least 2 prior lines of systemic therapy, that must include all of the following agents:
    a. Fluoropyrimidine
    b. Irinotecan
    c. Platinum agents (eg, oxaliplatin)
    d. An anti-EGFR agent, if clinically indicated (eg, RAS/BRAF wildtype)
    e. An anti-VEGF agent, unless contraindicated (eg, bevacizumab)
    f. An immune checkpoint inhibitor, if clinically indicated (eg,
    microsatellite instability-high [MSI-H] status)
    g. A BRAF inhibitor, if clinically indicated (eg, BRAF V600E positive)
    5. Has at least 1 measurable lesion confirmed by blinded independent central review (BICR) as per (RECIST) Version (v) 1.1.
    6. Willing to provide a required pre-treatment tumor biopsy and an
    additional archival tissue sample for the assessment of HER3 expression levels by IHC and exploratory biomarkers, defined as:
    a. Pre-treatment tumor biopsy. Subjects may be exempted from the requirement to provide a pre-treatment tumor biopsy if archival tumor tissue was collected within 3 months of screening during or after treatment with the last prior cancer treatment and is of sufficient quantity (2 cores or 20 slides with adequate tumor tissue content).
    b. An additional archival tissue sample collected greater than 3 months prior to screening must be available and of sufficient quantity, as defined above, at the time of screening. If an archival tissue sample (collected greater than 3 months prior to screening) is not available, a subject may be included provided the pre-treatment tumor biopsy is obtained and after discussion and agreement from Sponsor (Medical Monitor or designee).
    c. Consent to provide on-treatment tumor biopsy. When at least 10 on-treatment tumor biopsies per cohort have been collected, the Sponsor will provide written notification of a change to the requirement.
    7. Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.
    8. Life expectancy ≥3 months.
    9. Has adequate bone marrow reserve and organ function at baseline based on local laboratory data, defined as within 14 days prior to Cycle 1 Day 1
    E.4Principal exclusion criteria
    Subjects who meet any of the following criteria will be denied entry to the study:
    1. Any history of interstitial lung disease (including pulmonary fibrosis or radiation pneumonitis), has current interstitial lung disease (ILD), or is suspected to have such disease by imaging during screening.
    2. Clinically severe pulmonary compromise (based on Investigator’s assessment) resulting from intercurrent pulmonary illnesses including, but not limited to:
    a. any underlying pulmonary disorder (eg, pulmonary emboli, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion)
    b. any autoimmune, connective tissue or inflammatory disorder with pulmonary involvement (eg, rheumatoid arthritis, Sjögren's syndrome, sarcoidosis)
    OR prior complete pneumonectomy.
    3. Is receiving chronic systemic corticosteroids dosed at >10 mg prednisone or equivalent anti-inflammatory activity or any form of immunosuppressive therapy prior to Cycle 1 Day 1. Subjects who require use of bronchodilators, inhaled or topical steroids, or local steroid injections may be included in the study.
    4. Evidence of leptomeningeal disease
    5. Evidence of clinically active spinal cord compression or brain metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Subjects with clinically inactive or treated brain metastases who are
    asymptomatic (ie, without neurologic signs or symptoms and do not
    require treatment with corticosteroids or anticonvulsants) may be
    included in the study. Subjects must have a stable neurologic status for
    at least 2 weeks prior to Cycle 1 Day 1.
    6. Inadequate washout period prior to Cycle 1 Day 1 of U3-1402:
    a. Whole brain radiation therapy <14 days or stereotactic brain radiation therapy <7 days;
    b. Any cytotoxic chemotherapy, investigational agent or other anticancer drug(s) from a previous cancer treatment regimen or clinical study <14 days or 5 half-lives, whichever is longer;
    c. Monoclonal antibodies other than immune checkpoint inhibitors, such
    as bevacizumab (anti-VEGF) and cetuximab (anti-EGFRs) <28 days;
    d. Immune checkpoint inhibitor therapy <21 days;
    e. Major surgery (excluding placement of vascular access) <4 weeks;
    f. Radiotherapy treatment to >30% of the bone marrow or with a wide field of radiation <28 days or palliative radiation therapy <14 days;
    g. Chloroquine or hydroxychloroquine <14 days.
    7. Prior treatment with an anti-HER3 antibody and/or antibody drug conjugate (ADC) that consists of an exatecan derivative that is any topoisomerase I inhibitor (eg, trastuzumab deruxtecan).
    8. Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 Grade ≤1 or baseline.
    9. Had primary malignancies other than CRC within 3 years, except adequately resected non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated.
    10. Uncontrolled or significant cardiovascular disease prior to Cycle 1 Day 1, including:
    a. QT interval corrected for heart rate using Fridericia’s formula prolongation interval of >470 (ms) for females and >450 ms for males within 28 days;
    b. Left ventricular ejection fraction (LVEF) <50% by either echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan within 28 days;
    c. Resting systolic blood pressure >180 mmHg or diastolic blood
    pressure >110 mmHg;
    d. Myocardial infarction within 6 months;
    e. New York Heart Association (NYHA) Classes 2 to 4 congestive heart failure (See Section 13.5) within 28 days;
    f. Uncontrolled angina pectoris within 6 months;
    g. Cardiac arrhythmia requiring antiarrhythmic treatment within 28 days.
    11. Active Hepatitis B and/or hepatitis C infection, such as those with serologic evidence of viral infection within 28 days of Cycle 1 Day 1.
    a. Subjects with past or resolved hepatitis B virus (HBV) infection are eligible if they met specific criteria (details listed in protocol)
    b. Subjects with a history of hep C infection will be eligible for enrolment only if the viral load according to local standards of detection is documented to be below the level of detection in the absence of anti-viral therapy during the previous 12 weeks (ie. sustained viral response according to the local product label but no less than 12 weeks, whichever is longer).
    E.5 End points
    E.5.1Primary end point(s)
    Objective Response Rate (ORR) is defined as the proportion of subjects with a best overall response (BOR) of confirmed complete response (CR) or partial response (PR).
    E.5.1.1Timepoint(s) of evaluation of this end point
    Data are collected at baseline, then from the start of study treatment until disease progression or by BICR, death, lost to follow-up, or
    withdrawal of consent by the subject.
    E.5.2Secondary end point(s)
    Duration of Response (DoR) is defined as the time from the first documented response (complete response [CR] or partial response [PR]) to the date of disease progression or death due to any cause.
    Objective Response Rate (ORR) is defined as the proportion of subjects with a best overall response (BOR) of confirmed CR or PR.
    Duration of Response (DoR) is defined as the duration from the first documented response to the date of disease progression or death due to any cause.
    Disease Control Rate (DCR) is defined as the proportion of subjects who achieved a confirmed BOR of CR, PR, or stable disease (SD).
    Time to Tumor Response (TTR) is defined as the time from the start of study treatment to the date of the first documentation of objective response (CR or PR) that is subsequently confirmed.
    Progression-Free Survival (PFS) is defined as the duration from the start of study treatment to the date of the first documentation of objective progressive disease (PD) or death due to any cause, whichever is earlier.
    Overall Survival (OS) is defined as the time from the start of study treatment to the date of death due to any cause.
    Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), adverse event of special interests (AESIs) (ILD and elevation of aminotransferases and TBL), ECOG PS, vital sign measurements, standard clinical laboratory parameters. AEs will be coded using the most recent version of MedDRA and will be graded using NCI-CTCAE v5.0.
    HER3 protein expression in tumor tissue (as determined by IHC) and correlation with efficacy
    Anti-drug Antibody (ADA) prevalence: The proportion of all subjects
    having a confirmed positive ADA sample at any point in time.
    ADA incidence: The proportion of subjects having treatment-emergent
    ADA. ADA titer will be determined for confirmed ADA-positive samples.
    Neutralizing antibodies: When neutralizing assay becomes available,
    confirmed ADA-positive samples may be analyzed for neutralizing
    activity.
    PK endpoints: Cmax, Tmax, Ctrough, AUClast, and AUCtau
    E.5.2.1Timepoint(s) of evaluation of this end point
    Data are collected at baseline, then from the start of study treatment until disease progression or by BICR, death, lost to follow-up, or
    withdrawal of consent by the subject.
    Death date is collected until the subject discontinues the study.
    HER3 data are collected at baseline (archival and pre-treatment tumor
    biopsy) and at Cycle 2.
    ADA prevalence, incidence, and titer for U3 1402 related data are
    collected from the start of study treatment until the end of treatment.
    Additional timepoints are specified in the protocol.
    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 Yes
    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 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 EEA14
    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
    Japan
    United States
    Belgium
    France
    Italy
    Poland
    Spain
    United Kingdom
    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
    LVLS
    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 months9
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months3
    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: 72
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 8
    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 state3
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 24
    F.4.2.2In the whole clinical trial 80
    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 time of study closure, any subjects who are continuing treatment with U3-1402 and who are judged by the Investigator to have ongoing benefit may continue to receive treatment with U3-1402 through a rollover protocol or another mechanism consistent with local requirements.
    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 Decision2020-08-10
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-10-30
    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
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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