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    Summary
    EudraCT Number:2017-002821-39
    Sponsor's Protocol Code Number:MCLA-128-CL02
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2019-04-15
    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 ConcernedNetherlands - Competent Authority
    A.2EudraCT number2017-002821-39
    A.3Full title of the trial
    Phase 2 study of MCLA-128-based combinations in metastatic breast cancer (MBC): MCLA-128/trastuzumab/chemotherapy in HER2-positive MBC and MCLA-128/endocrine therapy in estrogen receptor positive and low HER2 expression MBC
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Phase 2 study of MCLA-128-based combinations in metastatic breast cancer (MBC) : with endocrine therapy for patients with presenting high expression of hormone receptors or with trastuzumab/chemotherapy for patients presenting a high expression of a specific receptor (HER2)
    A.4.1Sponsor's protocol code numberMCLA-128-CL02
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT03321981
    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 SponsorMerus N.V.
    B.1.3.4CountryNetherlands
    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 supportMerus N.V.
    B.4.2CountryNetherlands
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationOncology Therapeutic Development
    B.5.2Functional name of contact pointMCLA-128-CL02 project manager
    B.5.3 Address:
    B.5.3.1Street Address100 rue Martre
    B.5.3.2Town/ cityClichy
    B.5.3.3Post code92110
    B.5.3.4CountryFrance
    B.5.4Telephone number33147150101
    B.5.6E-mailotd@oncotd.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 MCLA-128
    D.3.4Pharmaceutical form 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 assigned
    D.3.9.1CAS number Not assigned
    D.3.9.2Current sponsor codeMCLA-128
    D.3.9.3Other descriptive nameMCLA-128
    D.3.9.4EV Substance CodeSUB169257
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    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
    Metastatic Breast Cancer
    E.1.1.1Medical condition in easily understood language
    Metastatic Breast Cancer
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10027475
    E.1.2Term Metastatic breast 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
    Cohort 1 (HER2-positive/amplified MBC): MCLA-128 + trastuzumab ± vinorelbine:
    Evaluate efficacy of MCLA-128 combined with trastuzumab ± vinorelbine in terms of clinical benefit rate (CBR) at 24 weeks based on RECIST 1.1 (per investigator review) in HER2-positive/amplified MBC patients who have progressed on prior HER2-directed therapy that included trastuzumab, pertuzumab, and an HER2 antibody drug conjugate (ADC)

    Cohort 2 (estrogen receptor [ER]-positive/low HER2 expression MBC): MCLA-128 + endocrine therapy:
    Evaluate efficacy of MCLA-128 combined with endocrine therapy in terms of CBR at 24 weeks based on RECIST 1.1 (per investigator review) in ER-positive and low HER2 expression MBC patients who have previously progressed on the same endocrine therapy
    E.2.2Secondary objectives of the trial
    Cohort 1, evaluate:
    - CBR at 24 weeks (RECIST 1.1 per central review)
    - progression-free survival (PFS; per investigator/central review)
    - overall response rate (ORR) based on RECIST 1.1 (per investigator/central review).
    - duration of response (DoR) based on RECIST v1.1 (per investigator/central review)
    - overall survival (OS)
    - safety and tolerability of MCLA-128 in combination with trastuzumab ± vinorelbine
    - pharmacokinetics (PK) of MCLA-128 in combination with trastuzumab ± vinorelbine
    - immunogenicity of MCLA-128 in combination with trastuzumab

    Cohort 2, evaluate:
    - CBR at 24 weeks based on RECIST 1.1 per central review
    - PFS (per investigator/central review)
    - ORR based on RECIST 1.1 (per investigator/central review)
    - DoR based on RECIST 1.1 (per investigator/central review)
    - OS
    - safety and tolerability of MCLA-128 combined with endocrine therapy
    - PK of MCLA-128 combined with endocrine therapy
    - immunogenicity of MCLA-128 combined with endocrine therapy
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Signed informed consent before initiation of any study procedures.
    2. Women with histologically or cytologically confirmed breast cancer with evidence of metastatic or locally advanced disease not amenable to any local therapy with curative intent:
    2.1 Cohort 1 (MCLA-128 + trastuzumab ± vinorelbine)
    a. Documented HER2 overexpression/amplification, defined as immunohistochemistry (IHC) 3+ positive, or IHC 2+ combined with positive fluorescence in situ hybridization (FISH), based on local analysis on the most recent tumor biopsy (preferably metastatic, otherwise primary), either fresh or archival collected within 24 months before screening..
    b. Documented disease progression (by investigator assessment) on up to a maximum of 5 lines of HER2-directed therapy administered in the metastatic setting, and have progressed on the most recent line. Trastuzumab, pertuzumab and an HER2 antibody drug conjugate (e.g. T-DM1) must have been previously administered in any sequence and in any setting.
    2.2 Cohort 2 (MCLA-128 + endocrine therapy)
    a. Documented hormone receptor positive status (estrogen receptor positive [ER+] and/or progesterone receptor positive [PR+]), defined as ≥ 1% positive stained cells by local standards, based on local analysis on the most recent tumor biopsy
    b. Documented low-level HER2 expression, defined as IHC HER2 1+, or IHC HER2 2+ combined with negative FISH, based on local testing on a fresh tumor biopsy or an archival biopsy collected within 24 months before screening (preferably metastatic otherwise primary).
    c. No more than 3 lines of prior endocrine therapy (aromatase inhibitor or fulvestrant) for metastatic disease, with radiologically documented disease progression on the last line, after at least 12 weeks of therapy.
    d. Progression on a cyclin-dependent kinase inhibitor.
    e. No more than two previous chemotherapy regimen for advanced/metastatic disease.
    Note: Pre/peri-menopausal women can be enrolled if amenable to be treated with the LHRH agonist goserelin. Such patients must have commenced treatment with goserelin or an alternative LHRH agonist at least 4 weeks prior to study entry, and patients who received an alternative LHRH agonist prior to study entry must switch to goserelin for the duration of the trial.
    3. In Cohort 1, patients must have at least one lesion with measurable disease as defined by RECIST version 1.1. In Cohort 2, patients must have at least one lesion with measurable disease as defined by RECIST version 1.1. Patients with bone-only disease are eligible, even in the absence of measurable disease. Patients with bone-only disease must have lytic or mixed lesions (lytic + sclerotic). For Cohort 2, imaging documenting progression on the last line of hormone therapy must be available for central review..
    4. Age ≥ 18 years at signature of informed consent.
    5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
    6. Life expectancy of ≥ 12 weeks, as per investigator.
    7. Left ventricular ejection fraction (LVEF) ≥ 50% by echocardiogram (ECHO) or multiple gated acquisition scan (MUGA).
    8. Adequate organ function:
    a. Absolute neutrophil count (ANC) ≥ 1.5 X 109/L
    b. Hemoglobin ≥ 9 g/dL
    c. Platelets ≥ 100 x 109/L
    d. Serum calcium within normal ranges (or corrected with supplements)
    e. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal (ULN) and total bilirubin ≤ 1.5 x ULN (in cases of liver involvement, ALT/AST ≤ 5 x ULN and total bilirubin within normal ranges will be allowed)
    f. Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 60 mL/min calculated according to the Cockroft and Gault formula or MDRD formula for patients aged > 65 years (Appendix 19.2)
    g. Serum albumin > 3.0 g/dL
    E.4Principal exclusion criteria
    1. Central nervous system metastases that are untreated or symptomatic, or require radiation, surgery, or continued steroid therapy to control symptoms within 14 days of study entry.
    2. Known leptomeningeal involvement.
    3. Advanced/metastatic, symptomatic, visceral spread, with a risk of life-threatening complications in the short term (including patients with massive uncontrolled effusions [pleural, pericardial, peritoneal], pulmonary lymphangitis, and over 50% liver involvement).
    4. Participation in another interventional clinical trial or treatment with any investigational drug within 4 weeks prior to study entry.
    5. Any systemic anticancer therapy within 3 weeks of the first dose of study treatment. For cytotoxic agents that have major delayed toxicity, e.g. mitomycin C and nitrosoureas, or anticancer immunotherapies, a washout period of 6 weeks is required. For patients in Cohort 2, this does not apply to the most recently received hormone therapy.
    6. Major surgery or radiotherapy within 3 weeks of the first dose of study treatment. Patients who received prior radiotherapy to ≥ 25% of bone marrow are not eligible, irrespective of when it was received.
    7. Persistent grade > 1 clinically significant toxicities related to prior antineoplastic therapies (except for alopecia); stable sensory neuropathy ≤ grade 1 NCI-CTCAE v. 4.0 is allowed.
    8. History of hypersensitivity reaction or any toxicity attributed to trastuzumab, murine proteins or any of the excipients that warranted permanent cessation of these agents (applicable for Cohort 1 only).
    9. Previous exposure to vinorelbine (applicable for Cohort 1 triplet combination only)
    10. Exposure to the following cumulative anthracycline doses:
    a. Doxorubicin or liposomal doxorubicin > 360 mg/m²
    b. Epirubicin > 720 mg/m²
    c. Mitoxantrone > 120 mg/m² and idarubicin > 90 mg/m²
    d. Other anthracycline at a dose equivalent to > 360 mg/m² doxorubicin
    e. For patients having received > 1 anthracycline, the cumulative dose must not exceed the equivalent of 360 mg/m² doxorubicin
    11. Chronic use of high-dose oral corticosteroid therapy (>10 mg of prednisone equivalent a day).
    12. Uncontrolled hypertension (systolic > 150 mmHg and/or diastolic > 100 mmHg) or unstable angina.
    13. History of congestive heart failure of Class II-IV New York Heart Association (NYHA) criteria, or serious cardiac arrhythmia requiring treatment (except atrial fibrillation, paroxysmal supraventricular tachycardia).
    14. History of myocardial infarction within 6 months of study entry.
    15. History of prior or concomitant malignancies (other than excised non-melanoma skin cancer or cured in situ cervical carcinoma) within 3 years of study entry.
    16. Current dyspnea at rest of any origin, or other diseases requiring continuous oxygen therapy.
    17. Current serious illness or medical conditions including, but not limited to uncontrolled active infection, clinically significant pulmonary, metabolic or psychiatric disorders.
    18. Known HIV, HBV, or HCV infection.
    19. Pregnant or lactating women; women of childbearing potential must use effective contraception methods (patient and/or partner, e.g., surgical sterilization, a reliable barrier method) prior to study entry, for the duration of study participation, and for 7 months after the last dose of MCLA-128/trastuzumab. See Section 8.10.
    20. Patients with only non-measurable lesions other than bone metastasis (e.g. pleural effusion, ascites or other visceral locations).
    21. Patients with bone-only disease with blastic-only metastasis.
    E.5 End points
    E.5.1Primary end point(s)
    Cohorts 1 and 2: CBR per investigator radiologic review at 24 weeks
    E.5.1.1Timepoint(s) of evaluation of this end point
    Tumor assessment 24 weeks after treatment start
    E.5.2Secondary end point(s)
    Cohort 1: CBR at 24 weeks per central review, and ORR, PFS, and DoR per investigator and central review

    Cohort 2: CBR at 24 weeks per central review, and PFS per investigator and central review
    E.5.2.1Timepoint(s) of evaluation of this end point
    CBR and ORR per central review: tumor assessment at 24 weeks
    PFS and DoR: at patient's disease progression
    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 Yes
    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 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) Information not present in EudraCT
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA22
    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
    United States
    Belgium
    France
    Netherlands
    Portugal
    Spain
    United Kingdom
    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 years3
    E.8.9.1In the Member State concerned months3
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years4
    E.8.9.2In all countries concerned by the trial months10
    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: 45
    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 No
    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 state70
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 90
    F.4.2.2In the whole clinical trial 120
    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)
    Follow up:
    - for safety for 30 days, then until resolution of any related AEs, LVEF every 6 months for 1 year after last dose
    - every 3 months, pts who discontinue:
    - for reasons other than PD will be followed-up for tumor assessments , disease progression, new anticancer therapy, or 1 year
    - due to a drop in LVEF: MUGA/ultrasound every 3 months until initiation of a new anticancer therapy, resolution of LVEF to > 50%
    - for survival, related cardiac events ,related SAEs: up to 1 year.
    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 Decision2019-04-15
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-06-28
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2023-07-26
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