Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43876   clinical trials with a EudraCT protocol, of which   7294   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2020-000630-17
    Sponsor's Protocol Code Number:MER-XMT-1536-1
    National Competent Authority:Bulgarian Drug Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2021-06-25
    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 ConcernedBulgarian Drug Agency
    A.2EudraCT number2020-000630-17
    A.3Full title of the trial
    A Phase 1b/2, First-in-Human, Dose Escalation and Expansion Study of XMT-1536 In Patients with Solid Tumors Likely to Express NaPi2b
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A dose escalation and expansion study of XMT-1536 en patients with solid tumors.
    A.4.1Sponsor's protocol code numberMER-XMT-1536-1
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT03319628
    A.5.4Other Identifiers
    Name:IND numberNumber:135,571
    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 SponsorMersana Therapeutics, 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 supportMersana Therapeutics, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMersana Therapeutics, Inc.
    B.5.2Functional name of contact pointClinical Operations
    B.5.3 Address:
    B.5.3.1Street Address840 Memorial Drive
    B.5.3.2Town/ cityCambridge, Massachusetts
    B.5.3.3Post code02139
    B.5.3.4CountryUnited States
    B.5.6E-mailXMT-1536-Clinical@mersana.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.3.1Product nameUpifitamab rilsodotin
    D.3.2Product code XMT-1536
    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 INNUpifitamab Rilsodotin
    D.3.9.1CAS number 2254119-00-9
    D.3.9.2Current sponsor codeXMT-1536
    D.3.9.3Other descriptive nameXMT-1536
    D.3.9.4EV Substance CodeSUB193958
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number80
    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
    High grade serous ovarian cancer or non-small cell lung cancer (NSCLC), adenocarcinoma subtype
    E.1.1.1Medical condition in easily understood language
    Ovarian cancer or non-small cell lung 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 PT
    E.1.2Classification code 10033128
    E.1.2Term Ovarian cancer
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10061873
    E.1.2Term Non-small cell lung cancer
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Primary in Dose Escalation (DES):
    Determine the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of XMT-1536 administered intravenously once every 28 days
    Assess the safety and tolerability of XMT-1536

    Primary in Expansion (EXP):
    Assess further safety and tolerability using the MTD or RP2D identified in DES
    Assess the preliminary anti-neoplastic activity of XMT-1536

    Primary in Pivotal Cohort (UPLIFT):
     Determine the confirmed investigator-assessed objective response rate of XMT-1536 (upifitamab rilsodotin) at a starting dose level of 36
    mg/m2 q4wk capped at 2.2 m2 in patients with higher (TPS≥75) sodium-dependent phosphate transport protein 2b (NaPi2b) expressing platinum-resistant high-grade serous ovarian cancer (HGSOC), including cancers of ovarian, fallopian tube or primary peritoneal origin)
    E.2.2Secondary objectives of the trial
    Secondary in DES:
    Assess preliminary anti-neoplastic activity of XMT-1536
    Secondary in DES and EXP:
    Assess PK, release product, selected metabolites, development of anti-drug antibodies and association of tumor expression of NaPi2b and objective tumor response to XMT-1536
    Assess safety and efficacy in ovarian cancer subpopulations, including patients previously treated and failed therapy with bevacizumab and patients with and without Breast Cancer type 1 susceptibility gene (BRCA) mutation who were previously treated and failed therapy with poly ADP ribose polymerase inhibitors (PARPi).

    Secondary in UPLIFT:
     Assess confirmed investigator-assessed objective response rate of XMT-1536 regardless of NaPi2b expression.
     Assess confirmed objective response rate by indep radiology review (IRR) for patients with high (TPS≥75) NaPi2b and overall.
     Assess duration of objective response (DOR) in patients who achieve a response.
     Assess incidence and severity of adverse events.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    For Dose Escalation, Expansion and Uplift
    1. Females and males, aged ≥18 years old
    2. ECOG performance status 0 or 1
    3. Measurable disease as per RECIST, version 1.1
    4. Resolution of all acute toxic effects of prior therapy or surgical procedures to ≤Grade 1 (except alopecia, stable immune-related toxicity such as hypothyroidism on hormone replacement, adrenal insufficiency on ≤10 mg daily [prednisone] (or equivalent), chronic Grade 2 peripheral sensory neuropathy after prior taxane therapy).
    5. Cardiac left ventricular ejection fraction (LVEF) ≥50% or ≥ the institution’s lower limit of normal by either Echo or MUGA scan
    6. Adequate organ function as defined by the following criteria:
    a. Absolute neutrophil count (ANC) ≥1500 cells/mm3
    b. Platelet count ≥100,000/mm3
    c. Hemoglobin ≥9 g/dLa
    d. In patients not on anticoagulation therapy: INR, activated partial thromboplastin time (aPTT), and prothrombin time (PT) all within 1.2 times the institutional upper limit of normal (ULN) in the absence of any other indicator of liver dysfunction. Patients on anticoagulants are allowed if their relevant laboratory values are within the therapeutic window.
    e. Estimated glomerular filtration rate (GFR) ≥45 mL/min
    f. Total bilirubin ≤ULN
    Patients with asymptomatic elevations in unconjugated bilirubin due to Gilbert syndrome or stable chronic hemolytic anemia may be eligible after discussion with the Sponsor Medical Monitor.
    7. Aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT) ≤1.5 times the institutional ULN.
    8. Albumin ≥3.0 g/dL
    9. Female participants of child-bearing potential must use a highly effective non-hormonal form of contraception for the duration of study drug administration and for at least 6 months after the last dose of study drug.
    Please see Appendix 7 of the Protocol for examples of non-hormonal highly effective contraceptive methods.
    10. Male study participants must use barrier contraception (condoms) for the duration of study drug and for at least 6 months after the last dose of study drug. The WOCBP partners of male study participants must use highly effective contraception for the duration of study drug and for at least 6 months after the last dose of study drug
    10. Able to provide informed consent



    E.4Principal exclusion criteria
    For Dose Escalation, Expansion and Uplift
    1. Major surgery within 28 days of starting study treatment, systemic anti-cancer therapy within the lesser of 28 days or 5 half-lives of the prior therapy before starting study treatment (14 days or 5 half-lives for small molecule targeted therapy), or recent radiation therapy with unresolved toxicity or within a time window of potential toxicity (consultation with the Sponsor Medical Monitor is recommended).
    2. Patients with untreated CNS metastases (including new and progressive brain metastases), history of leptomeningeal metastasis or carcinomatous meningitis.
    a. Patients are eligible if CNS metastases are adequately treated and patients are neurologically stable for at least 2 weeks prior to enrollment.
    b. In addition, patients must be either off corticosteroids, or on a stable/decreasing dose of ≤ 10 mg daily prednisone (or equivalent). Anticonvulsants are allowed except for those drugs associated with liver toxicity.
    3. Untreated known human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV). In addition, negative serology is required during screening (baseline) for HBV and HCV:
    a. HBV: Patients with serologic evidence of chronic HBV infection should have an HBV viral load below the limit of quantification to be eligible.
    b. HCV: Patients with a history of HCV infection should have completed curative antiviral treatment and HCV viral load below the limit of quantification.
    c. HIV: screening for HIV is not required except if mandated by local regulations or indicated based on clinical assessment.
    4. Current severe, uncontrolled systemic disease (e.g., clinically
    significant cardiovascular, pulmonary, or metabolic disease) or
    intercurrent illness that could risk of adverse events, whether or not
    potentially related to study treatment (in unclear cases, consultation
    with the Medical Monitor is recommended). Further, patients are
    excluded with the following characteristics:
    a. A marked baseline prolongation of QT/QTc interval using Frederica's QT correction formula.
    b. A history of additional risk factors for Torsade's de Pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome).
    c. The use of concomitant medications that prolong the QT/QTc interval will be reviewed first with the Sponsor Medical Monitor.
    5. History of cirrhosis, hepatic fibrosis, esophageal or gastric varices, or other clinically significant liver disease. FibroScan testing may be
    required for patients with a history of chronic liver disease, e.g., fatty
    liver. Testing beyond laboratory studies otherwise defined in the
    eligibility criteria, to diagnose potentially clinically significant liver
    disease based on risk factors such as hepatic steatosis or history of
    excessive alcohol intake, will be based on clinical judgement of the
    investigator.
    6. Patients cannot receive drugs associated with hepatotoxicity concurrent with XMT-1536 administration. Patients may receive acetaminophen/paracetamol for a limited time but at a total daily dose of ≤2 g per day. Use of NSAIDs or steroids for treatment of fever is encouraged.
    7. Current use of either constant or intermittent supplementary oxygen therapy.
    8. History of or suspected pneumonitis, or interstitial lung disease
    9. Oxygen saturation on room air <93%.
    10. Pregnant or nursing women
    11.Diagnosis of additional malignancy that progressed or required
    active treatment within at least 2 years , except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix
    12. Active corneal disease, or history of corneal disease within 12
    months prior to enrollment.
    13. Use of strong CYP450 3A inhibitors or inducers that cannot be discontinued while receiving study treatment.
    14.Known sensitivity to any of the study medications, or components
    thereof, or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation
    15.In the Czech Republic, patients cannot be enrolled if they have
    received a live/attenuated vaccine within 30 days of study entry or if
    they plan to receive a live/attenuated vaccine while on treatment
    through 90 days post the last dose of study medication
    E.5 End points
    E.5.1Primary end point(s)
    For dose escalation:
    - Maximum Tolerated Dose (MTD)
    - Recommended Phase 2 dose (RP2D)
    - Safety and Tolerability Measures
    For dose expansion
    - Safety and Tolerability Measures
    - Objective Response Rate (ORR)
    - Disease Control Rate (DCR)
    For UPLIFT:
    Objective Response Rate (ORR) in the ITT-Higher NaPi2b population
    E.5.1.1Timepoint(s) of evaluation of this end point
    For dose escalation:
    MTD: assessed once at the end of dose escalation.
    RP2D: assessed once at the end of dose escalation.
    Safety and Tolerability Measures: evaluated at every patient visit.
    For dose expansion:
    Safety and Tolerability Measures: evaluated at every patient visit.
    ORR: measured once at the end of study using a composite of RECIST evaluations that are compared to each patient’s baseline measurement and subsequent post exposure to XMT-1536.
    DCR: determined once at the end of the study by adding CR+PR+SD based on the best overall response for the study.
    For UPLIFT:
    - measured once at the end of study using a composite of RECIST
    evaluations that are compared to each patient's baseline measurement and subsequent post exposure to XMT-1536.
    E.5.2Secondary end point(s)
    For dose escalation:
    Objective response rate (ORR)
    Duration of response (DOR)
    Disease control rate (DCR) = CR + PR + SD (any duration)
    PK profile of XMT-1536, its release product, and metabolites
    Anti-drug antibody levels and nAb levels
    NaPi2b protein or RNA levels measured in tumor samples

    For dose expansion:
    PK profile of XMT-1536, its release product, and metabolites
    Anti-drug antibody levels and nAb levels NaPi2b protein or RNA levels measured in tumor samples
    Analyze the effect of NaPi2b expression on objective response
    DOR, PFS, OS
    Sub-group analyses of responses in ovarian cancer patients including patients
    previously treated and failed therapy with bevacizumab and patients with and without BRCA mutation who were previously treated and failed therapy with PARP inhibitors.

    Uplift:
    Confirmed investigator-assessed ORR in the entire ITT population
    ORR by IRR in the ITT-Higher NaPi2b population; ORR by IRR in the entire ITT population
    DOR in the ITT-Higher NaPi2b population
    DOR in the entire ITT population
    Safety and tolerability measures
    E.5.2.1Timepoint(s) of evaluation of this end point
    For dose escalation:
    - ORR: see E.5.1.1
    - DCR: see E.5.1.1
    For dose expansion:
    - DOR, PFS, OS: end of study/patient last contact with site
    - Sub-group analyses of responses: end of study
    - NaPi2b expression: tumor samples collected at study entry and no later than 20 days after first dose

    For dose escalation & expansion:
    - ADA & nAB: Samples collected pre-first dose during Screen, pre-dose in Cycles 2, 3, 4 and all even number cycles after. ADA positive samples to be tested for nAB
    - NaPi2b protein or RNA levels: Biopsies obtained prior to first dose and at end of treatment
    - PK: Cycle 1 & 3: PK samples collected at Cycle 1 pre-dose, EOI, EOI+4, EOI+6, and at each visit after. Cycles 2, 4 and subsequent cycles: PK samples collected pre-dose, EOI and at each visit after
    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.8.3 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 concerned6
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA80
    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
    New Zealand
    Australia
    Belgium
    Bulgaria
    Canada
    Denmark
    Estonia
    Finland
    France
    Italy
    Lithuania
    Norway
    Poland
    Spain
    Sweden
    United Kingdom
    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
    Subjects will have an End of Treatment Visit (LSLV) and thereafter will be followed for survival via telephone calls every 3 months.
    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 months5
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years5
    E.8.9.2In all countries concerned by the trial months4
    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: 211
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 211
    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 state24
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 100
    F.4.2.2In the whole clinical trial 422
    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)
    The primary reason for discontinuation from the study is disease progression. At that time, all subsequent treatment will come from a patient’s primary oncologist.
    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 Decision2021-09-20
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-08-31
    P. End of Trial
    P.End of Trial StatusCompleted
    For support, Contact us.
    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.

    European Medicines Agency © 1995-Sun May 12 16:54:58 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA