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    Summary
    EudraCT Number:2017-000625-12
    Sponsor's Protocol Code Number:CTMX-M-2009-001
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2017-07-12
    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 ConcernedNetherlands - Competent Authority
    A.2EudraCT number2017-000625-12
    A.3Full title of the trial
    A Phase 1-2, Open-Label, Dose-Finding, Proof of Concept, First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of CX-2009 in Adults with Metastatic or Locally Advanced Unresectable Solid Tumors (PROCLAIM-CX-2009)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Open label, First in human study for CX-2009 in adults with metastatic or locally advanced unresectable solid tumors
    A.3.2Name or abbreviated title of the trial where available
    PROCLAIM-CX-2009
    A.4.1Sponsor's protocol code numberCTMX-M-2009-001
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT03149549
    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 SponsorCytomX 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 supportCytomX Therapeutics, Inc
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationCytomX Therapeutics, Inc
    B.5.2Functional name of contact pointClinical Trial Team
    B.5.3 Address:
    B.5.3.1Street Address151 Oyster Point Boulevard, Suite 400
    B.5.3.2Town/ citySouth San Francisco
    B.5.3.3Post codeCA 94080
    B.5.3.4CountryUnited States
    B.5.4Telephone number001650763-9501
    B.5.5Fax number001650515-3185
    B.5.6E-mailclinicaltrials@cytomx.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 nameCX-2009
    D.3.2Product code CX-2009
    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 INNNot established
    D.3.9.2Current sponsor codeCX-2009
    D.3.9.3Other descriptive nameCX-2009
    D.3.9.4EV Substance CodeSUB186901
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    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) 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 Yes
    D.3.11.13.1Other medicinal product typeProbody Drug Conjugate
    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 name89Zr-CX-2009
    D.3.2Product code 89Zr-CX-2009
    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 INN-
    D.3.9.2Current sponsor code89ZR-CX-2009
    D.3.9.3Other descriptive name89ZR-CX-2009
    D.3.9.4EV Substance CodeSUB191933
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number0.5
    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 Yes
    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 Yes
    D.3.11.13.1Other medicinal product typeprobody drug conjugate
    D.IMP: 3
    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 nameCX-072
    D.3.2Product code CX-072
    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 codeCX-072
    D.3.9.3Other descriptive nameCX-072
    D.3.9.4EV Substance CodeSUB184393
    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) 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 or locally advanced unresectable solid tumors in following
    indications: breast cancer (BC), castrate-resistant prostate
    carcinoma (CRPC), non-small cell lung carcinoma (NSCLC), ovarian epithelial
    cancer (EOC), endometrial carcinoma (EC), head and neck squamous
    cell carcinoma (HNSCC), or cholangiocellular carcinoma (CCC)
    E.1.1.1Medical condition in easily understood language
    Cancer
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10065147
    E.1.2Term Malignant solid tumor
    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
    PartA determine safety of CX2009, MTD/RP2D/DLTs of CX2009 given IV
    every 21d as monotherapy to pts with solid tumors.
    PartA2:characterize protease activity+measure cleavage of CX2009 in
    biopsies,blood in pts with high CD166 by IHC, obtain characterization of
    safety of CX2009 given as monotherapy.
    PartB:evaluate efficacy of CX2009 given IV every 21d as monotherapy at
    MTD/RP2D in pts with solid tumors (high CD166 by IHC).
    PartC1:determine safety of CX2009,MTD/RP2D/DLTs of CX2009 given IV
    every 14d as monotherapy to pts with solid tumors (high CD166 by IHC)
    PartC2:evaluate clinical activity of CX2009 given IV every 14d as
    monotherapy at MTD/RP2D to pts in an indication specific cohort high
    CD166 by IHC.
    Part D1:determine safety,MTD/RP2D/DLT's of CX2009 in comb with
    CX072 both given IV every 14d
    Part D2 evaluate efficacy of CX2009 in comb. with CX072 given IV every
    14d at MTD/R2PD to subjects PDL1+ and high CD166 by IHC.
    E.2.2Secondary objectives of the trial
    Evaluate preliminary efficacy in subjects treated with CX-2009 as monotherapy;
    Characterize the pharmacokinetics (PK) of CX-2009;
    Assess the incidence of anti-drug antibody (ADA) formation to CX-2009;
    Obtain additional characterization of the safety of CX-2009 at the MTD/RP2D;
    Evaluate efficacy in subjects treated with CX-2009 as monotherapy.
    Evaluate preliminary efficacy in subjects treated with CX-2009 and CX-072
    Characterize PK of CX-2009 when administered in combination with CX-072
    Assess incidence of ADA formation to CX-2009 when it's administered in
    combination with CX-072
    Characterize the PK profile of CX-072 when it's administered in
    combination with CX-2009
    Assess the incidence to ADA formation to CX-072 when it's administered
    with CX-2009
    Obtain additional characterization of safety of CX-2009 when
    administered with CX-072 at MTD/RP2D
    Evaluate Efficacy of CX-2009 + CX072
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Substudy protocol title: 89Zr-CX-2009 PET Imaging in Subjects with Unresectable Locally Advanced or Metastatic Solid Tumors

    Protocol Module Number: PROCLAIM CTMX-M-2009-001 substudy

    The primary objective of the substudy is to assess the whole body distribution of 89Zr-CX-2009, including the uptake (visual and quantitative) in tumor lesions as well as non-tumor tissues, in subjects with unresectable locally advanced or metastatic solid tumors.

    The secondary objectives of the substudy are:
    1.To evaluate the safety of 89Zr-CX-2009;
    2.To evaluate the dosimetry of 89Zr-CX-2009;
    3.To evaluate the correlation of 89Zr-CX-2009 tumor uptake with CD166 expression as assessed in archival tumor sample and/or fresh tumor biopsy;
    4.To assess the heterogeneity of 89Zr CX 2009 tumor uptake within and between subjects;
    5.To characterize the PK profile of CX-2009 with respect to the following analytes:
    •Intact CX-2009 (referring to the prodrug form of CX-2009 ± DM4);
    •Total CX-2009 (intact and activated forms of CX-2009 ± DM4);
    •Total CX-2009-conjugated DM4 (antibody conjugated-DM4);
    •Free DM4;
    •S-methyl DM4 (DM4-Me) - a DM4 metabolite with potent cytotoxic activity.
    6. To characterize the PK profile of 89Zr-CX-2009.

    The exploratory objectives of the substudy are:
    1.To evaluate the correlation between tumor uptake of 89Zr-CX-2009 and response to therapy on lesions level and on subject level;
    2.To characterize the CD166 expression, protease activity, and activation of CX-2009 in on-treatment tumor biopsies and peripheral blood, respectively.

    This substudy will only be conducted in the VUMC (The Netherlands)
    E.3Principal inclusion criteria
    1. Histologically confirmed diagnosis of active metastatic or locally
    advanced unresectable solid tumor in subjects who have disease
    progression after treatment with available therapies that are known to
    confer clinical benefit, or who are intolerant to treatment in following
    indications:
    Eligible indications, by Part:
    Part A: BC, CRPC, NSCLC (including adenocarcinoma and squamous cell
    subtypes), OEC, EC, HNSCC, and CCC;
    Part A2: BC, NSCLC (including adenocarcinoma and squamous cell
    subtypes), OEC,EC, and HNSCC;
    Parts B, C2, and D2: TNBC, hormone receptor (HR; ie, estrogen and/or
    progesterone)-positive/HER2-negative BC, NSCLC (including
    adenocarcinoma and squamous cell subtypes), OEC, and HNSCC; and
    Parts A mTPI-2 cohort, C1, and D1: BC, NSCLC (including
    adenocarcinoma and squamous cell subtypes), and HNSCC;
    Criterion specific to Parts B, C, and D:
    Subjects must have received the standard prior treatments for
    metastatic or advanced unresectable disease as outlined below, but not
    more than 3 (≤3) prior lines in total;
    2. Agrees to provide tumor tissue, archival, new or recent acquisition
    confirmed to be available prior to initiation of study drug for
    performance of correlative tissue and cellular studies from a tumor site
    not previously irradiated
    3. Evaluable or measurable disease required for dose escalation (Part A)
    and measurable disease per RECIST v1.1 required for Parts A2, B, C1, C2,
    D1 and D2
    4. Subjects with treated brain metastases are eligible if the brain
    metastases are stable and the subject does not require radiation
    therapy, or steroids. Active screening for brain metastases (eg, brain
    computed tomography or magnetic resonance imaging) is not required;
    5. At least 18 years of age;
    6. Eastern Cooperative Oncology Group performance status of 0 or 1;
    7. Anticipated life expectancy of at least 3 months;
    8. screening lab values must meet following criteria: absolute neutrophil
    count >=1500μl; platelet count >= 100 x 10³/μl (must not have been
    transfused within prev. 10 days); hemoglobin >=9.0 g/dL (may have
    been transfused); serum creatinine <= 1.5 x institution upper limit of
    normal (ULN); aspartate aminotransferase (AST) <= 2.5xinstitution's
    ULN; alanine aminotransferase (ALT) <= 2.5x institution's ULN (AST,
    ALT <5 x ULN for subjects with CCC and liver metastases); and serum
    total bilirubin <= 1.5x institutional ULN (total bilirubin must be <=3x
    institution's ULN in subjects with Gilbert's syndrome). Serum total
    bilirubin <= 3.0 x institutional ULN for subjects with CCC and liver
    metastasis
    For Parts B, C, D only: Hemoglobin >= 9.0 g/dL (without transfusion
    within 30 days of Cycle 1
    Day 1); AST, ALT, and alkaline phosphatase (ALP) <=2.5 × institution's
    ULN (without exemption for liver or bone metastases); International
    normalized ratio (INR) and activated partial thromboplastin time
    (aPTT) <= 1.5 × ULN (unless subject is on therapeutic anticoagulation,
    at which time the INR and aPTT must be in the target therapeutic
    anticoagulation range); and Serum albumin >=2.5 g/dL.
    9. Women of childbearing potential (defined as women who have
    experienced menarche and who are not permanently sterile or
    postmenopausal; postmenopausal is defined as 12 consecutive months
    with no menses without an alternative medical cause), and males must
    agree to use a highly effective method of contraception prior to study
    entry, while on study drug and for a period of 50 days after the last dose
    of CX2009 or 6 months after the last dose of CX072 whichever is later;
    highly effective methods of contraception which result in a low failure
    rate (ie <1 % per year) when used consistently and correctly include
    implants, injectables, combined hormonal contraceptives, some IUD's,
    sexual abstinence or a vasectomized partner - True abstinence, when
    in line with the preferred and usual lifestyme of the subjects is
    considered a highly effective method only if defined as refraining from
    heterosexual intercourse during the entire period of risk associated with
    the study treatments. (periodic abstinence and withdrawal are not
    acceptable methods of contraception)
    10. The ability to understand and the willingness to sign a written
    informed consent document and adhere to study schedule and
    prohibitions
    E.4Principal exclusion criteria
    1. Neuropathie > grade 1
    2. Active chronic corneal disorder, including but not limited to the following: sjogren's syndrome, Fuchs corneal dystropathy (requiring treatment), history of corneal transplantation, active herpetic keratitis, and also active ocular conditions requiring ongoing treatment/monitoring such as wet age-related macular degeneration requiring intravitreal injections, active diabetic retinopathy with macular edema, presensce of papilledema and acquired monocular vision
    3. Serious concurrent illness, including, but not limited to following:
    - clinically relevant active infection including known active hepatitis B or C. HIV infection or CMV infection or any other known concurrent infectious disease requiring IV antibiotic, antiviral or antifungal therapy within 2 weeks of study enrollment
    - history of or current active autoimmune diseases, including but not limited to myasthenia gravis, inflammatory bowel diseases, RA, autoimmune thyroiditis which is not a sequela of prior immune checkpoint therapy, autoimmune hepatitis, systemic sclerosis, systemic lupus erythematosus, autoimmune vasculitis, autoimmune neuropathies or type 1 insuline dependent diabetes mellitus
    - significant cardiac disease such as recent MI (<= 6 months prior to day 1), unstable angina pectoris, uncontrolled congestive heart failure (NY Heart association >class II), uncontrolled hypertension (NCI CTCAE v.4.03 grade 3 or higher), uncontrolled cardiac arrythmias, severe aortic stenosis or >= grade 3 cardiac toxicity following prior chemotherapy
    - History of multiple sclerosis or other demyelinating disease, Eaton-Lambert syndrome (para-neoplastic syndrome), history of hemorrhagic or ischemic stroke within the last 6 months, or alcoholic liver disease
    - Non-healing wound(s) or ulcer(s) except for ulcerative lesions caused by the underlying neoplasm
    - Psychiatric illness/social situations that would limit compliance with study requirements
    - Interstitial lung disease irrespective of etiology
    4. Advanced or metastatic Stage IV NSCLC subjects with EGFR or ALK genomic alterations unless they have progressed on treatment with appropriate targeted therapy, including osimertinib for T790M mutation-positive NSCLC
    5. Any other anti-cancer treatment such as chemotherapy, immunotherapy, biochemotherapy, radiotherapy, investigative therapy, or high-dose steroids within 30 days of receiving study drug. Low-dose steroids, luteinizing hormone-releasing hormone, aromatase inhibitors (eg, anastrozole), at doses that have been stable for 30 days are permitted for subjects with CRPC
    6. History of severe allergic or anaphylactic reactions to previous mAb therapy
    7. Prior treatment with maytansinoid-containing drug conjugates
    8. Subjects with a previously documented absence of thiol-S-purine methyltransferase activity
    9. Unresolved acute toxicity NCI CTCAE v4.03 Grade >1 (or baseline, whichever is greater) from prior anti-cancer therapy. Alopecia and other non-acute toxicities are acceptable
    10. History of malignancy that is active within the previous 2 years except for localized cancers that are not related to the current cancer being treated, are considered to have been cured and in the opinion of the Investigator, present a low risk for recurrence, including basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the prostate, cervix or breast
    11. Currently receiving anticoagulation therapy with warfarin
    12. The subject has undergone major surgery (requiring general anesthesia) within 3 months prior to dosing. Subjects who have undergone major surgery within this time period may be enrolled, after consultation with the medical monitor
    13. Subjects who have received a live vaccine 28 days prior to the planned first dose of CX-2009
    14. Participating in an ongoing clinical study involving treatment with medications, radiation, or surgery
    15. Women who are pregnant or breast feeding
    16. Subjects who are >20% below their ideal body weight
    FOR PART D1 AND D2
    17. History of myocarditis regardless of the cause;
    18. History of intolerance to prior ICI therapy defined as the need to
    discontinue treatment due to an irAE;
    19. History of any syndrome or medical condition that requires
    treatment with systemic steroids
    (≥10 mg daily prednisone equivalents) or immunosuppressive
    medications. However,
    subjects who require brief courses of steroids (eg, as prophylaxis for IV
    contrast or for
    treatment of an allergic reaction) may be eligible with Sponsor approval.
    Inhaled or topical
    steroids are permitted;
    20. History of allogeneic tissue/solid organ transplant, stem cell
    transplant, or bone marrow
    transplant.
    E.5 End points
    E.5.1Primary end point(s)
    Dose-limiting toxicities
    Study-drug related AEs and AEs leading to discontinuation
    Changes from baseline in clinical laboratory results and vital signs
    E.5.1.1Timepoint(s) of evaluation of this end point
    Administrative interim analyses on safety and efficacy or on PK, immunogenicity, and selected biomarkers may be performed at several times prior to completion of the study in order to facilitate program decisions and to support study presentations or publications
    E.5.2Secondary end point(s)
    Part A
    The secondary objectives of Part A are:
    •Evaluate preliminary efficacy in subjects treated with CX-2009 as
    monotherapy on the basis of:
    ORR by the RECIST Version 1.1, Time to tumor response (TTR), Duration
    of response (DOR), Progression-free survival (PFS), Overall survival
    (OS)
    •Characterize PK of CX-2009 with respect to the following analytes:
    - Intact CX-2009 (referring to the prodrug form of CX-2009 DM4)
    - Total CX-2009 (intact and activated forms of CX-2009 DM4)
    - Total CX-2009-conjugated DM4 (antibody conjugated-DM4)
    - Free DM4
    - S-methyl DM4 (DM4-Me), a DM4 metabolite with potent cytotoxic
    activity;
    •Assess the incidence of ADA formation to CX-2009
    Part A2
    The secondary objectives of Part A2 are to determine:
    •Evaluate preliminary efficacy in subjects treated with CX-2009 as
    monotherapy on the basis of:
    - ORR by the RECIST Version 1.1; TTR; DOR; PFS; and OS
    •Characterize the PK of CX-2009 with respect to the following analytes:
    - Intact CX-2009
    - Total CX-2009
    - Total CX-2009-conjugated DM4
    - Free DM4
    - DM4-Me
    •Assess the incidence of ADA formation to CX-2009
    Part B
    The secondary objectives of Part B are to:
    •Obtain additional characterization of the safety of CX-2009 at the
    MTD/RP2D
    •Evaluate efficacy in subjects treated with CX-2009 as monotherapy on
    the basis of:
    - DOR; TTR; PFS; and OS
    •Characterize the PK of CX-2009 with respect to the following analytes:
    - Intact CX-2009
    - Total CX-2009
    - Total CX-2009-conjugated DM4
    - Free DM4
    - DM4-Me
    •Assess the incidence of ADA formation to CX-2009
    Part C1
    The secondary objectives of Part C1 are
    •Evaluate preliminary clinical activity in subjects treated with CX-2009
    as monotherapy on the basis of:
    - ORR by the RECIST Version 1.1;TTR; DOR; PFS; and OS;
    •Characterize the PK of CX-2009 with respect to the following analytes:
    - Intact CX-2009
    - Total CX-2009
    - Total CX-2009-conjugated DM4
    - Free DM4
    - DM4-Me
    •Assess the incidence of ADA formation to CX-2009
    Part C2
    The secondary objectives of Part C2 are to:
    •Obtain additional characterization of the safety of CX-2009 at the
    MTD/RP2D
    •Evaluate clinical activity in subjects treated with CX-2009 as
    monotherapy on the basis of:
    - DOR;TTR;PFS; and OS;
    •Characterize the PK of CX-2009 with respect to the following analytes:
    - Intact CX-2009
    - Total CX-2009
    - Total CX-2009-conjugated DM4
    - Free DM4; and
    - DM4-Me; and
    •Assess the incidence of ADA formation to CX-2009.
    Part D1
    The secondary objectives of Part D1 are to determine
    •Evaluate preliminary efficacy in subjects treated with CX-2009 plus CX-
    072 on the basis of: ORR by the RECIST Version 1.1; ORR by immunerelated
    RECIST (irRECIST) as defined in the Core; TTR;DOR;PFS;OS;
    •Characterize PK of CX-2009 when it is administered in combination with
    CX-072:
    - Intact CX-2009
    - Total CX-2009
    - Total CX-2009-conjugated DM4
    - Free DM4
    - DM4-Me
    •Assess the incidence of ADA formation to CX-2009 when it is
    administered in combination with
    CX-072
    • Characterize the PK profile of CX-072 when it is administered in
    combination with CX-2009
    •Assess the incidence of ADA formation to CX-072 when it is
    administered in combination with CX-
    2009
    Part D2
    The secondary objectives of Part D2 are:
    • Obtain additional characterization of the safety of CX-2009
    administered with CX-072 at the
    MTD/RP2D;
    • Evaluate efficacy in subjects treated with CX-2009 plus CX-072 on the
    basis of: DOR;TTR;PFS; and OS;
    • Characterize the PK of CX-2009 when it is administered in combination
    with CX-072 with respect to
    the following analytes:
    -Intact CX-2009
    -Total CX-2009
    -Total CX-2009-conjugated DM4
    -Free DM4
    -DM4-Me
    • Assess the incidence of ADA formation to CX-2009 when it is
    administered in combination with
    CX-072
    • Characterize the PK profile of CX-072 when it is administered in
    combination with CX-2009
    • Assess the incidence of ADA formation to CX-072 when it is
    administered in combination with
    CX-2009
    E.5.2.1Timepoint(s) of evaluation of this end point
    Administrative interim analyses on safety and efficacy or on PK, immunogenicity, and selected biomarkers may be performed at several times prior to completion of the study in order to facilitate program decisions and to support study presentations or publications
    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 Yes
    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.8.2.4Number of treatment arms in the trial1
    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 EEA16
    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
    Germany
    Netherlands
    Spain
    United Kingdom
    United States
    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
    LPLV
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months6
    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: 200
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 100
    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 state15
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 300
    F.4.2.2In the whole clinical trial 563
    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
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2017-07-12
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-02-15
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2020-09-10
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