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    Summary
    EudraCT Number:2016-002243-42
    Sponsor's Protocol Code Number:GCT1021-01
    National Competent Authority:Denmark - DHMA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2016-07-11
    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 ConcernedDenmark - DHMA
    A.2EudraCT number2016-002243-42
    A.3Full title of the trial
    First-in-human, open-label, dose-escalation trial with expansion cohorts to evaluate safety of Axl-specific antibody-drug conjugate (enapotamab vedotin, HuMax®-AXL-ADC) in patients with solid tumors.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    First-in-human, open-label, dose-escalation trial with expansion cohorts to evaluate safety of Axl-specific antibody-drug conjugate (enapotamab vedotin,HuMax®-AXL-ADC) in patients with solid tumors.
    A.4.1Sponsor's protocol code numberGCT1021-01
    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 SponsorGenmab A/S
    B.1.3.4CountryDenmark
    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 supportGenmab A/S
    B.4.2CountryDenmark
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationGenmab A/S
    B.5.2Functional name of contact pointClinical Trial Information
    B.5.3 Address:
    B.5.3.1Street AddressKalvebod Brygge 43
    B.5.3.2Town/ cityCopenhagen V
    B.5.3.3Post codeDK-1560
    B.5.3.4CountryDenmark
    B.5.4Telephone number+457020 2728
    B.5.5Fax number+457020 2729
    B.5.6E-mailregulatory@genmab.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 nameenapotamab vedotin
    D.3.2Product code IgG1-1021-107-MMAE
    D.3.4Pharmaceutical form Powder for concentrate 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 INNenapotamab vedotin
    D.3.9.1CAS number 1912424-97-5
    D.3.9.2Current sponsor codeIgG1-1021-107-MMAE
    D.3.9.3Other descriptive nameenapotamab vedotin
    D.3.9.4EV Substance CodeSUB182554
    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 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 typeAntibody Drug Conjugate (ADC)
    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
    Cancer of the ovary, cervix, endometrium, anaplastic thyroid, lung (non-small cell lung cancer [NSCLC]) or melanoma
    E.1.1.1Medical condition in easily understood language
    Cancer of the ovary, cervix, endometrium, anaplastic thyroid, lung or skin
    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 HLT
    E.1.2Classification code 10014742
    E.1.2Term Endometrial neoplasms malignant
    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 10008342
    E.1.2Term Cervix carcinoma
    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 10023774
    E.1.2Term Large cell lung 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 10002240
    E.1.2Term Anaplastic thyroid 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 10025650
    E.1.2Term Malignant melanoma
    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 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 20.0
    E.1.2Level PT
    E.1.2Classification code 10039491
    E.1.2Term Sarcoma
    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 21.0
    E.1.2Level PT
    E.1.2Classification code 10014733
    E.1.2Term Endometrial 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 Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To determine the MTD and to establish the safety profile of enapotamab vedotin in a mixed population of patients with specified solid tumors.
    E.2.2Secondary objectives of the trial
    To evaluate the safety laboratory parameters of enapotamab vedotin in a mixed population of patients with specified solid tumors.
    To establish the PK profile and evaluate immunogenicity of enapotamab vedotin after single and multiple infusions.
    To evaluate the antitumor activity of enapotamab vedotinin a mixed population of patients with specified solid tumors.
    To evaluate Axl expression in tumor biopsies from a mixed population of patients with specified solid tumors
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Patients with advanced and/or metastatic cancer:
    - who have failed available standard treatments or
    - who are not candidates for standard therapy.

    Patients must have measurable disease according to Response
    Evaluation Criteria In Solid Tumors (RECIST) version 1.1.
    Have an acceptable renal, liver, and hematological function.

    All patients must provide a tumor tissue sample (Formalin Fixed Paraffin Embedded (FFPE) blocks / slides) from archival tissue or fresh biopsy collected before Cycle 1, Day 1, preferably derived from advanced disease stage.

    Age ≥ 18 years.

    Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

    Life expectancy of at least 3 months.

    Patients, both females and males, of childbearing/reproductive potential must agree to use adequate contraception during and for 6 months after the last infusion of enapotamab vedotin.

    Patients must provide a signed informed consent form.
    E.4Principal exclusion criteria
    Acute deep vein thrombosis or clinically relevant pulmonary embolism, not stable for at least 4 weeks prior to first enapotamab vedotin administration.

    Have clinically significant cardiac disease, including:
    - Onset of unstable angina within 6 months of signing the ICF.
    - Acute myocardial infarction within 6 months of the signing the ICF.

    Known congestive heart failure (Grade III or IV as classified by the New York Heart Association); and/ or a known decreased cardiac ejection fraction of < 45% and/or baseline QT interval as corrected by Fridericia’s formula (QTcF) > 480 msec or uncontrolled atrial fibrillation.

    Uncontrolled hypertension defined as systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg, despite optimal medical management.

    Have received granulocyte colony stimulating factor (G-CSF) or granulocyte/macrophage colony stimulating factor support three weeks prior to first enapotamab vedotin administration.

    Have received a cumulative dose of corticosteroid ≥ 150 mg prednisone (or equivalent doses of corticosteroids) within two weeks before the first enapotamab vedotin administration.

    History of ≥ grade 3 allergic reactions to monoclonal antibody therapy as well as known or suspected allergy or intolerance to any agent given in the course of this trial.

    Major surgery within 4 weeks before first enapotamab vedotin administration.

    Any history of intracerebral arteriovenous malformation, cerebral aneurysm, brain metastases or stroke.

    Any anticancer therapy including; small molecules, immunotherapy, chemotherapy monoclonal antibodies or any other experimental drug within 5 half-lives but maximum 4 weeks before first infusion. Accepted exceptions are bisphosphonates, denosumab and gonadotropin-releasing hormone agonist or antagonist, which can be continued throughout the trial.

    Any prior therapy with a conjugated or unconjugated auristatin derivative/vinca-binding site targeting payload. (Previous treatment with vinca alkaloids is allowed in line with inclusion criterion #1.)

    Radiotherapy within 14 days prior to first enapotamab vedotin administration. (Palliative radiotherapy will be allowed).

    Known past or current malignancy other than inclusion diagnosis, except for:
    - Cervical carcinoma of Stage 1B or less.
    - Non-invasive basal cell or squamous cell skin carcinoma.
    - Non-invasive, superficial bladder cancer.
    - Prostate cancer with a current PSA level < 0.1 ng/mL.
    - Breast cancer in BRCA1 or BRCA2 positive ovarian cancer patients.
    - Any curable cancer with a complete response (CR) of > 2 years duration.

    Melanoma patients with an LDH ≥ 3 x ULN

    Ongoing significant, uncontrolled medical condition including:
    - Serious, non-healing wound, skin ulcer (of any grade), or bone fracture.

    Presence of ≥ grade 2 peripheral neuropathy.

    Clinically significant active viral, bacterial or fungal infection requiring:
    - I.v. treatment with anti-infective therapy that has been administered less than two weeks prior to first dose, or
    - Oral treatment with anti-infective therapy that has been administered less than one week prior to first dose.
    - Prophylactic anti-infective therapy, which is given without clinical symptomatic is allowed (e.g. antibiotic prophylaxis prior to dental extraction, etc.).
    Known human immunodeficiency virus seropositivity.

    Known history / positive serology for hepatitis B (unless immune due to vaccination or resolved natural infection or unless passive immunization due to immunoglobulin therapy):

    Known positive serology for hepatitis C (unless due to immunoglobulin therapy).

    Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the trial or evaluation of the trial result.

    History of organ allograft (except for corneal transplant) or autologous or allogeneic bone marrow transplant, or stem cell rescue within 3 months prior to the first dose of enapotamab vedotin.

    Body weight < 40 kg.

    Women who are pregnant or breast feeding.
    E.5 End points
    E.5.1Primary end point(s)
    Dose Limiting Toxicities (DLTs).

    Adverse events AEs: incidences of AEs, serious adverse events (SAEs), infusion-related AEs ≥ Grade 3 AEs, and AEs related to enapotamab vedotin during the trial.
    E.5.1.1Timepoint(s) of evaluation of this end point
    During the entire study.
    E.5.2Secondary end point(s)
    Safety laboratory parameters (hematology and biochemistry).

    PK parameters (clearance, volume of distribution and area-under-the-concentration-time curve [AUC0-Clast and AUC0-∞], maximum concentration [Cmax], time of Cmax [Tmax], pre dose values, and half-life of enapotamab vedotin and free toxin [MMAE]).

    Immunogenicity of enapotamab vedotin (anti-drug antibodies).

    Anti-tumor activity measured by tumor shrinkage (based on computerized tomography [CT]-scan evaluations), as well as change in CA 125 in patients with ovarian cancer and change in prostate specific antigen (PSA) in patients with castration-resistant prostate cancer (CRPC).

    Objective Response, Progression-Free Survival (PFS), Duration of Response (DoR) and Overall survival (OS).

    Axl expression in the tumor biopsy.
    E.5.2.1Timepoint(s) of evaluation of this end point
    During the entire study.
    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 No
    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 Yes
    E.6.13.1Other scope of the trial description
    Anti-tumor activity
    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) Information not present in EudraCT
    E.8.2.2Placebo Information not present in EudraCT
    E.8.2.3Other Information not present in EudraCT
    E.8.2.4Number of treatment arms in the trial2
    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 EEA20
    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
    Netherlands
    Spain
    Belgium
    Denmark
    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 years4
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years4
    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: 264
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 162
    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 state50
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 210
    F.4.2.2In the whole clinical trial 426
    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)
    Provided in the protocol
    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 Decision2016-09-27
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-10-25
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2021-11-12
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