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    The EU Clinical Trials Register currently displays   41039   clinical trials with a EudraCT protocol, of which   6717   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2020-000917-34
    Sponsor's Protocol Code Number:20-214-29/CA045-022
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2020-08-07
    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 ConcernedGermany - BfArM
    A.2EudraCT number2020-000917-34
    A.3Full title of the trial
    A Phase 3, Randomized, Open-label Study to Compare Adjuvant Immunotherapy of Bempegaldesleukin Combined with Nivolumab Versus Nivolumab After Complete Resection of Melanoma in Patients at High Risk for Recurrence (PIVOT-12)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study of bempegaldesleukin plus nivolumab versus nivolumab alone after surgical removal of all known Melanoma lesions in patients at high risk of cancer returning after surgery
    A.3.2Name or abbreviated title of the trial where available
    PIVOT - 12
    A.4.1Sponsor's protocol code number20-214-29/CA045-022
    A.5.4Other Identifiers
    Name:US IND NoNumber:125471
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/273/2020
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorNektar Therapeutics
    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 supportNektar Therapeutics
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationPPD
    B.5.2Functional name of contact pointProject Manager
    B.5.3 Address:
    B.5.3.1Street Address929 North Front Street
    B.5.3.2Town/ cityWilmington
    B.5.3.3Post codeNC 28401-331
    B.5.3.4CountryUnited States
    B.5.4Telephone number+15415089135
    B.5.6E-mailelizabeth.williams@ppdi.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 namebempegaldesleukin (NKTR-214)
    D.3.2Product code bempegaldesleukin (NKTR-214)
    D.3.4Pharmaceutical form Powder for solution for injection
    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 INNBEMPEGALDESLEUKIN
    D.3.9.1CAS number 1939126-74-5
    D.3.9.2Current sponsor codeNKTR-214
    D.3.9.3Other descriptive nameBEMPEGALDESLEUKIN
    D.3.9.4EV Substance CodeSUB196365
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1.0
    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.IMP: 2
    D.1.2 and D.1.3IMP RoleComparator
    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 Yes
    D.2.1.1.1Trade name Opdivo
    D.2.1.1.2Name of the Marketing Authorisation holderBristol-Myers Squibb EEIG
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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 nameNivolumab
    D.3.2Product code BMS-936558
    D.3.4Pharmaceutical form 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 INNNivolumab
    D.3.9.1CAS number 946414-94-4
    D.3.9.3Other descriptive nameNIVOLUMAB
    D.3.9.4EV Substance CodeSUB122750
    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
    Resected Stage IIIA (lymph node metastasis > 1 mm)/B/C/D and IV melanoma with no evidence of disease
    E.1.1.1Medical condition in easily understood language
    Melanoma
    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 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.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective is to compare the efficacy, as measured by RFS (recurrence-free survival) by BICR (blinded independent central review), of bempegaldesleukin plus nivolumab versus nivolumab in patients with completely resected Stage IIIA (LN metastasis > 1 mm), Stage IIIB/C/D, or Stage IV (AJCC 8th edition) cutaneous melanoma with NED (no evidence of disease) who are at high risk for recurrence.
    E.2.2Secondary objectives of the trial
    • Compare the OS of bempegaldesleukin plus nivolumab versus nivolumab in patients with completely resected Stage IIIA (LN metastasis > 1 mm), Stage IIIB/C/D, or Stage IV NED melanoma
    • Evaluate DMFS by Investigator in patients who have Stage IIIA (LN metastasis > 1 mm) or IIIB/C/D melanoma at study entry
    • Assess the overall safety and tolerability of bempegaldesleukin plus nivolumab versus nivolumab in study patients
    • Describe changes in patient-reported outcomes (PROs) as assessed by the global health/quality of life (GH/QoL) and physical functioning subscales of the 30-item European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30)
    •Evaluate the association between PD-L1 expression status and RFS by BICR
    • Assess the efficacy, as measured by RFS by Investigator, of bempegaldesleukin plus nivolumab versus nivolumab in patients with completely resected Stage IIIA (LN metastasis > 1 mm), Stage IIIB/C/D, or Stage IV NED melanoma
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Key Inclusion Criteria:
    • Male or female patients, age 12 years or older at the time of signing the informed consent form (age 18 years or older where local regulations or institutional policies do not allow for patients < 18 years of age to participate).
    • Histologically confirmed Stage IIIA (LN metastasis > 1 mm [i.e., at least one LN metastasis measuring > 1 mm at greatest diameter]), IIIB/C/D, or IV (M1a/b/c/d) cutaneous melanoma by AJCC (8th edition) at study entry that has been completely surgically resected within 12 weeks prior to randomization. Patients with presence of in-transit or microsatellite disease will be allowed if disease has been completely surgically resected. Patients must have been surgically rendered free of disease with negative surgical margins documented, as applicable.
    • Tumor tissue from biopsy or resected disease must be provided to central laboratory for PD-L1 status analysis. Must have PD-L1 expression classification (≥ 1%, < 1%, indeterminate, or not evaluable) prior to randomization.
    • Disease-free status documented by a complete physical examination and imaging studies within 28 days prior to randomization.
    E.4Principal exclusion criteria
    Key Exclusion Criteria:
    • History of ocular/uveal melanoma or mucosal melanoma.
    • Active, known or suspected autoimmune disease. Patients with Type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
    • Conditions requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
    • Prior therapy for melanoma except surgery for the melanoma lesion(s) and/or adjuvant radiation therapy for central nervous system lesions.
    • Prior therapy with interferon, talimogene laherparepvec (Imylgic®), interleukin-2 (IL-2) directed therapy, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T lymphocyte-associated protein 4 antibody (including ipilimumab or any other antibody or drug specifically targeting T cell co-stimulation or checkpoint pathways).
    • Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer or prior melanoma, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast. Consult with the Medical Monitor about other potential exceptions.
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint is RFS by BICR in the ITT population
    E.5.1.1Timepoint(s) of evaluation of this end point
    determined based on the disease recurrence date provided by BICR and is defined as the time between the date of randomization and the date of first recurrence, new primary melanoma (by BICR), or all-cause death, whichever occurs first. A log-rank test stratified by Stage and PD-L1 status will be used to compare RFS between the two treatment arms at an overall alpha level of 0.05 (two-sided). A stratified Cox proportional hazards model with treatment as the single covariate will be used to estimate the hazard ratio and corresponding 95% confidence interval (CI). The Kaplan-Meier method will be used to further summarize RFS, including Kaplan-Meier curves, medians with corresponding 95% CIs, and RFS rates at 6, 12, 18, 24, and every 12 months thereafter with 95% CIs.
    E.5.2Secondary end point(s)
    Secondary endpoints:
    • overall survival (OS)
    • distant metastasis-free survival (DMFS) by Investigator
    • Overall Safety and Tolerability
    • patient-reported outcomes (PROs )
    • PD-L1 expression as a Predictive Biomarker for RFS
    • recurrence-free survival(RFS) by Investigator
    E.5.2.1Timepoint(s) of evaluation of this end point
    • OS: time between the date of randomization and the date of death due to any cause.
    • DMFS by Investigator:time between the date of randomization and the date of first distant metastasis or date of death due to any cause, whichever occurs first.
    • Overall Safety and Tolerability:the incidence of adverse events, serious adverse events, deaths, and laboratory abnormalities in the safety population.
    • PROs : changes from baseline in scores for the GH/QoL and physical functioning subscales of the EORTC QLQ-C30 questionnaire
    • PD-L1 expression as a Predictive Biomarker for RFS:the RFS by BICR endpoints based on PD-L1 expression level.
    • RFS by Investigator: similar to the primary endpoint, but recurrence and new primary melanoma are decided by Investigator.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    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) 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) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group Yes
    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) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    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 concerned27
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA166
    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
    Australia
    Austria
    Czechia
    France
    Germany
    Greece
    Israel
    Italy
    Netherlands
    New Zealand
    Poland
    Portugal
    Romania
    Russian Federation
    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
    The study will be considered complete when the last patient’s last visit has been conducted and the data is mature for overall survival analysis. In the event of early termination of the study, patients on treatment will be offered SoC dosing for up to a total of 1 year for nivolumab (including nivolumab already administered as part of the study), or until one of the following criteria is met, whichever occurs first:
    • Unacceptable toxicity
    • Disease Recurrence
    • Investigator discretion
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years6
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years7
    E.8.9.2In all countries concerned by the trial months0
    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: 715
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 200
    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 state144
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 684
    F.4.2.2In the whole clinical trial 950
    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)
    Study investigational products will not continue to be administered beyond end of study (EOS). Subsequent cancer treatment(s) after EOS can be given per local standard of care measures at the discretion of the treating physician. EOS is defined as no more than 5 years after randomization of the last patient or Sponsor decision to terminate the study, whichever comes first.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2020-10-07
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-10-07
    P. End of Trial
    P.End of Trial StatusOngoing
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