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    Summary
    EudraCT Number:2019-003337-41
    Sponsor's Protocol Code Number:CS1003-305
    National Competent Authority:Poland - Office for Medicinal Products
    Clinical Trial Type:EEA CTA
    Trial Status:Trial now transitioned
    Date on which this record was first entered in the EudraCT database:2019-12-17
    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 ConcernedPoland - Office for Medicinal Products
    A.2EudraCT number2019-003337-41
    A.3Full title of the trial
    A Multi-Center, Double-Blind, Randomized, Phase III Study to Investigate the Efficacy and Safety of CS1003 in Combination with Lenvatinib Compared to Placebo in Combination with Lenvatinib as First-Line Therapy in Subjects with Advanced Hepatocellular Carcinoma (HCC)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study to Investigate the Efficacy and Safety of CS1003 in Combination with Lenvatinib Compared to Placebo in Combination with Lenvatinib in Subjects with advanced liver cancer
    A.4.1Sponsor's protocol code numberCS1003-305
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT04194775
    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 SponsorCStone Pharmaceuticals (Suzhou) Co., Ltd.
    B.1.3.4CountryChina
    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 supportCStone Pharmaceuticals (Suzhou) Co., Ltd.
    B.4.2CountryChina
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationCStone Pharmaceuticals (Suzhou) Co., Ltd.
    B.5.2Functional name of contact pointTrial Information
    B.5.3 Address:
    B.5.3.1Street AddressE168, 2nd Floor, 218 Xinghu Str., A1 Building, North Block, BioBay, Suzhou Industrial Park
    B.5.3.2Town/ citySuzhou
    B.5.3.3Post code215123
    B.5.3.4CountryChina
    B.5.6E-mailCS1003-305EU@cstonepharma.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 nameCS1003
    D.3.2Product code CS1003
    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 INNNofazinlimab
    D.3.9.2Current sponsor codeCS1003
    D.3.9.3Other descriptive nameCS1003
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboConcentrate for solution for infusion
    D.8.4Route of administration of the placeboIntravenous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    unresectable advanced hepatocellular carcinoma
    E.1.1.1Medical condition in easily understood language
    liver cancer
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level LLT
    E.1.2Classification code 10019828
    E.1.2Term Hepatocellular carcinoma non-resectable
    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 compare the efficacy of CS1003 in combination with lenvatinib vs. placebo in combination with lenvatinib
    E.2.2Secondary objectives of the trial
    - To compare the efficacy of CS1003 in combination with lenvatinib vs. placebo in combination with lenvatinib
    - To compare the safety of CS1003 in combination with lenvatinib vs. placebo in combination with lenvatinib
    - To characterize the population pharmacokinetics (PopPK) and immunogenicity of CS1003 when dosed in combination with lenvatinib
    - To evaluate the disease/treatment-related patient-reported outcome (PRO), Health related Quality of Life (HRQoL)/Global health status (GHS) and function of subjects treated with CS1003 in combination with lenvatinib compared to placebo in combination with lenvatinib
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1.Age ≥18 years on the day of signing informed consent (For Taiwan, the lower limit of age is 20 years).
    2.Subjects with unresectable advanced HCC that is not eligible for
    surgery and/or locoregional therapy (Stage B or C based on Barcelona
    Clinic Liver Cancer [BCLC] staging system) and meets either one of the following criteria: 1) histologically or cytologically confirmed diagnosis of HCC, 2) clinically confirmed diagnosis of HCC according to American Association for the study of Liver Diseases (AASLD) criteria.
    3. With at least one measurable lesion can be assessed.
    4. Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1.
    5. Life expectancy ≥ 3 months.
    6. Child-Pugh A.
    7. No prior systemic treatment for advanced HCC.
    8. Subjects with hepatitis B virus (HBV) infection are willing to continue receiving antiviral treatment while on study.
    9. Subjects have adequate organ and marrow function.
    10. Female subjects with childbearing potential must have negative serum pregnancy test result at screening. Female subjects with childbearing potential, and male subjects and their female partners with childbearing potential must agree to use a contraceptive method(s) detailed in the protocol from the day of signing informed consent form (ICF), during the study and till at least 6 months after the last dose.
    E.4Principal exclusion criteria
    1.Fibrolamellar HCC, sarcomatoid HCC, cholangiocellular carcinoma or mixed cholangiocarcinoma and HCC.
    2. A prior bleeding event due to esophageal or gastric varices within 6 months or other gastrointestinal bleeding events within 28 days prior to
    screening. Untreated or incompletely treated esophageal or gastric varices that are considered by the investigator to be at high-risk for
    bleeding (Note: Patients must undergo an esophagogastroduodenoscopy [EGD], and all size of varices [small to large] must be assessed and
    treated per local standard of care prior to enrollment; patients who have undergone an EGD within 6 months prior to the initiation of study
    treatment do not need to repeat the procedure). Active gastric or duodenal ulcer.
    3. Malabsorption syndrome or inability to take oral medication due to
    other causes.
    4. HBV and HCV co-infection.
    5. Surgery or locoregional therapy for palliative purpose (e.g., to treat
    bone metastases or metastases causing nerve impingement) within 4
    weeks prior to study treatment.
    6. History of other malignancy(ies) in the past 5 years, except for
    malignant disease treated with curative intent and without active
    disease.
    7. Known history of human immunodeficiency virus (HIV) infection or
    acquired immunodeficiency syndrome (AIDS).
    8. Current or prior use of systemic corticosteroid (> 10 mg/day
    prednisone or equivalent) or other immunosuppressive medication
    within 14 days prior to the first dose of study treatment.
    9. History of bone marrow transplantation or organ transplantation.
    10. History of anaphylaxis or hypersensitivity to any ingredient of the
    investigational product.
    11. Any contraindication of lenvatinib.
    12.Known history of drug abuse that would interfere with cooperation with the requirements of the trial.
    13. Pregnant or lactating female subjects.
    14. History of psychiatric disease that would interfere with cooperation with the requirements of the trial; lack of or with restricted physical capability.
    15. QTc interval > 470 msec (as calculated with Fridericia's formula) at
    screening electrocardiogram (ECG);
    16. Any condition that would in the investigator's judgment, prevent the subject from participating in this study.
    E.5 End points
    E.5.1Primary end point(s)
    * Primary endpoint: Overall survival (OS)
    * Estimand: The primary objective will be evaluated under the treatment
    policy strategy to reflect the effect of the initially assigned randomized
    study treatment, irrespective of intercurrent events such as
    discontinuing treatment, withdrawing from or dropping out of the study
    and starting of non-protocol anti-cancer treatment. The population-level summary for OS will be estimated by the HR from stratified Cox
    regression model together with its corresponding 95% CI and stratified
    logrank p-value for the ITT set.
    E.5.1.1Timepoint(s) of evaluation of this end point
    * From randomization to death, loss to follow-up or end of study,
    whichever occurs first.
    E.5.2Secondary end point(s)
    Key secondary endpoints:
    * Objective response rate (ORR) assessed by Blinded Independent
    Central Review Committee (BICR)
    * Estimand: ORR assessed by BICR will be evaluated under the modified
    while-on-treatment strategy using tumor assessments prior to initiating
    non-protocol anti-cancer treatment to reflect the effect of the initially
    assigned randomized study treatment. The population-level summary for
    ORR evaluated by BICR will be presented by the rate difference between
    the two groups and the corresponding 95% CI using normal
    approximation to the binomial distribution, and p-value calculated by
    Stratified Mantel-Haenszel test for the ITT set.
    * Progression-free survival (PFS) assessed by BICR based on Response
    Evaluation Criteria in Solid Tumors (RECIST) v1.1
    * Estimand: PFS assessed by BICR will be evaluated under the treatment
    policy strategy to reflect the effect of the initially assigned randomized
    study treatment, irrespective of intercurrent events such as
    discontinuing treatment before BICR assessed disease progression and
    starting of non-protocol anti-cancer treatment before disease
    progression. The population-level summary for PFS evaluated by BICR
    will be estimated by the hazard ratio (HR) from stratified Cox regression
    model together with its corresponding 95% CI and stratified logrank p-
    value for the ITT set.
    Other secondary endpoints
    * PFS evaluated by investigator based on RECIST v1.1.
    * ORR evaluated by investigators based on RECIST v1.1
    * Duration of response (DoR) and disease control rate (DCR) evaluated
    by BICR and investigators based on RECIST v1.1
    * Adverse events (AEs), serious adverse events (SAEs), death, vital
    signs including blood pressure and pulse, etc., electrocardiogram (ECG),
    laboratory tests (including serum chemistry, hematology and urinalysis,
    etc.) and ECOG performance status etc.
    * Peak and trough serum concentrations of CS1003
    * Number and percentage of subjects who develop anti-CS1003 antibody
    (ADA)
    * Time to deterioration (TTD), defined as the time from randomization to
    the first deterioration of EORTC QLQ-C30 scale
    E.5.2.1Timepoint(s) of evaluation of this end point
    From randomization to progression of disease (PD), the start of new
    anti-cancer treatment, subject withdraws informed consent, death, or
    end of study, whichever occurs first.
    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 Yes
    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
    Immunogenicity
    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 No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    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) No
    E.8.2.2Placebo Yes
    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 concerned6
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA25
    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
    Taiwan
    China
    United States
    Italy
    Poland
    Spain
    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 end when the number of events reaches the target for final OS analysis, or when Sponsor terminates this study, whichever occurs first.
    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 months2
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years4
    E.8.9.2In all countries concerned by the trial 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: 260
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 265
    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 state26
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 26
    F.4.2.2In the whole clinical trial 534
    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)
    Subjects potentially benefiting from the study treatment may continue to receive study treatment after treatment period is completed until
    progression of disease, unacceptable toxicity, initiation of other anti-cancer treatment, lost to follow-up, death or end of the study,
    whichever occurs 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 Decision2020-03-06
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-01-15
    P. End of Trial
    P.End of Trial StatusTrial now transitioned
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