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    Summary
    EudraCT Number:2019-003456-36
    Sponsor's Protocol Code Number:CL1-95012-001
    National Competent Authority:Belgium - FPS Health-DGM
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2021-06-10
    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 ConcernedBelgium - FPS Health-DGM
    A.2EudraCT number2019-003456-36
    A.3Full title of the trial
    A first in human Phase 1/2 open-label, multicenter, dose escalation and expansion study of PRS-344/S095012 in patients with solid tumors
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study of PRS-344/S095012 (PD-L1x4-1BB bispecific antibody) in patients with solid tumors
    A.4.1Sponsor's protocol code numberCL1-95012-001
    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 SponsorInstitut de Recherches Internationales Servier
    B.1.3.4CountryFrance
    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 supportADIR
    B.4.2CountryFrance
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationInstitut de Recherches Internationales Servier
    B.5.2Functional name of contact pointClinical Studies Department
    B.5.3 Address:
    B.5.3.1Street Address22 route 128
    B.5.3.2Town/ cityGIF SUR YVETTE
    B.5.3.3Post code91190
    B.5.3.4CountryFrance
    B.5.4Telephone number+33155727718
    B.5.6E-mailclinicaltrials@servier.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 nameS095012
    D.3.2Product code S095012
    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.3.9.2Current sponsor codeS095012
    D.3.9.3Other descriptive namePRS-344
    D.3.9.4EV Substance CodeSUB207152
    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 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.IMP: 2
    D.1.2 and D.1.3IMP Role
    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 Gazyvaro®
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration GmbH
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntrauterine use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNObinutuzumab
    D.3.9.1CAS number 949142-50-1
    D.3.9.4EV Substance CodeSUB32751
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1000
    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
    Advanced and/or metastatic solid tumors
    E.1.1.1Medical condition in easily understood language
    Solid tumors
    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 10065252
    E.1.2Term 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
    Phase 1:
    To evaluate the safety and tolerability profile of single-agent PRS-344/S095012
    To determine the maximum tolerated dose (MTD) if determined, or maximum administered dose (MAD) and the recommended phase 2 dose (RP2D) of PRS-344/S095012

    Phase 2:
    To evaluate the potential anti-tumor activity and efficacy of PRS-344/S095012, as per central assessment according to RECIST v1.1
    criteria based on appropriate clinical standards for the specified tumor type.
    E.2.2Secondary objectives of the trial
    Phase 1:
    To characterize the pharmacokinetics (PK) of PRS-344/S095012
    To evaluate the immunogenicity of PRS 344/S095012
    To assess the preliminary anti-tumor activity of PRS-344/S095012 as per the investigator, according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

    Phase 2:
    To further describe the efficacy, through survival, duration of responses, clinical benefit
    To further characterize the safety and tolerability of PRS-344/S095012 in specific indications
    To further characterize the PK profile of PRS-344/S095012
    To further characterize immunogenicity of PRS-344/S095012
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Age ≥18 years on the day the consent is signed.
    2. Life expectancy of at least 3 months
    3. Patient should have a documented disease progression on prior therapy before entry into this study.
    4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
    5. Royal Marsden Prognosis score of 0 to 1 (score based on lactate dehydrogenase (LDH) value, albumin value and number of sites of metastasis).
    6d. Adequate organ function as assessed by laboratory tests within 7 days prior to pretreatment with obinutuzumab:
    -Lymphocyte count ≥ 800/µ
    -Gamma-globulin level > 6g/L (by serum protein electrophoresis) or IgG level > 4g/L (by measurement of quantitative immunoglobulins).
    7a A female patient must use a highly effective method of birth control during study treatment and until, for 120 days after the last dose of the study treatment. PRS-344/S095012, or 18 months after the last obinutuzumab infusion, whichever comes the latest.
    8a. A male patient with childbearing potential partners must use a condom during the study and for at least 4 months after the last dose of the study treatment., or 6 months after the last Obinutuzumab infusion, whichever comes the latest.
    9a. Test should be negative for cytomegalovirus (CMV), Epstein-Barr virus (EBV), Hepatitis B virus (HBV), and Hepatitis C virus (HCV) infection, according to local standards:
    - Negative CMV DNA testing in serum or plasma by a sensitive quantitative molecular method.
    - Absence of immunoglobulin (Ig)M antibodies against EBV-VCA (Viral Capside Antigen)
    - Negative serologic testing for hepatitis B surface antigen (HbsAg) or a negative result by a sensitive quantitative molecular method for HBV-DNA in serum or plasma
    ­- Negative HCV RNA testing in serum or plasma by a sensitive quantitative molecular method.
    10. Negative test results for human T-lymphotropic virus 1 (HTLV 1).
    HTLV testing is only required for participants from countries in which HTLV 1 infection is endemic (Japan, countries in the Caribbean basin, South America, Central America, sub-Saharan Africa, and Melanesia).

    Dose Escalation:
    11a. Patients with a histological diagnosis of an unresectable, locally advanced or metastatic solid tumor for which standard treatment options are not available, no longer effective, or not tolerated.
    12a. Patients must have measurable disease per RECIST 1.1 as assessed by the local site investigator/imaging. Lesions situated in a previously irradiated area are considered measurable only if progression has been demonstrated in such lesions.
    13b. Patients with no available archived material must have one or more tumor lesions amenable to biopsy

    Dose Expansion:
    14. Patients with histologically diagnosed
    Arm 1 and 2: recurrent, persistent, and/or metastatic cervical cancer.
    Acceptable histologies are squamous carcinoma, adenocarcinoma, and adenosquamous carcinoma.
    -Arm 3: locally advanced or metastatic cutaneous squamous cell
    carcinoma.
    15. Patients must have received :
    Arm 1 (cervical cancer, CPI-naive): at least 1 prior line of platinum­ based combination therapy. Patients must not have received any prior treatment with an immune checkpoint inhibitor (anti-PD-1, PD-L1 or anti-CTLA-4 [cytotoxic T lymphocyte-associated protein 4]) and do not have access to an approved immune checkpoint inhibitor. Surgery, radiation therapy, and additional chemotherapy must not be considered appropriate alternative treatment options for these patients.
    Arm 2 (cervical cancer, CPI-relapsed/refractory): at least 1 prior line of systemic therapy with an immune checkpoint inhibitor as monotherapy or in combination with chemotherapy and/or any other systemic therapies. Surgery, radiation therapy, and additional chemotherapy must not be considered appropriate alternative treatment options for these
    patients.
    Arm 3 (CSCC, CPI-relapsed/refractory): at least 1 prior line of systemic therapy with an immune checkpoint inhibitor as monotherapy or in combination with chemotherapy and/or any other systemic therapies.
    Surgery, radiation therapy, and additional chemotherapy must not be considered appropriate alternative treatment options for these patients.
    16. Biopsy requirements
    ­Arms 1 and 2 (cervical cancer): fresh baseline biopsies are mandatory, on-treatment biopsies are optional.
    ­Arm 3 (skin cancer): fresh baseline biopsies are mandatory, on treatment biopsies are mandatory unless medically contra-indicated.
    17. Patients must have at least one measurable target lesion as per RECIST 1.1 and/or World Health Organization (WHO) criteria for only
    externally visible skin tumors confirmed by central review. Lesions situated in a previously irradiated area are considered measurable only if
    progression has been demonstrated in such lesions.
    E.4Principal exclusion criteria
    1. Patients with previously treated brain metastases may participate provided they are radiologically stable, clinically asymptomatic and are off immunosuppressive therapies for at least 4 weeks. Low dose of steroid (≤10 mg/day prednisone or equivalent) is allowed
    2. Patients who have received prior:
    a. Chemotherapy, small molecule inhibitors, monoclonal antibodies, antibody-drug conjugates, and/or other similar investigational agent: at least 3 weeks or 5 half-lives prior to first IMP administration, whichever is shorter.
    b. Radioimmunoconjugates or other similar experimental therapies at least 6 weeks or 5 half-lives prior to first IMP administration, whichever is shorter.
    3. Patients who have received 4-1BB agonists in the past.
    4. Patients who had a major surgery within 4 weeks prior to first administration of IMP.
    5c. Patients who have received either systemic corticosteroids (> 10 mg per day or equivalent) or other immunosuppressive medications during the 2 months prior to the first dose of the study drug. Higher single doses of corticosteroids given as premedication against infusion-related reactions are allowed. Treatment with local steroids (inhaled, intranasal, injected are allowed.
    6b. Patients with an active infection with a viral, bacterial, or fungal pathogen requiring systemic treatment within seven days before first IMP administration.
    7. Patients with a history of an opportunistic infection within a year prior to first IMP administration.
    8. History of progressive multifocal leukoencephalopathy.
    9. Active tuberculosis requiring treatment within 3 years prior to the start of treatment or a suspicion of latent tuberculosis by the investigator.
    E.5 End points
    E.5.1Primary end point(s)
    Phase 1:
    Incidence of dose-limiting toxicities (DLTs)
    Incidence and severity of adverse events (AEs)
    Discontinuation study treatment due to an AE
    Laboratory, electrocardiogram (ECG) and vital sign measurements

    Phase 2:
    -Arms 1 and 2: OR as per central assessment according to RECIST v1.1 criteria
    -Arm 3: OR as per central assessment and composite response criteria (digital medical photography and/or imaging as per RECIST v1.1)
    E.5.1.1Timepoint(s) of evaluation of this end point
    DLT: End of cycle 1
    Others: All along the study
    E.5.2Secondary end point(s)
    Phase 1:
    Serum PK parameters of PRS-344/S095012
    Detection of antidrug antibodies (ADA) against PRS-344/S095012 and their titration when applicable
    Objective Response (OR): Defined as Complete Response (CR) plus Partial Response (PR)
    Duration of Response (DOR): time from first demonstration of response to progression or death, whichever occurs first.
    Progression-free Survival (PFS): time from the first dose of treatment to first documented disease progression or death due to any cause, whichever occurs first.
    Overall Survival (OS): time from first dose of study drug to death due to any cause.

    Phase2:
    All arms: OR as per investigator assessment, Disease Control (DC), DoR, PFS, OS, Time to Response (TTR)
    AEs, serious adverse events (SAEs), Laboratory, ECG, vital signs
    Serum concentrations of PRS-344/S095012
    Detection of ADA against PRS-344/S095012 and their titration when
    applicable
    E.5.2.1Timepoint(s) of evaluation of this end point
    All along the 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 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 Yes
    E.7.1.3.1Other trial type description
    First in human - combined phase I/II
    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 Yes
    E.8.1.7.1Other trial design description
    Phase I/II
    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 concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA15
    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
    Switzerland
    Australia
    Brazil
    United States
    Belgium
    France
    Spain
    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
    The end of the study is defined as the last patient’s last visit, which includes the long-term safety follow-up visit, 90 days after the last dose of IMP or the last contact attempt if the last participant is declared lost to follow-up.
    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 months4
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years6
    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: 180
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 90
    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 state14
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 102
    F.4.2.2In the whole clinical trial 277
    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 participants' treatment is left to the physician's discretion. As the study drug is not licensed yet at this time, it will not be available on the market.
    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 Decision2021-07-07
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-08-09
    P. End of Trial
    P.End of Trial StatusOngoing
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