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    Summary
    EudraCT Number:2017-001050-33
    Sponsor's Protocol Code Number:4SC-202-2-2017
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2020-12-15
    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 ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2017-001050-33
    A.3Full title of the trial
    An open-label Phase Ib/ II, multi-center study of 4SC-202 in Combination with Pembrolizumab in Patients with Unresectable Stage III/Metastatic Stage IV Cutaneous Melanoma primary refractory/non-responding to prior Anti-PD-1 Therapy - The SENSITIZE Study
    Studio in aperto, multicentrico, di fase Ib/II di 4SC-202 in combinazione con Pembrolizumab in pazienti con melanoma cutaneo, di stadio III non resecabile o IV metastatico, refrattari primari/non responsivi a precedente terapia con anti-PD-1. Studio SENSITIZE.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    4SC-202 in Combination with Pembrolizumab in Patients with Cutaneous Melanoma - The SENSITIZE Study
    4SC-202 in combinazione con Pembrolizumab in pazienti con melanoma cutaneo - Studio SENSITIZE
    A.3.2Name or abbreviated title of the trial where available
    SENSITIZE
    SENSITIZE
    A.4.1Sponsor's protocol code number4SC-202-2-2017
    A.5.4Other Identifiers
    Name:SENSITIZENumber:4SC-202-2-2017
    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 Sponsor4SC AG
    B.1.3.4CountryGermany
    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 support4SC AG
    B.4.2CountryGermany
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation4SC AG
    B.5.2Functional name of contact pointMARTIN ORLOVIUS
    B.5.3 Address:
    B.5.3.1Street AddressFraunhoferstrasse 22
    B.5.3.2Town/ cityPlanegg-Martinsried
    B.5.3.3Post code82152
    B.5.3.4CountryGermany
    B.5.4Telephone number00498970076340
    B.5.5Fax number00498970076329
    B.5.6E-mailmartin.orlovius@4sc.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 name4SC-202
    D.3.2Product code [BYK456992]
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INN4SC-202
    D.3.9.2Current sponsor codeBYK456992
    D.3.9.3Other descriptive name4SC-202 - DOMATINOSTAT TOSILATE
    D.3.9.4EV Substance CodeSUB48521
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    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) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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 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 Yes
    D.2.1.1.1Trade name KEYTRUDA - 50 MG- POLVERE PER CONCENTRATO PER SOLUZIONE PER INFUSIONE- USO ENDOVENOSO- FLACONCINO (VETRO) 1 FLACONCINO
    D.2.1.1.2Name of the Marketing Authorisation holderMERCK SHARP & DOHME LIMITED
    D.2.1.2Country which granted the Marketing AuthorisationItaly
    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 namePembrolizumab
    D.3.2Product code [non applicabile]
    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 INNPembrolizumab
    D.3.9.1CAS number 1374853-91-4
    D.3.9.2Current sponsor codenon applicabile
    D.3.9.3Other descriptive nameKeytruda
    D.3.9.4EV Substance CodeSUB167136
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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
    Unresectable Stage III/Metastatic Stage IV Cutaneous
    Melanoma
    Melanoma cutaneo di stadio III non resecabile o IV metastatico
    E.1.1.1Medical condition in easily understood language
    Skin tumor which cannot be resected or is metastatic
    Tumore cutaneo che non può essere asportato o è metastatico
    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 LLT
    E.1.2Classification code 10027152
    E.1.2Term Melanoma of skin (malignant)
    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
    The primary objective of the study is to determine safety and tolerability of combination treatment with 4SC-202 and Pembrolizumab in patients with advanced cutaneous malignant melanoma who are primary refractory or non-responding to anti-PD-1 therapy.
    Determinare la sicurezza e tollerabilità del trattamento di combinazione di 4SC-202 e Pembrolizumab in pazienti con melanoma cutaneo maligno in stadio avanzato che siano refrattari primari o non responsivi a terapia con anti-PD-1.
    E.2.2Secondary objectives of the trial
    • Examine preliminary efficacy of combination treatment with 4SC-202 and Pembrolizumab
    • Determine non-tolerated dose (NTD), maximum tolerated dose (MTD) and recommended phase 2 dose (RPTD) of combination treatment with 4SC-202 and Pembrolizumab
    •Characterize pharmacokinetics (PK) of formulation I and formulation II of 4SC-202
    •Characterize the food effect on PK of formulation II of 4SC-202
    • Esaminare in via preliminare l’efficacia del trattamento di combinazione 4SC-202 e Pembrolizumab
    • Determinare la dose non tollerata (NTD), la massima dose tollerata (MTD) e la dose raccomandata per la fase 2 (RPTD) della combinazione 4SC-202 e Pembrolizumab
    • Caratterizzare il profilo farmacocinetico (PK) della formulazione I e della formulazione II di 4SC-202
    • Caratterizzare l’effetto del cibo sul profilo farmacocinetico della formulazione II di 4SC-202.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Signed informed consent must be obtained prior to any study specific procedure.
    1. Male or female patients, age = 18 years (at screening)
    2. ECOG PS 0-1
    3. Patients with unresectable stage III or stage IV cutaneous melanoma, as per AJCC
    staging system (Version 8) (must have been histologically confirmed at least once
    during course of disease)
    4. Patients with metastatic tumor of unknown primary site and histology of melanoma
    are eligible
    5. Patients must be primary refractory or non-responding to the last prior anti-PD-1 therapy (either as monotherapy or in combination with Ipilimumab)
    The following definitions apply:
    i. Primary refractory: Patients not achieving a response of CR, PR or SD (i.e. not achieving disease control)
    ii. Non-responding: Patients not having achieved a response of CR or PR but having achieved SD
    6. Patients must have progressed during last prior anti-PD-1 mono therapy or Ipilimumab/anti-PD-1 combination therapy, and within 6 months after the last dose of either Nivolumab or Pembrolizumab
    7. Patients must have had anti-PD-1 mono therapy or Ipilimumab/anti-PD-1 combination therapy as the last systemic cancer directed treatment consisting of at least two administrations of either Nivolumab or Pembrolizumab and must have received the last anti-PD-1 administration within 6 months prior to ICF signature
    8. Patients must have been tested for BRAF V600 mutation status
    9. Patients with BRAF-mutated melanoma must have had a BRAF-mutation directed therapy, unless they were not considered eligible (e.g. due to contraindications) for such treatment
    10. Measurable disease by CT or MRI per irRECIST 1.1 criteria, with longest diameter for
    non-nodal lesions = 10 mm and = 15 mm in short axis for nodal lesions
    11. At least one tumor site (either primary site or metastasis) must be accessible for sequential biopsies and the patient must consent to 2 mandatory biopsies. This requirement is not applicable for continuous dosing schedules and may be waived by the sponsor in other individual cases
    12. Females of Childbearing Potential must agree to use highly effective contraception from screening to at least four months after the last dose of Pembrolizumab or 4SC-202 (whatever is later)
    Il consenso informato firmato deve essere ottenuto prima di qualunque procedura specifica dello studio.
    1. Pazienti maschi o femmine, di età = 18 anni (allo screening)
    2. ECOG PS 0-1
    3. Pazienti con melanoma cutaneo non resecabile di stadio III o IV, secondo il Sistema di stadiazione AJCC (Versione 8) (deve essere stata confermata istologicamente almeno una volta dalla diagnosi della malattia)
    4. I pazienti con tumore metastatico a sito di insorgenza primario non noto e con diagnosi istologica di melanoma sono eleggibili.
    5. I pazienti devono essere refrattari primari o non-responsivi alla precedente ultima terapia con anti-PD-1 (sia essa monoterapia o terapia di combinazione con Ipilimumab)
    Si applicano le seguenti definizioni:
    i. Refrattari primari: pazienti che non raggiungono una risposta completa (CR), parziale (PR) o stabilità di malattia (SD) cioè che non ottengono un controllo della malattia.
    ii. Non-responsivi: pazienti che non hanno raggiunto una condizione CR o PR ma hanno ottenuto una SD.
    6. Pazienti che siano andati in progressione durante la precedente ultima monoterapia con anti-PD-1 o terapia di combinazione con Ipilimumab/anti-PD-1, e entro i 6 mesi dall’ultima somministrazione di Nivolumab o Pembrolizumab
    7. Pazienti che abbiano ricevuto come ultima terapia sistemica antitumorale specifica, una monoterapia con anti-PD-1 o una terapia di combinazione Ipilimumab/anti-PD-1, comprendente almeno due somministrazioni o di Nivolumab o di Pembrolizumab l’ultima delle quali avvenuta entro i 6 mesi precedenti la firma del consenso informato
    8. Pazienti sottoposti a test per rilevare la presenza di mutazione BRAF V600.
    9. I pazienti con melanoma BRAF-mutato devono aver ricevuto una terapia diretta contro la mutazione BRAF, a meno di controindicazioni a tale tipo di trattamento
    10. Malattia misurabile mediante TC o RMN secondo i criteri irRECIST 1.1, avente, nelle lesioni non linfonodali, un diametro maggiore = 10 mm e, in quelle linfonodali, un asse minore = 15 mm
    11. Almeno una sede tumorale (sia essa primaria o metastatica) deve essere accessibile per biopsie sequenziali e il paziente deve acconsentire a sottoporsi a 2 biopsie obbligatorie. Questo criterio non è applicabile per gli schemi di somministrazione continua e può essere deviato, a giudizio dello sponsor in casi specifici.
    12. Donne potenzialmente fertili devono accettare l’impiego di metodi contraccettivi altamente efficaci, a partire dallo screening fino ad almeno 4 mesi dopo l’ultima dose di 4SC-202 o Pembrolizumab (qualunque dei due sia l’ultimo somministrato).
    E.4Principal exclusion criteria
    1. Patients not consenting to use adequate contraception as required per protocol
    2. Patients currently participating or who have participated in a study of an investigational
    agent, or who are using an investigational device or have done so within 28 days of the
    first dose of study drug.
    3.Patients who achieved a CR or PR, during or after last prior anti-PD-1 mono- or anti-CTLA-4/anti-PD-1 combination therapy
    4. Life expectancy below 3 months
    5. Patients with uveal or mucosal melanoma
    6. Patients with symptomatic brain metastases/CNS involvement
    7. Patients with inadequate organ function, defined as: a) Absolute neutrophil count (ANC) < 1500/µL
    b) Hemoglobin (Hb) < 9 g/dL
    c) Platelet count < 100,000/µL
    d) Potassium outside of normal limits and not correctable with supplements
    e) Serum creatinine > 1.5 x ULN or eGFR < 50 mL/min
    f) ALT and/or AST > 2.5 x ULN
    g) Serum total bilirubin > 1.5 x ULN
    h) LDH > 5 x ULN
    8. Remaining relevant toxicity (excluding alopecia, fatigue) to previous therapy has not resolved to Grade 1
    9. Patients with a history of anti-PD-1 / immune-related adverse drug reactions of Grade 4 or Grade 3 and a high risk of re-occurrence
    10. Prior treatment with a HDAC or LSD1 inhibitor or both
    11. Prior treatment with anti-PD-L1 or anti-PD-L2 agents
    12. Patients with precedent systemic anti-cancer therapy including chemotherapy, endocrine therapy, immunotherapy or who use other investigational agents prior to first study drug administration if no wash-out period of 5 half-lives or 4 weeks has been respected before first study drug administration.
    13. Therapy with agents known to prolong the QT interval and increase the risk of Torsade des pointes, such as certain antibiotics, antidepressants or neuroleptics
    14. Patients who have received a live vaccine within 28 days prior to anticipated first dose of study drug
    15. Patients with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other systemic immunosuppressive medications within 14 days of study drug administration.
    16. Patients with any immunodeficiency disorder
    17. Patients with any active, known or suspected autoimmune disease that might deteriorate when receiving an immunostimulatory agent as judged by the investigator
    18. Patients with a marked baseline prolongation of QT/QTc interval; Long-QTSyndrome
    19. Patients with any active gastrointestinal disorder that could interfere with the absorption of 4SC-202 (as per judgement of the investigator), such as ulcerative colitis, Crohn’s disease, diabetic gastroparesis, or other syndromes characterized by malabsorption
    20. Patients who are unable to take oral medication
    21. Patients with a history of or concurrent other malignancies that require active systemic treatment.
    22. Patients with any other medical, psychiatric or social condition, which in the opinion of the investigator would preclude participation in the trial, pose an undue medical hazard, interfere with the conduct of the trial or interfere with interpretation of the trial results
    23. Women who are pregnant or lactating or who are planning on becoming pregnant during the trial or for 90 days after completion of the trial
    24. Patients with known HIV, acute or chronic active hepatitis B or hepatitis C
    25. Patients with an active systemic infection
    26. Patients with major surgery within the last 4 weeks
    27. Patients with history or current evidence of clinically relevant allergies or hypersensitivity
    28. Patients with significant current cardiovascular disease
    1. Pazienti che non accettano di utilizzare un metodo contraccettivo adeguato come richiesto da protocollo
    2. Pazienti che stanno partecipando o che hanno partecipato ad uno studio clinico con trattamento sperimentale, o che stanno utilizzando un dispositivo sperimentale o lo hanno fatto entro i 28 giorni precedenti la prima somministrazione di farmaco dello studio.
    3. Pazienti che abbiano ottenuto una CR o PR durante o dopo la precedente ultima terapia con anti-PD-1 somministrata in regime di monoterapia o terapia di combinazione anti-CTLA-4/anti-PD-1
    4. Aspettativa di vita inferiore a 3 mesi
    5. Pazienti con melanoma uveale o mucosale
    6. Pazienti con metastasi cerebrali sintomatiche/coinvolgimento del SNC
    7. Pazienti con funzioni d’organo inadeguate, definite come:
    a) Conta assoluta dei neutrofili (ANC) < 1500/µL
    b) Emoglobina (Hb) < 9 g/dl
    c) Conta piastrinica < 100,000/µL
    d) Potassio al di fuori dei limiti di normalità e non correggibile con supplementi
    e) Creatinine sierica > 1.5 x limite superiore di normalità (ULN) or eGFR < 50 ml/min
    f) ALT e/o AST > 2.5 x ULN
    g) Bilirubina totale sierica > 1.5 x ULN
    h) LDH > 5 x ULN
    8. Rilevanti tossicità residue a pregresse terapie che non si siano ridotte ad un grado 1
    9. Pazienti con una storia di reazioni avverse immuno-correlate di grado 4 o 3, a terapie con anti-PD-1 e con elevato rischio di ricorrenza
    10. Trattamento pregresso con inibitore di HDAC o LSD1 o entrambi
    11. Trattamento pregresso con agenti anti-PD-L1 o anti-PD-L2
    12. Pazienti con pregressa terapia anti-tumorale sistemica compresa chemioterapia, terapia endocrina, immunoterapia o con agenti sperimentali prima della somministrazione della prima dose di farmaco, a meno che non sia stato osservato un periodo di wash-out pari a 5 emivite o a 4 settimane prima della prima somministrazione del farmaco dello studio.
    13. Terapia con agenti noti per prolungare l’intervallo QT e aumentare il rischio di Torsade des pointes, come certi antibiotici, antidepressivi o neurolettici
    14. Pazienti che abbiano ricevuto un vaccino vivo nei 28 giorni precedenti la data prevista di somministrazione della prima dose di farmaco dello studio.
    15. Pazienti con una condizione che richieda trattamento sistemico sia con corticosteroidi (> 10 mg/die di prednisone equivalenti) che con altri farmaci immunosoppressivi nei 14 giorni che precedono la somministrazione del farmaco dello studio.
    16. Pazienti con qualunque disturbo da immunodeficienza
    17. Pazienti con qualunque malattia autoimmune attiva, nota o sospetta che, a giudizio dello sperimentatore, possa peggiorare con la somministrazione di un agente immunostimolante
    18. Pazienti con un marcato prolungamento basale dell’intervallo QT/QTc; Sindrome del QT-Lungo
    19. Pazienti con qualunque forma attiva di disordine gastrointestinale che, secondo giudizio dello sperimentatore, possa interferire con l’assorbimento di 4SC-202, come colite ulcerosa, morbo di Crohn, gastroparesi diabetica o altre sindromi caratterizzate da malassorbimento
    20. Pazienti che non sono in grado di assumere farmaci per via orale
    21. Pazienti con concomitanti o pregresse malignità che richiedono un trattamento sistemico attivo.
    22. Pazienti con qualunque altra condizione medica, psichiatrica o sociale che, a giudizio dello sperimentatore potrebbe precludere la partecipazione allo studio, rappresentare un rischio medico eccessivo, interferire con la conduzione dello studio o l’interpretazione dei risultati.
    23. Donne in gravidanza o allattamento o che programmano una gravidanza nel periodo dello studio o fino ai 90 giorni dopo la sua conclusione
    24. Pazienti con condizione nota di HIV, epatite B acuta o cronica attiva o epatite C
    25. Pazienti con un’infezione sistemica attiva
    26. Pazienti con interventi di chirurgia maggiore nelle ultime 4 settimane
    27. Pazienti con una storia o evidenza attuale di allergie clinicamente rilevanti o ipersensibilità
    28. Pazienti con concomitante patologia cardiovascolare significativa
    E.5 End points
    E.5.1Primary end point(s)
    Safety and tolerability of the combination of 4SC-202 and Pembrolizumab will be assessed from adverse events, laboratory tests, vital signs, ECGs, ECOG PS, physical examination and assessment of concomitant medications.
    Sicurezza e tollerabilità della combinazione 4SC-202 e Pembrolizumab saranno valutate da eventi avversi, esami di laboratorio, segni vitali, ECG, PS ECOG, esame obiettivo e valutazione delle terapie concomitanti.
    E.5.1.1Timepoint(s) of evaluation of this end point
    In addition, after completion of enrollment of dose level 2a, formulation II of 4SC-202 will be explored at selected sites in the following dose levels:
    • DL 2b: 200 mg QD 4SC-202 p.o. (continuous dosing for 21 days) + 2 mg/kg Pembrolizumab i.v. (from Cycle 1 Day 1 onwards, once every 3 weeks). Note: In dose level 2b, there is a PK run-in in the week prior to C1D1 with two single dose administrations of 4SC-202 on Day -7 and Day 0.
    • DL 4: 300 mg TDD 4SC-202 p.o. (continuous dosing for 21 days) + 2 mg/kg Pembrolizumab i.v. (from Cycle 1 Day 1 onwards, once every 3 weeks).
    Le tossicità dose-limitanti saranno valutate durante il periodo DLT definito come segue:
    • Schemi di somministrazione intermittente (livelli di dose 1, 2a e 3): il periodo di DLT include i primi 3 cicli rappresentati dal ciclo 1 di monoterapia con 4SC-202 e dai successivi due cicli (ciclo 2 e 3) di terapia combinata 4SC-202 e Pembrolizumab.
    • Schemi di somministrazione continua (livelli di dose 2b e 4): il periodo DLT include i primi due cicli di terapia di combinazione e cioè va dal ciclo 1 giorno 1 al ciclo 2 giorno 21.
    E.5.2Secondary end point(s)
    Preliminary anti-tumor efficacy of treatment with 4SC-202 and Pembrolizumab in terms of response rates and survival when administered in combination will be determined using
    irRECIST.
    Anti-tumor efficacy will be assessed by calculating the following parameters:
    • Objective Response Rate (ORR)
    • Best Overall Response (BOR)
    • Disease Control Rate (DCR)
    • Duration of Response (DOR)
    • Progression Free Survival (PFS)
    • Time to Progression (TTP)
    • Overall Survival (OS)
    Bioavailability of formulation I, formulation II and impact of food on the bioavailability of formulation II will be evaluated in the PK run-in of dose level 2b .
    Pharmacokinetic analysis will be summarized in a separate report which will be included in the Clinical Study Report.
    La valutazione preliminare dell’efficacia anti-tumorale del trattamento di combinazione con 4SC-202 e Pembrolizumab, in termini di percentuale di risposta e sopravvivenza, sarà determinata usando i criteri irRECIST.
    L’efficacia anti-tumorale sarà valutata calcolando i seguenti parametri:
    • Tasso di risposta obiettiva (Objective Response Rate -ORR)
    • Miglior risposta globale (Best Overall Response -BOR)
    • Tasso di controllo della malattia (Disease Control Rate -DCR)
    • Durata della risposta (Duration of Response - DOR)
    • Sopravvivenza libera da progressione (Progression Free Survival - PFS)
    • Tempo alla progressione (Time to Progression -TTP)
    • Sopravvivenza globale (Overall Survival -OS)
    La biodisponibilità delle formulazioni I e II e l’impatto del cibo sulla biodisponibilità della formulazione II saranno valutate nella fase di PK run-in del livello di dose 2b.
    Le analisi farmacocinetiche saranno riepilogate in un report separato contenuto nel Clinical Study Report.
    E.5.2.1Timepoint(s) of evaluation of this end point
    At the end of each 4th cycle, within ± 7days of D1 of C5, C9, C13, C17, etc., and in case of suspected PD (as per local practice)
    Alla fine di ogni 4 ° ciclo, entro ± 7 giorni dal D1 dei C5, C9, C13, C17, ecc., e in caso di sospetta PD (come da pratica clinica)
    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 No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E.7.1.3.1Other trial type description
    dose level definition
    definizione della dose
    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 No
    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 Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.4.1Number of sites anticipated in Member State concerned1
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA7
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
    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
    LSLV
    LVLS
    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 months3
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years3
    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: 18
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 18
    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 state6
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 36
    F.4.2.2In the whole clinical trial 36
    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)
    Standard of care
    Pratica clinica
    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 Decision2018-09-26
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-07-04
    P. End of Trial
    P.End of Trial StatusOngoing
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