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    Summary
    EudraCT Number:2019-004624-38
    Sponsor's Protocol Code Number:BOT112-02
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2020-03-06
    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 ConcernedSpain - AEMPS
    A.2EudraCT number2019-004624-38
    A.3Full title of the trial
    Phase IIa open-label clinical study of intratumoural administration of BO-112 in combination with pembrolizumab in subjects with liver metastasis from colorectal cancer or gastric/gastro-oesophageal junction cancer
    Estudio clínico abierto de fase IIa de administración intratumoral de BO-112 en combinación con pembrolizumab en sujetos con metástasis hepáticas por cáncer colorrectal o cáncer gástrico/de la unión gastroesofágica.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study of BO-112 with pembrolizumab for colorectal or gastric /gastro-oesophageal junction cancer with liver metastasis
    Estudio de BO-112 con pembrolizumab para el cáncer colorrectal o gástrico/de la UGE con metástasis hepáticas.
    A.4.1Sponsor's protocol code numberBOT112-02
    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 SponsorBioncotech Therapeutics, S.L
    B.1.3.4CountrySpain
    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 supportBioncotech Therapeutics, S.L.
    B.4.2CountrySpain
    B.4.1Name of organisation providing supportMerck Sharp & Dohme International GmbH
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationPivotal S.L.
    B.5.2Functional name of contact pointClinical operations
    B.5.3 Address:
    B.5.3.1Street AddressCalle Gobelas, 19
    B.5.3.2Town/ cityMadrid
    B.5.3.3Post code28023
    B.5.3.4CountrySpain
    B.5.4Telephone number+34917081250
    B.5.6E-mailmaria.moreno@pivotalcr.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 nameBO-112
    D.3.2Product code BO-112
    D.3.4Pharmaceutical form Suspension for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntratumoral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPolyinosinic:Polycytidylic acid
    D.3.9.2Current sponsor codeBO-112
    D.3.9.3Other descriptive namePoly I:C
    D.3.9.4EV Substance CodeSUB177592
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number0.6
    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 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 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
    D.2.1.1.2Name of the Marketing Authorisation holderMerck Sharp & Dohme B.V
    D.2.1.2Country which granted the Marketing AuthorisationSpain
    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 MK-3475
    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 INNPembrolizumab
    D.3.9.2Current sponsor codeMK-3475
    D.3.9.4EV Substance CodeSUB167136
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Colorectal cancer or gastric/gastro-oesophageal junction cancer with liver metastasis
    Cáncer colorrectal o gástrico/de la unión gastroesofágica con metástasis hepáticas.
    E.1.1.1Medical condition in easily understood language
    Colorectal cancer or gastric/gastro-oesophageal junction cancer with liver metastasis
    Cáncer colorrectal o gástrico/de la unión gastroesofágica con metástasis hepáticas.
    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 10063916
    E.1.2Term Metastatic gastric 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 21.0
    E.1.2Level LLT
    E.1.2Classification code 10052362
    E.1.2Term Metastatic colorectal 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 No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    • Investigation of the anti-tumour efficacy and safety of repeated IT administrations of BO-112 in metastatic liver lesions in combination with IV pembrolizumab
    •Investigación de la eficacia antitumoral y la seguridad de las administraciones IT repetidas de BO-112 en lesiones hepáticas metastásicas en combinación con pembrolizumab por vía IV.
    E.2.2Secondary objectives of the trial
    • Further characterisation of safety and of clinical activity of the combination as well as determination of systemic exposure of BO-112
    • Exploratory: Evaluation of antitumoural and immunological effects in the TME of the injected lesion
    •Caracterización adicional de la seguridad y la actividad clínica de la combinación, así como determinación de la exposición sistémica de BO 112.
    •Exploratorio:Evaluación de los efectos antitumorales e inmunológicos en el MET de la lesión inyectada.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1.Be willing and able to give written informed consent for the study.
    2.Be equal or greater than 18 years of age.
    3.Have nonresectable liver metastasis(es) of colorectal or gastric/gastro-oesophageal junction cancer (GC/GEJ).
    4.Have progressed during or after, or have not tolerated therapy for advanced/metastatic disease as follows. Colorectal cancer: at least 2 lines of prior therapy (1 line if hepatic recurrence after resection). Gastric or gastro-oesophageal cancer: at least 1 line of prior therapy .
    5.Have at least 1 liver metastasis of minimum 20 mm in diameter that is suitable for intratumoural injection.
    6.Presence of at least 1 measurable lesion according to RECIST v1.1.
    7.Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
    8.Adequate haematologic and end-organ function within 2 weeks prior to the first dose of study treatment
    9.Female subjects who are not pregnant or breastfeeding and at least 1 of the following conditions applies:
    a)Not a woman of childbearing potential (WOCBP)
    b)WOCBP who agrees to follow contraception guidance during the treatment period and for at least 120 days after the last dose of study treatment.
    10.Able and willing to comply with study and follow-up procedures.
    1.Estar dispuesto y ser capaz de dar el consentimiento informado por escrito para el estudio.
    2.Tener 18 años de edad.
    3.Tener metástasis hepáticas no resecables de cáncer colorrectal o gástrico/de la unión gastroesofágica (CG/UGE).
    4.Haber experimentado progresión durante o después o no haber tolerado el tratamiento para la enfermedad avanzada/metastásica de la siguiente forma. Cáncer colorectal: al menos 2 líneas previas de tratamiento (1 línea si recidiva hepática tras resección. Cáncer gástrico o gastroesofágico: al menos 1 línea previa de tratamiento.
    5.Tener al menos 1 metástasis hepática de un diámetro mínimo de 20 mm que sea adecuada para inyección percutánea intratumoral.
    6.Presencia de al menos 1 lesión medible según los criterios RECIST v1.1.
    7.Estado funcional del Eastern Cooperative Oncology Group (ECOG) de 0 o 1.
    8.Función hematológica y orgánica adecuada en las 2 semanas anteriores a la primera dosis del tratamiento del estudio.
    9.Mujeres que no estén embarazadas ni en periodo de lactancia y que cumplan al menos 1 de las siguientes condiciones:
    a)No es una mujer en edad fértil
    b)Mujeres en edad fértil que acepten seguir las pautas anticonceptivas durante el período de tratamiento y durante al menos 120 días después de la última dosis del tratamiento del estudio.
    10.Capacidad y voluntad para cumplir con los procedimientos del estudio y de seguimiento
    E.4Principal exclusion criteria
    1.Prior treatment with an immune checkpoint inhibitor, an agent directed to another stimulatory or co-inhibitory T-cell receptor or any Toll-like receptor (TLR) agonist.
    2.Liver metastasis(es) with macroscopic tumour infiltration into the main portal vein, hepatic vein or vena cava.
    3.Contraindications to tumour biopsy and injections of the hepatic metastasis(es).
    4.Chemotherapy, definitive (curative) radiation, or biological cancer therapy within 4 weeks prior to the first dose of study treatment.
    5.Clinically active central nervous system metastases and/or carcinomatosis meningitis.
    6.Life expectancy of < 12 weeks.
    7.Active infection requiring systemic therapy.
    8.History of (non-infectious) pneumonitis that required steroids or current pneumonitis.
    9.Active autoimmune disease that required systemic treatment in past 2 years.
    10.Known human immunodeficiency virus (HIV) infection.
    11.Known history of hepatitis B or known active hepatitis C virus infection.
    12.For WOCBP: pregnancy or a positive urine pregnancy test (eg within 72 hours) prior to treatment; or breastfeeding.
    13.Any other medical condition which would impact the safety of the subject or interfere with the subject’s ability to comply with the study and follow-up procedures.
    14.Is currently participating or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
    1.Tratamiento previo con inhibidor de dianas específicas de células immunes, un agente dirigido a otro receptor de linfocitos T estimulador o coinhibidor o cualquier agonista del receptor de tipo Toll (TLR).
    2.Metástasis hepáticas con infiltración tumoral macroscópica en la vena porta principal, la vena hepática o la vena cava.
    3.Contraindicaciones de la biopsia tumoral e inyecciones de las metástasis hepáticas,
    4.Quimioterapia, radioterapia definitiva (curativa) o tratamiento biológico en las 4 semanas anteriores a la primera dosis del tratamiento del estudio.
    5.Metástasis del sistema nervioso central (SNC) clínicamente activas y/o meningitis por carcinomatosis.
    6.Esperanza de vida <12 semanas.
    7.Infección activa que precise tratamiento sistémico.
    8.Antecedentes de neumonitis (no infecciosa) que requiriera la administración de corticoesteroides o neumonitis actual.
    9.Enfermedad autoinmunitaria activa que haya necesitado tratamiento sistémico en los 2 años anteriores.
    10.Infección por el virus de la inmunodeficiencia humana (VIH).
    11. Antecedentes conocidos de infección por el virus de la hepatitis B o infección por hepatitis C activa conocida
    12. En el caso de las mujeres en edad fértil: embarazo o prueba de embarazo en orina positiva (p. ej., en las 72 horas previas al tratamiento) o lactancia.
    13.Cualquier otra afección médica que pudiera afectar a la seguridad del sujeto o interferir en la capacidad del sujeto para cumplir con el estudio y los procedimientos de seguimiento
    14.Estar participando o haber participado en un estudio con un fármaco en investigación o haber utilizado un dispositivo en fase de investigación en las 4 semanas anteriores a la primera dosis del tratamiento del estudio.
    E.5 End points
    E.5.1Primary end point(s)
    • Efficacy: ORR based on the BOR using RECIST 1.1
    • Safety: number and proportion of subjects with study treatment-related TEAEs with severity ≥ Grade 3 (NCI-CTCAE v 5.0)
    •Eficacia: TRO basada en la MRG usando los criterios RECIST 1.1
    •Seguridad: número y proporción de sujetos con AADT relacionados con el tratamiento del estudio con una intensidad de grado ≥3 (CTCAE del NCI v 5.0)
    E.5.1.1Timepoint(s) of evaluation of this end point
    After stage 1 and at the end of the study
    Tras la etapa 1 y al final del estudio
    E.5.2Secondary end point(s)
    • Safety: number and proportion of subjects with TEAEs (any grade)
    • Safety: number and proportion of subjects with related TEAEs (any grade)
    • Tolerability: number of study discontinuations due to related TEAE
    • Efficacy: disease control rate (DCR = CR, PR and SD of at least 12 weeks duration) using RECIST 1.1
    • Efficacy: ORR based on best overall response using RECIST modified for immune-based therapies (iRECIST)
    • Efficacy: DCR = iCR, iPR + iSD of at least 12 weeks duration) using iRECIST
    • Efficacy: duration of response
    • Efficacy: progression-free survival / overall survival rate at 6 months
    • Pharmacokinetics: systemic exposure after first BO-112 administration
    • Immune cell profile of TME in injected and noninjected lesions
    • Genetic (transcriptomic) analysis of the Tumour microenvironment
    •Seguridad: número y proporción de sujetos con AADT (cualquier grado)
    •Seguridad: número y proporción de sujetos con AADT (cualquier grado)
    •Tolerabilidad: número de abandonos del estudio debido a AADT relacionados
    •Eficacia: tasa de control de la enfermedad (TCE = RC, RP y EE de al menos 12 semanas de duración) según los criterios RECIST 1.1
    •Eficacia: TRO basada en la mejor respuesta global según los criterios RECIST modificados para los tratamientos basados en el sistema inmunitario (iRECIST)
    •Eficacia: TCE = RCi, RPi+ EEi de al menos 12 semanas de duración según iRECIST
    •Eficacia: duración de la respuesta
    •Eficacia: supervivencia sin progresión/ tasa de supervivencia global a los 6 meses
    •Farmacocinética: exposición sistémica después de la primera administración de BO-112
    •Perfil de células inmunitarias del MET en lesiones inyectadas y no inyectadas
    •Análisis genético (transcriptómico) del MET
    E.5.2.1Timepoint(s) of evaluation of this end point
    Several timepoints throughout the study and at the end of the study.
    Varias veces durante el estudio y al final del estudio.
    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 Yes
    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) 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) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    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 EEA15
    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 No
    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 years
    E.8.9.1In the Member State concerned months36
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial months36
    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: 35
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 34
    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 state25
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 69
    F.4.2.2In the whole clinical trial 69
    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)
    none
    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 Decision2020-04-02
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-03-31
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
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