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    Summary
    EudraCT Number:2022-000339-21
    Sponsor's Protocol Code Number:JK08.1.01
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2022-07-11
    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 ConcernedSpain - AEMPS
    A.2EudraCT number2022-000339-21
    A.3Full title of the trial
    A Phase 1/2, Multicenter, Open Label, Dose Escalation & Dose Expansion Study of JK08, an IL-15 Antibody Fusion Protein Targeting CTLA-4, in Patients with Unresectable Locally Advanced or Metastatic Cancer
    Un estudio de fase 1/2, multicéntrico, abierto, de escalada de dosis y expansión de dosis de JK08, una proteína de fusión de anticuerpos de IL-15 dirigida a CTLA-4, en pacientes con cáncer localmente avanzado o metastásico no resecable
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase 1/2, Multicenter, Open Label, Dose Escalation & Dose Expansion Study of JK08 in Patients with Unresectable Locally Advanced or Metastatic Cancer
    Un estudio de fase 1/2, multicéntrico, abierto, de escalada de dosis y expansión de dosis de JK08 en pacientes con cáncer localmente avanzado o metastásico no resecable
    A.3.2Name or abbreviated title of the trial where available
    6SBT1
    A.4.1Sponsor's protocol code numberJK08.1.01
    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 SponsorSalubris Biotherapeutics, Inc.
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportSalubris Biotherapeutics, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationSalubris Biotherapeutics, Inc.
    B.5.2Functional name of contact pointClinical Program Lead
    B.5.3 Address:
    B.5.3.1Street Address45 W Watkins Mill Rd, Suite E
    B.5.3.2Town/ cityGaithersburg
    B.5.3.3Post codeMD 20878
    B.5.3.4CountryUnited States
    B.5.4Telephone number+13019698650
    B.5.6E-mailnaimish.pandya@salubrisbio.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.3.2Product code JK08
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNNot applicable
    D.3.9.3Other descriptive nameJK08
    D.3.9.4EV Substance CodeSUB273756
    D.3.10 Strength
    D.3.10.1Concentration unit µg/kg microgram(s)/kilogram
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number10 to 300
    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
    Unresectable Locally Advanced or Metastatic Cancer
    Cáncer localmente avanzado o metastásico no resecable
    E.1.1.1Medical condition in easily understood language
    Unresectable Locally Advanced or Metastatic Cancer
    Cáncer localmente avanzado o metastásico no resecable
    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 10061873
    E.1.2Term Non-small cell lung 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 21.1
    E.1.2Level PT
    E.1.2Classification code 10041067
    E.1.2Term Small cell lung 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 21.1
    E.1.2Level LLT
    E.1.2Classification code 10053571
    E.1.2Term Melanoma
    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 24.1
    E.1.2Level PT
    E.1.2Classification code 10085663
    E.1.2Term Clear cell papillary renal cell carcinoma
    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 21.1
    E.1.2Level LLT
    E.1.2Classification code 10077840
    E.1.2Term Urothelial cancer of renal pelvis
    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 21.1
    E.1.2Level PT
    E.1.2Classification code 10067821
    E.1.2Term Head and neck 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 20.0
    E.1.2Level PT
    E.1.2Classification code 10075566
    E.1.2Term Triple negative breast 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 23.0
    E.1.2Level LLT
    E.1.2Classification code 10083238
    E.1.2Term Luminal breast 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 PT
    E.1.2Classification code 10030137
    E.1.2Term Oesophageal adenocarcinoma
    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 PT
    E.1.2Classification code 10061534
    E.1.2Term Oesophageal squamous cell carcinoma
    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 20.0
    E.1.2Level LLT
    E.1.2Classification code 10040810
    E.1.2Term Skin carcinoma
    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 21.1
    E.1.2Level LLT
    E.1.2Classification code 10051971
    E.1.2Term Pancreatic adenocarcinoma
    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 20.0
    E.1.2Level PT
    E.1.2Classification code 10073071
    E.1.2Term Hepatocellular carcinoma
    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 PT
    E.1.2Classification code 10061451
    E.1.2Term Colorectal 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 20.0
    E.1.2Level PT
    E.1.2Classification code 10033128
    E.1.2Term Ovarian 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 21.1
    E.1.2Level LLT
    E.1.2Classification code 10008229
    E.1.2Term Cervical 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 21.1
    E.1.2Level PT
    E.1.2Classification code 10014720
    E.1.2Term Endometrial adenocarcinoma
    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 21.1
    E.1.2Level PT
    E.1.2Classification code 10066474
    E.1.2Term Thyroid 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
    The primary objective of this study is to characterize the safety, tolerability, MTD and/or DLTs of JK08, administered SC on a QW schedule, in patients with unresectable locally, advanced or metastatic cancer in the Dose Escalation Phase, followed by selection and evaluation of RP2D in four planned expansion cohorts.
    El objetivo primario de este estudio es caracterizar la seguridad, tolerabilidad, MTD y/o DLTs de JK08, administrado SC en un esquema QW, en pacientes con cáncer local, avanzado o metastásico no resecable en la fase de escalada de dosis, seguido de la selección y evaluación de RP2D en cuatro cohortes de expansión planificadas.
    E.2.2Secondary objectives of the trial
    The main secondary objectives of the study are to:
    • Characterize the PK of JK08.
    • Assess the immunogenicity (ADA) of JK08.
    • Evaluate the preliminary anti-tumor activity of JK08 as measured by ORR according to standard Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
    • Assess disease control rate (DCR) and progression-free survival (PFS) by RECIST 1.1 and OS.
    Los principales objetivos secundarios del estudio son:
    - Caracterizar la FC del JK08.
    - Evaluar la inmunogenicidad (ADA) del JK08.
    - Evaluar la actividad antitumoral preliminar de JK08 medida por la ORR según los criterios estándar de Evaluación de la Respuesta en Tumores Sólidos (RECIST) 1.1
    - Evaluar la tasa de control de la enfermedad (DCR) y la supervivencia sin progresión (PFS) según los criterios RECIST 1.1 y la SG.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Age ≥ 18 years old.
    2. Signed informed consent
    3. For Dose Escalation, patients with histologically diagnosed unresectable, locally advanced, or metastatic tumor types:
    • Non-small cell lung cancer
    • Small cell lung cancer
    • Melanoma
    • Clear cell or papillary renal cell carcinoma
    • Urothelial cancer
    • Head and neck squamous cell cancer
    • Luminal or triple-negative breast cancer
    • Gastric or gastro-esophageal adenocarcinoma
    • Esophageal squamous cell cancer
    • Skin squamous cell carcinoma
    • Pancreatic adenocarcinoma
    • Hepatocellular carcinoma (Childs-Pugh A or B7 only).
    • Colorectal cancer
    • Epithelial ovarian cancer
    • Cervical cancer
    • Endometrial adenocarcinoma
    • Thyroid cancer (follicular or papillary).
    Patients must have experienced progressive disease on or be intolerant to an established standard systemic anti-cancer therapy for a given tumor type or have been intolerant to such therapy, or have been considered ineligible for a particular form of standard therapy on medical grounds. Patients must have no available proven curative or life-prolonging therapies.
    4. For Cohort Expansion:
    a. Melanoma Cohort: histologically confirmed diagnosis of advanced and/or metastatic cutaneous melanoma in which radiological progression has been demonstrated during therapy with a PD-(L)1 immune CPI and for which no existing options are considered to provide clinical benefit (only one line of PD-(L)1 therapy is permitted). BRAF V600 mutation patients must have progressed on, or are intolerant to, BRAF +/- MEK inhibitor therapy.
    b. Colorectal Cohort: histologically confirmed diagnosis of advanced and/or metastatic colorectal adenocarcinoma. Patients must have had recurrence, progression or intolerance to standard therapy consisting of at least 2 prior standard regimens (containing a fluoropyrimidine plus a platinum analogue and/or irinotecan) for metastatic disease. Patients who are inappropriate candidates for or have refused treatment with these regimens are also eligible. Patients should have received no more than 4 prior regimens.
    c. Luminal or Triple Negative Breast Cancer: histologically confirmed diagnosis of advanced and/or metastatic luminal or triple negative breast cancer. Patient must have had recurrence, progression or intolerance to standard therapy consisting of at least 2 prior, but no more than 3 standard regimens for metastatic disease.
    d. Basket Cohort: patients with histologically diagnosed unresectable, locally advanced or metastatic tumor types eligible in Dose Escalation not listed in tumor specific expansion cohorts. Patients must have experienced progressive disease on an established standard systemic anti-cancer therapy for a given tumor type or have been intolerant to such therapy or have been considered ineligible for a particular form of standard therapy on medical grounds. Patients must have no available proven curative or life-prolonging therapies.
    5. Eastern Cooperative Oncology Group performance status ≤ 1.
    6. Life expectancy ≥12 weeks.
    7. Measurable disease as per RECIST 1.1 criteria and documented by CT and/or MRI
    8. Acceptable laboratory parameters:
    • Albumin ≥ 2.8 g/dL.
    • Platelet count ≥ 75,000.
    • Hemoglobin ≥ 8.0 g/dL.
    • Absolute neutrophil count ≥ 1,500/μL.
    • ALT/AST ≤ 3.0 times ULN.
    − ALT/AST ≤ 5 × ULN for patients with liver metastases.
    • Total bilirubin ≤ 1.5 ULN or ≤ 3 x ULN for patients with Gilbert’s disease.
    − Direct bilirubin ≤ ULN for patients with total bilirubin > 1.5 ULN.
    • Creatinine ≤ 1.8 mg/dL.
    − Or calculated/measured creatinine clearance > 30 mL/minute.
    9. Identification of an archival tumor sample.
    10. Consent to pre- and on- treatment fresh tumor biopsy for all patients enrolled as back fill in Dose Escalation or for at least 6 additional patients per expansion cohort in Cohort Expansion in Simon Stage 2.
    11. Female patients of childbearing potential must:
    • Have a negative serum or urine pregnancy test performed within 72 hours prior to the initiation of study drug administration.
    • Be willing to use 2 forms of effective contraception throughout the study. Abstinence is acceptable.
    12. Male patients with partners of childbearing potential, even if surgically sterilized must agree to:
    • Use effective barrier contraception from the time of consent through 90 days after discontinuation or agree to practice true abstinence.
    • Male patients should also have their partners use contraception for the same period of time.
    13. Central nervous system metastases must have been treated, be asymptomatic for ≥14 days and meet the following:
    • No concurrent treatment for CNS disease
    • No concurrent or past history of leptomeningeal disease or cord compression.
    14. Must be willing and able to comply with study clinic visits and procedures
    15. Concurrent use of hormones for breast cancer or for non-cancer-related conditions is acceptable. Bisphosphonates or RANK-L inhibitor or analogues are permitted.
    1. Edad ≥ 18 años.
    2. Consentimiento informado firmado
    3. Para el escalado de dosis, pacientes con diagnóstico histológico de tipos de tumores no resecables, localmente avanzados o metastásicos:
    - Cáncer de pulmón de células no pequeñas
    - Cáncer de pulmón de células pequeñas
    - Melanoma
    - Carcinoma renal de células claras o papilar
    - Cáncer urotelial
    - Cáncer de células escamosas de cabeza y cuello
    - Cáncer de mama luminal o triple negativo
    - Adenocarcinoma gástrico o gastroesofágico
    - Cáncer de células escamosas de esófago
    - Carcinoma de células escamosas de piel
    - Adenocarcinoma de páncreas
    - Carcinoma hepatocelular (sólo Childs-Pugh A o B7)
    - Cáncer colorrectal
    - Cáncer epitelial de ovario
    - Cáncer de cuello uterino
    - Adenocarcinoma de endometrio
    - Cáncer de tiroides (folicular o papilar).
    Los pacientes deben haber experimentado una enfermedad progresiva o ser intolerantes a una terapia anticancerosa sistémica estándar establecida o haber sido intolerantes/inelegibles a dicha terapia. Los pacientes deben carecer de terapias curativas o de prolongación de la vida probadas disponibles.
    4. Para la expansión de la cohorte:
    a. Cohorte de melanoma: diagnóstico histológicamente confirmado de melanoma cutáneo avanzado y/o metastásico en el que se haya demostrado la progresión radiológica durante la terapia con un IPC inmunológico PD-(L)1 y para el que no se considere que las opciones existentes proporcionen un beneficio clínico (sólo se permite una línea de terapia PD-(L)1). Los pacientes con mutación BRAF V600 deben haber progresado con la terapia de inhibidores BRAF +/- MEK o ser intolerantes a ella.
    b. Cohorte colorrectal: diagnóstico confirmado histológicamente de adenocarcinoma colorrectal avanzado y/o metastásico. Los pacientes deben haber tenido recurrencia, progresión o intolerancia a la terapia estándar consistente en al menos 2 regímenes estándar previos (que contengan una fluoropirimidina más un análogo del platino y/o irinotecán) para la enfermedad metastásica. Los pacientes no deben haber recibido más de 4 regímenes anteriores.
    c. Cáncer de mama luminal o triple negativo: diagnóstico confirmado histológicamente de cáncer de mama luminal o triple negativo avanzado y/o metastásico. La paciente debe haber tenido recurrencia, progresión o intolerancia a la terapia estándar consistente en al menos 2 regímenes anteriores, pero no más de 3, para la enfermedad metastásica.
    d. Cohorte de la cesta: pacientes con tipos de tumores histológicamente diagnosticados como no resecables, localmente avanzados o metastásicos, elegibles en la intensificación de la dosis y no incluidos en las cohortes de expansión específicas de los tumores. Los pacientes deben haber experimentado una enfermedad progresiva con una terapia estándar establecida o haber sido intolerantes/inelegibles a dicha terapia. Los pacientes deben carecer de terapias curativas o de prolongación de la vida probadas disponibles.
    5. Estado de rendimiento del Eastern Cooperative Oncology Group ≤ 1.
    6. Esperanza de vida ≥12 semanas.
    7. Enfermedad medible según los criterios RECIST 1.1 y documentada mediante TAC y/o RMN.
    8. Parámetros de laboratorio aceptables:
    - Albúmina ≥ 2,8 g/dL.
    - Recuento de plaquetas ≥ 75.000.
    - Hemoglobina ≥ 8,0 g/dL.
    - Recuento absoluto de neutrófilos ≥ 1.500/μL.
    - ALT/AST ≤ 3,0 veces el ULN.
    - ALT/AST ≤ 5 × ULN para pacientes con metástasis hepáticas.
    - Bilirrubina total ≤ 1,5 ULN o ≤ 3 x ULN para pacientes con enfermedad de Gilbert.
    - Bilirrubina directa ≤ ULN para pacientes con bilirrubina total > 1,5 ULN.
    - Creatinina ≤ 1,8 mg/dL.
    - O aclaramiento de creatinina calculado/medido > 30 mL/minuto.
    9. Identificación de una muestra tumoral de archivo.
    10. Consentimiento para la realización de una biopsia tumoral en fresco antes y durante el tratamiento para todos los pacientes inscritos como relleno en la Escalada de Dosis o para al menos 6 pacientes adicionales por cohorte de expansión en la Expansión de Cohortes en la Etapa 2 de Simon.
    11. Las pacientes en edad fértil deben:
    - Tener una prueba de embarazo negativa en suero u orina
    - Estar dispuestas a utilizar 2 formas de anticoncepción efectiva
    12. Los pacientes masculinos con parejas en edad fértil deben:
    - Utilizar métodos anticonceptivos de barrera eficaces desde el momento del consentimiento hasta 90 días después de la interrupción o practicar la abstinencia verdadera.
    - Hacer que sus parejas utilicen métodos anticonceptivos
    13. Las metástasis del SNC deben haber sido tratadas, estar asintomáticas durante ≥14 días y :
    - No tener tratamiento concurrente para la enfermedad del SNC
    - No tener historia concurrente o pasada de enfermedad leptomeníngea o compresión de la médula.
    14. Debe estar dispuesto y ser capaz de cumplir con las visitas y procedimientos clínicos del estudio
    15. Se acepta el uso concurrente de hormonas para el cáncer de mama o para condiciones no relacionadas con el cáncer.
    E.4Principal exclusion criteria
    1. Patients with symptomatic or unstable CNS primary tumor or metastases and/or carcinomatous meningitis. Patients with documented treated CNS metastases stable for at least 4 weeks may be enrolled at the discretion of the investigator.
    2. Patients with active, or history of, severe autoimmune disease who in the opinion of the investigator and/or the Sponsor or Sponsor’s designee would be exposed to unacceptable risk by participating in the study.
    3. Major surgery within 6 weeks from treatment initiation.
    4. Clinically significant cardiovascular/vascular disease ≤ 6 months before first dose:
    • Myocardial infarction or unstable angina.
    • Clinically significant cardiac arrhythmias.
    • Uncontrolled hypertension: systolic blood pressure (SBP) > 180 mmHg, diastolic blood pressure (DBP) > 100 mmHg.
    • Pulmonary embolism, symptomatic cerebrovascular events or any other serious cardiac condition (e.g., pericardial effusion or restrictive cardiomyopathy).
    • QTcF prolongation > 480 msec.
    • Congestive heart failure (New York Heart Association class III-IV).
    • Myocarditis/clinically significant pericarditis.
    5. Clinically significant gastrointestinal disorders including:
    • Gastrointestinal perforation or unhealed ulcerations < 6 months prior to study drug administration. Patients must have documented evidence (e.g., upper endoscopy, colonoscopy) of completely healed area of prior perforation.
    • Clinically significant gastrointestinal bleeding < 3 months prior to study drug administration.
    • Pancreatitis < 6 months prior to study drug administration.
    • History of Crohn’s disease or ulcerative colitis.
    6. Clinically significant pulmonary compromise requiring supplemental oxygen use.
    7. History of Grade 3 or greater drug-related immune-mediated AE during treatment with CPIs such as anti-PD-(L)1 or anti-CTLA-4 antibodies.
    8. Vaccination with any live virus vaccine within 4 weeks prior to the initiation of study drug administration. Inactivated annual influenza vaccination is allowed. At least 2 doses of COVID-19 vaccination must have been completed prior to enrollment.
    9. Known hypersensitivity to JK08 or any excipient (histidine/histidine-HCl, sucrose, glycine, PS-80).
    10. Second primary invasive malignancy not in remission for ≥ 1 year. Exceptions include non-melanoma skin cancer, cervical carcinoma in situ, resected melanoma in situ, or any malignancy considered to be indolent and never required therapy.
    11. Any serious underlying medical or psychiatric condition that would preclude understanding and rendering of informed consent or impair the ability of the patient to receive or tolerate the planned treatment.
    12. Recent or ongoing serious infection including:
    • Any uncontrolled Grade 3 or higher (per CTCAE v5.0) viral, bacterial, or fungal infection within 2 weeks prior to the first dose of JK08. Routine antimicrobial prophylaxis is allowed.
    • Uncontrolled infection with human immunodeficiency virus. Patients on stable highly active antiretroviral therapy (HAART) therapy with undetectable viral load and normal CD4 counts for at least 6 months prior to study entry are eligible. Serological testing for HIV at screening is not required.
    • Known to be positive for hepatitis B (HBV) surface antigen, or any other positive test for hepatitis B indicating acute or chronic infection. Patients who are or have received anti-HBV therapy and have undetectable HBV DNA for at least 6 months prior to study entry are eligible. Serological testing for hepatitis B at screening is not required.
    • Known active hepatitis C (HCV) as determined by positive serology and confirmed by polymerase chain reaction. Patients on or having received antiviral therapy are eligible provided they are virus-free by PCR for at least 6 months prior to study entry. Serological testing for hepatitis C at screening is not required.
    • Known active or latent tuberculosis.
    13. Use of systemic corticosteroids within 15 days or other immunosuppressive drugs within 30 days prior to start of the study, with the exception of corticosteroids as replacement therapy up to an equivalent of prednisone 10 mg/day which is allowed. Inhaled, topical, or intraarticular steroids are allowed.
    14. Prior systemic anti-cancer treatment as follows:
    • For cytotoxic chemotherapy, small molecule inhibitors, radiation, or similar investigational treatments, ≤ 2 weeks or 5 half-lives, whichever is shorter.
    • For monoclonal antibodies or similar experimental therapies: ≤ 3 weeks or 5 half-lives, whichever is shorter.
    • Antibody drug conjugates and radioimmunoconjugates or other similar experimental therapies ≤ 6 weeks or 5 half-lives, whichever is shorter.
    15. Ascites or pleural effusions requiring large volume para- or pleurocentesis within 4 weeks of treatment initiation.
    16. Pregnant or nursing.
    17. Therapeutic anticoagulation for a thromboembolic event that occurred within 3 months of dosing; prophylactic anticoagulation is permitted.
    1. Pacientes con tumor primario del SNC sintomático o inestable o con metástasis y/o meningitis carcinomatosa.
    2. Pacientes con enfermedad autoinmune activa, o con antecedentes de la misma.
    3. Cirugía mayor en las 6 semanas siguientes al inicio del tratamiento.
    4. Enfermedad cardiovascular/vascular clínicamente significativa ≤ 6 meses antes de la primera dosis:
    - Infarto de miocardio o angina inestable.
    - Arritmias cardíacas clínicamente significativas.
    - Hipertensión no controlada: presión arterial sistólica (PAS) > 180 mmHg, presión arterial diastólica (PAD) > 100 mmHg.
    - Embolia pulmonar, eventos cerebrovasculares sintomáticos o cualquier otra condición cardíaca grave
    - Prolongación del QTcF > 480 mseg.
    - Insuficiencia cardíaca congestiva (clase III-IV de la New York Heart Association).
    - Miocarditis/pericarditis clínicamente significativa.
    5. Trastornos gastrointestinales clínicamente significativos, incluyendo
    - Perforación gastrointestinal o ulceraciones no cicatrizadas < 6 meses antes de la administración del fármaco del estudio.
    - Hemorragia gastrointestinal clínicamente significativa < 3 meses antes de la administración del fármaco del estudio.
    - Pancreatitis < 6 meses antes de la administración del fármaco del estudio.
    - Antecedentes de enfermedad de Crohn o colitis ulcerosa.
    6. Compromiso pulmonar clínicamente significativo que requiera el uso de oxígeno suplementario.
    7. Antecedentes de EA inmunomediados relacionados con el fármaco de grado 3 o superior durante el tratamiento con IPC, como anticuerpos anti-PD-(L)1 o anti-CTLA-4.
    8. Vacunación con cualquier vacuna de virus vivos en las 4 semanas anteriores al inicio de la administración del fármaco del estudio. Al menos 2 dosis de la vacuna COVID-19 deben haberse completado antes de la inscripción.
    9. Hipersensibilidad conocida al JK08 o a cualquier excipiente.
    10. Segunda neoplasia invasiva primaria que no haya remitido durante ≥ 1 año. Las excepciones incluyen el cáncer de piel no melanoma, el carcinoma cervical in situ, el melanoma in situ resecado o cualquier malignidad considerada indolente y que nunca haya requerido terapia.
    11. Cualquier condición médica o psiquiátrica grave subyacente.
    12. Infección grave reciente o en curso, incluyendo:
    - Cualquier infección viral, bacteriana o fúngica no controlada de grado 3 o superior (según CTCAE v5.0) en las 2 semanas anteriores a la primera dosis de JK08. Se permite la profilaxis antimicrobiana de rutina.
    - Infección no controlada por el virus de la inmunodeficiencia humana. Son elegibles los pacientes en terapia antirretroviral altamente activa (HAART) estable con carga viral indetectable y recuentos normales de CD4 durante al menos 6 meses antes de la entrada en el estudio. No se requiere la prueba serológica del VIH en el momento del cribado.
    - Que se sepa que el antígeno de superficie de la hepatitis B (VHB) es positivo, o cualquier otra prueba positiva para la hepatitis B que indique una infección aguda o crónica. Son elegibles los pacientes que estén recibiendo o hayan recibido terapia contra el VHB y tengan un ADN del VHB indetectable durante al menos 6 meses antes de la entrada en el estudio. No se requiere una prueba serológica para la hepatitis B en el momento del cribado.
    - Hepatitis C (VHC) activa conocida, determinada por serología positiva y confirmada por reacción en cadena de la polimerasa. Los pacientes que estén recibiendo o hayan recibido terapia antiviral son elegibles siempre que estén libres del virus por PCR durante al menos 6 meses antes de la entrada en el estudio. No se requiere una prueba serológica para la hepatitis C en el momento del cribado.
    - Tuberculosis activa o latente conocida.
    13. Uso de corticosteroides sistémicos en los 15 días siguientes o de otros fármacos inmunosupresores en los 30 días anteriores al inicio del estudio, con la excepción de los corticosteroides como terapia de sustitución hasta un equivalente de prednisona de 10 mg/día, que está permitido. Se permiten los esteroides inhalados, tópicos o intraarticulares.
    14. Tratamiento anticanceroso sistémico previo, como se indica a continuación:
    - Para quimioterapia citotóxica, inhibidores de moléculas pequeñas, radiación o tratamientos similares en investigación, ≤ 2 semanas o 5 vidas medias, lo que sea más corto.
    - Para anticuerpos monoclonales o terapias experimentales similares: ≤ 3 semanas o 5 vidas medias, lo que sea más corto.
    - Conjugados anticuerpo-fármaco y radioinmunoconjugados u otras terapias experimentales similares ≤ 6 semanas o 5 vidas medias, lo que sea más corto.
    15. Ascitis o derrames pleurales que requieran para- o pleurocentesis de gran volumen en las 4 semanas siguientes al inicio del tratamiento.
    16. Embarazo o lactancia.
    17. Anticoagulación terapéutica por un acontecimiento tromboembólico ocurrido en los 3 meses siguientes a la administración de la dosis.
    E.5 End points
    E.5.1Primary end point(s)
    Primary endpoint:
    • MTD and/or DLT after one cycle of treatment and all SAEs, AEs tabulated/reported by type, grade, and frequency for the entire study duration.
    Objetivo principal:
    - MTD y/o DLT después de un ciclo de tratamiento y todos los SAE, AEs tabulados/reportados por tipo, grado y frecuencia para toda la duración del estudio.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Throughout the study
    Durante todo el estudio
    E.5.2Secondary end point(s)
    Secondary endpoint:
    • PK (analysis of Cmax, AUC, tmax, and t½ following treatment completion).
    • ADA status (see Section 10.3.8 for details of the reportable outcomes).
    • ORR according to standard RECIST 1.1 criteria.
    • DCR and PFS by RECIST 1.1 and OS in patients with advanced solid tumors.
    Objetivo secundario:
    - PK (análisis de Cmáx, AUC, tmáx y t½ tras la finalización del tratamiento).
    - Estado de la ADA (véase la sección 10.3.8 para los detalles de los resultados notificables).
    - ORR según los criterios estándar de RECIST 1.1.
    - RCD y SLP según RECIST 1.1 y SG en pacientes con tumores sólidos avanzados.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Throughout the study
    Durante todo el 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 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 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 concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA6
    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
    France
    Spain
    Belgium
    United Kingdom
    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 years3
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years3
    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: 68
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 69
    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 state20
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 120
    F.4.2.2In the whole clinical trial 137
    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)
    Expected normal treatment of that condition (SoC)
    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 Decision2022-11-03
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2022-09-09
    P. End of Trial
    P.End of Trial StatusOngoing
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