Un estudio de ITC-6146RO en pacientes con cáncer avanzado o metastásico que han fracasado con la terapia estándar
Un estudio de fase 1a/b, de etiqueta abierta, multicéntrico, primero en humanos, de escalada de dosis/expansión con múltiples cohortes para evaluar la seguridad, tolerabilidad, farmacocinética y la eficacia antitumoral preliminar de ITC-6146RO en pacientes con cáncer avanzado o metastásico que han fallado a la terapia estándar
The study consists of Phase 1a (dose escalation) and Phase 1b (dose expansion). In Phase 1a, sequential cohorts of subjects will receive escalating doses of ITC-6146RO to determine maximum tolerated dose (MTD) and/or optimal biological dose (OBD).
In Phase 1b, the recommended phase 2 dose (RP2D) chosen from Phase 1a will be evaluated to further investigate safety, tolerability, pharmacokinetic (PK) and anti-tumor efficacy of ITC-6146RO.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 1
Contactos y Ubicaciones
Ubicaciones de estudio
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Seoul
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Seoul, Seoul, Corea del Sur, 05505
- Asan Medical Center
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Seoul, Seoul, Corea del Sur, 06351
- Samsung Medical Center
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Seoul, Seoul, Corea del Sur, 03722
- Severance Hospital
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-
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- Adult males and females aged ≥ 19 years (Korea) or ≥ 18 years (United States)
- Patients must be individuals who have voluntarily agreed to participate in the study after receiving a detailed explanation and fully understanding the nature of the clinical trial, and who have provided written informed consent.
- Pathological confirmation of malignancy and evidence of metastatic or surgically unresectable disease
- Patients must have at least one evaluable or measurable lesion based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST version 1.1). However, for patients with prostate cancer, eligibility will be determined based on Prostate Cancer Working Group 3 (PCWG3)
- Patients who have received standard therapies and have no remaining clinically available approved treatment options.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Estimated life expectancy of ≥ 3 months
Exclusion Criteria:
- Inability to comply with study and follow-up procedures
- Patients with a prior history of anticancer therapy before the first dose
- History of another active malignancy within the past 3 years
- Patients with central nervous system metastases, leptomeningeal disease, or spinal cord compression.
- Patients who are currently participating in a clinical trial or have participated in a clinical trial involving a medical device or investigational product within 28 days prior to the first administration of ITC-6146RO
- Has prior treatment with duocarmycin-containing agents
- Pregnancy, lactation, or breastfeeding
- Known Human immunodeficiency virus (HIV), Hepatitis C virus (HCV) and Hepatitis B virus (HBV) infection with active disease exception of the following conditions.
- Tuberculosis with active disease
- Active infection necessitating systemic therapy
- Prior allogenic bone marrow transplantation or solid organ transplantation
- History of autoimmune disease, treatment with systemic immunosuppressive medications
- Patients with clinically significant pulmonary disease
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: N / A
- Modelo Intervencionista: Asignación Secuencial
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Experimental: Phase 1a/b
The study consists of a Phase 1a dose-escalation part and a Phase 1b dose-expansion part. |
ITC-6146RO will be administered as an intravenous (IV) infusion at protocol-specified dose levels and schedules in Phase 1a (dose escalation) and Phase 1b (dose expansion). |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Phase 1a (Dose Escalation) Incidence of Adverse Events (AEs)
Periodo de tiempo: Through study completion (Up to 2 years)
|
Grade 3 and 4 AEs, Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Dose-limiting toxicities (DLTs) and AEs leading to discontinuation of study treatment, Evaluation of all-grade cardiac, renal, and pulmonary AEs , n, (%) |
Through study completion (Up to 2 years)
|
|
Phase 1b (Dose Expansion) Incidence of AEs
Periodo de tiempo: Through study completion (Up to 2 years)
|
Grade 3 and 4 AEs, TEAEs, SAEs and AEs leading to discontinuation of study treatment, Evaluation of all-grade cardiac, renal, and pulmonary AEs, n, % |
Through study completion (Up to 2 years)
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Phase 1a (Dose Escalation) Maximum Tolerated Dose (MTD) or Optimal Biological Dose (OBD) of ITC-6146RO
Periodo de tiempo: Through study completion (Up to 2 years)
|
MTD/OBD will be reported as the final selected dose level for further investigation from Phase 1a dose escalation. MTD is determined by DLTs observed during the prespecified DLT observation period, and OBD is determined by meeting prespecified biological activity criteria (as defined in the protocol). |
Through study completion (Up to 2 years)
|
|
Phase 1a (Dose Escalation) Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) After Single-Dose Administration of ITC-6146RO
Periodo de tiempo: Through study completion (Up to 2 years)
|
Plasma AUClast following a single dose of ITC-6146RO will be calculated from plasma concentration-time data and summarized descriptively. |
Through study completion (Up to 2 years)
|
|
Phase 1a (Dose Escalation) Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUCinf) After Single-Dose Administration of ITC-6146RO
Periodo de tiempo: Through study completion (Up to 2 years)
|
Plasma AUCinf following a single dose of ITC-6146RO will be calculated from plasma concentration-time data and summarized descriptively. |
Through study completion (Up to 2 years)
|
|
Phase 1a (Dose Escalation) Maximum Observed Plasma Concentration (Cmax) After Single-Dose Administration of ITC-6146RO
Periodo de tiempo: Through study completion (Up to 2 years)
|
Plasma Cmax following a single dose of ITC-6146RO will be calculated from plasma concentration-time data and summarized descriptively. |
Through study completion (Up to 2 years)
|
|
Phase 1a (Dose Escalation) Terminal Elimination Half-life (t1/2) After Single-Dose Administration of ITC-6146RO
Periodo de tiempo: Through study completion (Up to 2 years)
|
Plasma terminal elimination half-life (t1/2) following a single dose of ITC-6146RO will be calculated from plasma concentration-time data and summarized descriptively. |
Through study completion (Up to 2 years)
|
|
Phase 1a (Dose Escalation) Time to Maximum Observed Plasma Concentration (Tmax) After Single-Dose Administration of ITC-6146RO
Periodo de tiempo: Through study completion (Up to 2 years)
|
Plasma Tmax following a single dose of ITC-6146RO will be calculated from plasma concentration-time data and summarized descriptively. |
Through study completion (Up to 2 years)
|
|
Phase 1a (Dose Escalation) Apparent Clearance (CL) After Single-Dose Administration of ITC-6146RO
Periodo de tiempo: Through study completion (Up to 2 years)
|
Plasma apparent clearance (CL) following a single dose of ITC-6146RO will be calculated from plasma concentration-time data and summarized descriptively. |
Through study completion (Up to 2 years)
|
|
Phase 1a (Dose Escalation) Apparent Volume of Distribution (Vz) After Single-Dose Administration of ITC-6146RO
Periodo de tiempo: Through study completion (Up to 2 years)
|
Plasma apparent volume of distribution (Vz) following a single dose of ITC-6146RO will be calculated from plasma concentration-time data and summarized descriptively. |
Through study completion (Up to 2 years)
|
|
Phase 1a (Dose Escalation) Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) After Multiple-Dose Administration of ITC-6146RO
Periodo de tiempo: Through study completion (Up to 2 years)
|
Plasma AUClast following multiple-dose administration of ITC-6146RO will be calculated from plasma concentration-time data and summarized descriptively. |
Through study completion (Up to 2 years)
|
|
Phase 1a (Dose Escalation) Maximum Observed Plasma Concentration at Steady State (Cmax,ss) After Multiple-Dose Administration of ITC-6146RO
Periodo de tiempo: Through study completion (Up to 2 years)
|
Plasma Cmax,ss (as applicable) following multiple-dose administration of ITC-6146RO will be calculated from plasma concentration-time data and summarized descriptively. |
Through study completion (Up to 2 years)
|
|
Phase 1a (Dose Escalation) Trough Plasma Concentration at Steady State (Ctrough,ss) After Multiple-Dose Administration of ITC-6146RO
Periodo de tiempo: Through study completion (Up to 2 years)
|
Plasma Ctrough,ss (as applicable) following multiple-dose administration of ITC-6146RO will be calculated from plasma concentration-time data and summarized descriptively. |
Through study completion (Up to 2 years)
|
|
Phase 1a (Dose Escalation) Average Plasma Concentration Over the Dosing Interval at Steady State (Cav,τ) After Multiple-Dose Administration of ITC-6146RO
Periodo de tiempo: Through study completion (Up to 2 years)
|
Plasma Cav,τ (as applicable) following multiple-dose administration of ITC-6146RO will be calculated from plasma concentration-time data and summarized descriptively. |
Through study completion (Up to 2 years)
|
|
Phase 1a (Dose Escalation) Terminal Elimination Half-life at Steady State (t1/2,ss) After Multiple-Dose Administration of ITC-6146RO
Periodo de tiempo: Through study completion (Up to 2 years)
|
Plasma terminal elimination half-life at steady state (t1/2,ss) (as applicable) following multiple-dose administration of ITC-6146RO will be calculated from plasma concentration-time data and summarized descriptively. |
Through study completion (Up to 2 years)
|
|
Phase 1a (Dose Escalation) Time to Maximum Observed Plasma Concentration at Steady State (Tmax,ss) After Multiple-Dose Administration of ITC-6146RO
Periodo de tiempo: Through study completion (Up to 2 years)
|
Plasma Tmax,ss (as applicable) following multiple-dose administration of ITC-6146RO will be calculated from plasma concentration-time data and summarized descriptively. |
Through study completion (Up to 2 years)
|
|
Phase 1a (Dose Escalation) Apparent Clearance at Steady State (CLss) After Multiple-Dose Administration of ITC-6146RO
Periodo de tiempo: Through study completion (Up to 2 years)
|
Plasma apparent clearance at steady state (CLss) (as applicable) following multiple-dose administration of ITC-6146RO will be calculated from plasma concentration-time data and summarized descriptively. |
Through study completion (Up to 2 years)
|
|
Phase 1a (Dose Escalation) Apparent Volume of Distribution at Steady State (Vss) After Multiple-Dose Administration of ITC-6146RO
Periodo de tiempo: Through study completion (Up to 2 years)
|
Plasma apparent volume of distribution at steady state (Vss) (as applicable) following multiple-dose administration of ITC-6146RO will be calculated from plasma concentration-time data and summarized descriptively. |
Through study completion (Up to 2 years)
|
|
Phase 1a (Dose Escalation) Accumulation Ratio After Multiple-Dose Administration of ITC-6146RO
Periodo de tiempo: Through study completion (Up to 2 years)
|
Accumulation ratio (as applicable) following multiple-dose administration of ITC-6146RO will be calculated from plasma concentration-time data and summarized descriptively. |
Through study completion (Up to 2 years)
|
|
Phase 1a (Dose Escalation) Peak-to-Trough Fluctuation (PTF) After Multiple-Dose Administration of ITC-6146RO
Periodo de tiempo: Through study completion (Up to 2 years)
|
Peak-to-trough fluctuation (PTF) (as applicable) following multiple-dose administration of ITC-6146RO will be calculated from plasma concentration-time data and summarized descriptively. |
Through study completion (Up to 2 years)
|
|
Phase 1a (Dose Escalation) Incidence of Anti-Drug Antibodies (ADAs) to ITC-6146RO
Periodo de tiempo: Through study completion (Up to 2 years)
|
Percentage of participants with detectable ADAs to ITC-6146RO (ADA-positive) based on a validated immunoassay. |
Through study completion (Up to 2 years)
|
|
Phase 1b (Dose Expansion) Population Pharmacokinetic (PopPK) Parameters of ITC-6146RO
Periodo de tiempo: Through study completion (Up to 2 years)
|
PopPK parameters (e.g.,clearance and volume of distribution) will be estimated using PopPK modeling based on measured ITC-6146RO concentrations. |
Through study completion (Up to 2 years)
|
|
Phase 1b (Dose Expansion) Incidence of Anti-Drug Antibodies (ADAs) and Neutralizing Antibodies (NAbs) to ITC-6146RO
Periodo de tiempo: Through study completion (Up to 2 years)
|
Percentage of participants with detectable ADAs, including NAbs, to ITC-6146RO, as determined by validated immunoassay and neutralization assays (as applicable). |
Through study completion (Up to 2 years)
|
|
Phase 1a/b (Dose Escalation, Dose Expansion) Objective Response Rate (ORR) by Investigator per RECIST v1.1
Periodo de tiempo: Through study completion (Up to 2 years)
|
ORR will be assessed by the investigator per RECIST v1.1 |
Through study completion (Up to 2 years)
|
|
Phase 1a/b (Dose Escalation, Dose Expansion) Duration of Response (DoR) by Investigator per RECIST v1.1
Periodo de tiempo: Through study completion (Up to 2 years)
|
DoR will be assessed by the investigator per RECIST v1.1 |
Through study completion (Up to 2 years)
|
|
Phase 1a/b (Dose Escalation, Dose Expansion) Time to Response (TTR) by Investigator per RECIST v1.1
Periodo de tiempo: Through study completion (Up to 2 years)
|
TTR will be assessed by the investigator per RECIST v1.1 |
Through study completion (Up to 2 years)
|
|
Phase 1a/b (Dose Escalation, Dose Expansion) Progression-Free Survival (PFS) by Investigator per RECIST v1.1
Periodo de tiempo: Through study completion (Up to 2 years)
|
PFS will be assessed by the investigator per RECIST v1.1 |
Through study completion (Up to 2 years)
|
Otras medidas de resultado
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Phase 1b (Dose Expansion) Association Between ITC-6146RO Pharmacokinetic Parameters and Efficacy and Safety Endpoints
Periodo de tiempo: Through study completion (Up to 2 years)
|
Correlation between ITC-6146RO pharmacokinetic (PK) parameters and selected efficacy, safety, and exploratory endpoints. Efficacy endpoints may include objective response rate (ORR) and progression-free survival (PFS). Associations will be evaluated using appropriate exposure-response analyses. |
Through study completion (Up to 2 years)
|
|
Phase 1a/b (Dose Escalation, Dose Expansion) Overall Survival (OS)
Periodo de tiempo: Through study completion (Up to 2 years)
|
OS is defined as the time from randomization until death from any cause. |
Through study completion (Up to 2 years)
|
|
Phase 1a/b (Dose Escalation, Dose Expansion) Association Between B7-H3 Expression in Tumor Tissue and Anti-Tumor Efficacy
Periodo de tiempo: Through study completion (Up to 2 years)
|
Correlation between B7-H3 expression in tumor tissue assessed by immunohistochemistry (IHC) and anti-tumor efficacy endpoints, including objective response rate (ORR) and progression-free survival (PFS). ORR is defined as the proportion of participants with confirmed complete or partial response, and PFS as time to disease progression or death per protocol-defined criteria. Associations will be evaluated using appropriate statistical methods. In participants with metastatic castration-resistant prostate cancer (mCRPC), PSA response rate (≥50% decline from baseline) and time to PSA progression will also be assessed. |
Through study completion (Up to 2 years)
|
Colaboradores e Investigadores
Patrocinador
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
- Procesos Patológicos
- Neoplasias por sitio
- Neoplasias
- Enfermedades de las vías respiratorias
- Enfermedades pulmonares
- Neoplasias de las vías respiratorias
- Neoplasias torácicas
- Procesos Neoplásicos
- Neoplasias Pulmonares
- Enfermedades de la piel
- Enfermedades de los senos
- Carcinoma Broncogénico
- Neoplasias Bronquiales
- Neoplasias de mama
- Condiciones Patológicas, Signos y Síntomas
- Enfermedades de la piel y del tejido conectivo
- Metástasis de neoplasias
- Carcinoma de pulmón de células no pequeñas
- Neoplasias mamarias triple negativas
Otros números de identificación del estudio
- ITC06P1-P01
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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