Study of IEV407 as Single Agent or in Combination in Patients With Advanced HR+/HER2- Breast Cancer
An Open-label, Multi-center, Phase I/Ib Study of IEV407 as a Single Agent and in Combination With Endocrine Therapy in Patients With Advanced Hormone Receptor Positive, HER2- Negative Breast Cancer
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
This is a first-in-human, open-label, phase I/Ib, multi-center study consisting of a dose escalation part of IEV407 as a single agent (SA) and in combination with endocrine therapy (fulvestrant or letrozole) followed by a dose expansion part in patients with advanced breast cancer (aBC). The study will start with the evaluation of IEV407 as a SA.
Following evaluation of IEV407 in combination with fulvestrant through dose escalation and establishment of a recommended dose and/or dose ranges for optimization (RD/DRO), the study may proceed to the Phase Ib expansion part to evaluate the combination treatment of IEV407 with fulvestrant. If more than one treatment arm is open concurrently in the dose expansion part, a randomization schedule will be employed for patient allocation.
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 1
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Novartis Pharmaceuticals
- Número de teléfono: 1-888-669-6682
- Correo electrónico: novartis.email@novartis.com
Copia de seguridad de contactos de estudio
- Nombre: Novartis Pharmaceuticals
- Número de teléfono: +41613241111
Ubicaciones de estudio
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Ontario
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Toronto, Ontario, Canadá, M5G 2M9
- Reclutamiento
- Novartis Investigative Site
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Seoul
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Seoul, Seoul, Corea del Sur, 06351
- Reclutamiento
- Novartis Investigative Site
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Connecticut
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New Haven, Connecticut, Estados Unidos, 06520
- Reclutamiento
- Yale New Haven Hospital
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Contacto:
- Carl Brown
- Correo electrónico: carl.brown@yale.edu
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Investigador principal:
- Jing Du
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Texas
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Dallas, Texas, Estados Unidos, 75251
- Reclutamiento
- Mary Crowley Cancer Research
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Investigador principal:
- Reva Schneider
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Contacto:
- Pramitha Kondancheri
- Número de teléfono: +1 972 566 3000
- Correo electrónico: Pramitha.RarothKondancheri@scri.com
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Osaka
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Hirakata, Osaka, Japón, 5731191
- Reclutamiento
- Novartis Investigative Site
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Singapore, Singapur, 119074
- Reclutamiento
- Novartis Investigative Site
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Descripción
Inclusion Criteria:
- Age ≥ 18 years old
Patients with one of the following indications:
- Dose escalation (IEV407 single agent and in combination with fulvestrant or letrozole):
HR+/HER2- aBC with disease progression on or following, or have been intolerant to, at least one line of endocrine-based therapy in combination with a CDK4/6 inhibitor and at least one additional line of systemic therapy in the unresectable/metastatic setting and not be a candidate for any available standard therapy, in the investigator's judgement.
- Dose expansion of IEV407 in combination with fulvestrant: HR+/HER2- aBC with disease progression on or following, or have been intolerant to, endocrine-based therapy in combination with a CDK4/6 inhibitor. They must not have received more than two prior lines of endocrine-based therapy in the unresectable/metastatic setting. Prior cytotoxic chemotherapy and/or antibody-drug conjugate therapies in the unresectable/metastatic setting are not allowed.
Exclusion Criteria:
- Patients with inadequate bone marrow and/or organ functions with out-of-range laboratory values.
- Impaired cardiac function or clinically significant cardiac disease.
- Concurrent use of hormone replacement therapy.
- Women of childbearing potential who are unwilling to use highly effective contraception methods, pregnant or nursing women.
- For the combination treatment of IEV407 with fulvestrant or letrozole: Patients with symptomatic visceral disease or any disease burden that makes the patient ineligible for endocrine-based therapy.
Other protocol-defined inclusion/exclusion criteria may apply.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación Secuencial
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Experimental: Dose escalation: IEV407 single agent
IEV407 single agent
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Oral administration
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Experimental: Dose escalation: IEV407 + fulvestrant
IEV407 in combination with fulvestrant
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Intramuscular injection.
Approved medication.
Otros nombres:
Oral administration
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Experimental: Dose escalation: IEV407 + letrozole
IEV407 in combination with letrozole
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Oral administration.
Approved medication.
Otros nombres:
Oral administration
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Experimental: Dose expansion, recommended dose (RD)-1: IEV407 + fulvestrant
IEV407 in combination with fulvestrant
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Intramuscular injection.
Approved medication.
Otros nombres:
Oral administration
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Experimental: Dose expansion, RD-2 (optional dose optimization): IEV407 + fulvestrant
IEV407 in combination with fulvestrant
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Intramuscular injection.
Approved medication.
Otros nombres:
Oral administration
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Incidence and severity of dose-limiting toxicities (DLTs)
Periodo de tiempo: 28 days
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Number of participants with DLTs.
A DLT is defined as an adverse event or abnormal laboratory value of Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or higher, including death, unless clearly and incontrovertibly assessed as due to disease, disease progression, inter-current illness/injury, concomitant medications, or extraneous causes, that occurs within the first 28 days of treatment with IEV407 in the dose escalation parts or in the expansion part of IEV407 in combination with fulvestrant with the exceptions described in the study protocol.
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28 days
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Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Periodo de tiempo: Up to approximately 2 years
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Number of participants with AEs and SAEs, including changes in laboratory values, vital signs and echocardiograms (ECGs) qualifying and reported as AEs.
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Up to approximately 2 years
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Frequency of dose interruptions, reductions and discontinuations
Periodo de tiempo: Up to approximately 2 years
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Number of participants with dose adjustments (interruptions, reductions, or permanent discontinuation) as a measure of tolerability.
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Up to approximately 2 years
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Dose intensity
Periodo de tiempo: Up to approximately 2 years
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Dose intensity defined as the ratio of actual cumulative dose received and actual duration of exposure.
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Up to approximately 2 years
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Best Overall Response (BOR)
Periodo de tiempo: Up to approximately 2 years
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BOR per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) is defined as the best overall confirmed response recorded from the start of the treatment until progressive disease (PD), death, start of new therapy, withdrawal of consent or end of study, whatever comes first.
Efficacy will be based on the investigator assessment.
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Up to approximately 2 years
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Overall Response Rate (ORR)
Periodo de tiempo: Up to approximately 2 years
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ORR per RECIST v1.1 is defined as the proportion of patients with a BOR of Complete response (CR) or Partial response (PR). Efficacy will be based on the investigator assessment. |
Up to approximately 2 years
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Disease Control Rate (DCR)
Periodo de tiempo: Up to approximately 2 years
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DCR per RECIST v1.1 is defined as the proportion of patients with a BOR of CR, PR, or Stable Disease (SD). Efficacy will be based on the investigator assessment. |
Up to approximately 2 years
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Clinical Benefit Rate (CBR)
Periodo de tiempo: Up to approximately 2 years
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CBR per RECIST v1.1 is defined as the proportion of patients with a BOR of CR, PR, or an overall lesion response of SD or Non-CR/Non-PD which lasts for at least 24 weeks. Efficacy will be based on the investigator assessment. |
Up to approximately 2 years
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Duration of Response (DOR)
Periodo de tiempo: Up to approximately 2 years
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DOR per RECIST v1.1 is the time between the first documented response (CR or PR) and the date of progression by local review as applicable or death due to any cause. Efficacy will be based on the investigator assessment. |
Up to approximately 2 years
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Progression Free Survival (PFS)
Periodo de tiempo: Up to approximately 2 years
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PFS per RECIST 1.1 is defined as the time from the date of start of study treatment (Phase I) or the date of randomization (Phase II) to the date of the first documented progression or death due to any cause. Efficacy will be based on the investigator assessment. |
Up to approximately 2 years
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Maximum plasma concentration (Cmax) of IEV407
Periodo de tiempo: From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. 1 cycle = 28 days
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Pharmacokinetic (PK) parameters based on plasma concentrations of IEV407.
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From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. 1 cycle = 28 days
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Area under the plasma concentration-time curve (AUC) of IEV407
Periodo de tiempo: From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. 1 cycle = 28 days
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PK parameters based on plasma concentrations of IEV407.
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From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. 1 cycle = 28 days
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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
Palabras clave
Términos MeSH relevantes adicionales
- Hormonas
- Hormonas, sustitutos hormonales y antagonistas hormonales
- Químicos orgánicos
- Compuestos heterocíclicos, 1 anillo
- Compuestos heterocíclicos
- Azoles
- Compuestos policíclicos
- Esteroides
- Compuestos de anillo fusionado
- Nitrilos
- Estradiol
- Estreness
- Estranos
- Congéneres de estradiol
- Hormonas esteroides gonadal
- Hormonas gonadales
- Triazoles
- Letrozol
- Fulvestrant
Otros números de identificación del estudio
- CIEV407A12101
- 2025 (Subvención/contrato del NIH de EE. UU.: Faculty of Social Sciences Scientific Grant at the University of Gdańsk)
- 2025-522707-26 (Identificador de registro: EU CTIS)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan IPD
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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