Un estudio de escalada de dosis de Fase I y de expansión de dosis para investigar la farmacocinética y la seguridad de durvalumab subcutáneo (IMFINZI-subQ)
Estudio de Fase I, multicéntrico, de escalada de dosis y expansión de dosis para investigar la farmacocinética y la seguridad de durvalumab subcutáneo en participantes adultos con tumores sólidos
The purpose of the study is to determine a subcutaneous (SC: under the skin) durvalumab + recombinant human hyaluronidase (rHu) dose that yields systemic drug exposure similar to intravenous (IV: into the veins) durvalumab administration and to evaluate the pharmacokinetics and safety of SC durvalumab + rHu injection in participants with different types of solid tumours (cancers).
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
This is a Phase I, multicentre study that will consist of 2 parts -
- Part 1: Dose Escalation
- Part 2: Dose Expansion
Part 1 may include participants with solid tumours - non-small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC) or limited-stage small cell lung cancer (LS-SCLC). It will further consist of 2 planned dose levels of SC durvalumab - Dose level 1 (DL1) and Dose level 2 (DL2).
Part 2 will include participants with unresectable HCC. It will be initiated once a dose has been identified based on Part 1.
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 1
Contactos y Ubicaciones
Estudio Contacto
- Nombre: AstraZeneca Clinical Study Information Center
- Número de teléfono: 1-877-240-9479
- Correo electrónico: information.center@astrazeneca.com
Ubicaciones de estudio
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Fitzroy, Australia, 3065
- Retirado
- Research Site
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St Albans, Australia, 3021
- Retirado
- Research Site
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Woolloongabba, Australia, 4102
- Retirado
- Research Site
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Seongnam-si, Corea del Sur, 13620
- Reclutamiento
- Research Site
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Seoul, Corea del Sur, 06351
- Reclutamiento
- Research Site
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Seoul, Corea del Sur, 5505
- Reclutamiento
- Research Site
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Seoul, Corea del Sur, 03722
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- Research Site
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Batumi, Georgia, 6010
- Reclutamiento
- Research Site
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Tbilisi, Georgia, 0114
- Reclutamiento
- Research Site
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Tbilisi, Georgia, 0112
- Reclutamiento
- Research Site
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Brzozów, Polonia, 36-200
- Reclutamiento
- Research Site
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Koszalin, Polonia, 75-581
- Reclutamiento
- Research Site
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Lublin, Polonia, 20-090
- Reclutamiento
- Research Site
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Olsztyn, Polonia, 10-357
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- Research Site
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Przemyśl, Polonia, 37-700
- Reclutamiento
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Tainan, Taiwán, 73657
- Reclutamiento
- Research Site
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Taipei, Taiwán, 112
- Retirado
- Research Site
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Taipei, Taiwán, 110
- Reclutamiento
- Research Site
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Taoyuan, Taiwán, 333
- Retirado
- Research Site
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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:
- An Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Life expectancy of ≥ 12 weeks at enrolment.
- Adequate organ and marrow function.
- Minimum body weight > 30 kg.
Part 1 only:
Locally Advanced Unresectable (Stage III) NSCLC Participants -
- Histological or cytological documented evidence of NSCLC (locally advanced, unresectable, Stage III).
- Must have received at least 2 cycles of platinum-based chemotherapy concurrent with definitive radiation therapy.
- Have not progressed following definitive concurrent chemoradiation.
LS-SCLC Participants -
- Histologically or cytologically documented LS-SCLC (Stage I-III).
- Received 4 cycles of chemotherapy concurrent with radiotherapy, which must be completed within 1 to 42 days prior to enrolment.
- Have not progressed following definitive concurrent chemoradiation.
Part 1 and 2:
Unresectable HCC Participants -
- Unresectable HCC based on histopathological confirmation.
- No prior systemic therapy for unresectable HCC.
- Must not be eligible for locoregional therapy for unresectable HCC.
- Child-Pugh Score class A.
- Measurable disease as defined by RECIST v1.1.
Exclusion Criteria:
- Active or prior documented autoimmune disease requiring systemic treatment.
- Uncontrolled infection (including human immunodeficiency virus [HIV], hepatitis B or C).
- Prior exposure to immune checkpoint inhibitors.
Part 1 only:
Locally Advanced Unresectable (Stage III) NSCLC Participants -
- Mixed SCLC and NSCLC histology.
- Active pneumonitis or interstitial lung disease requiring systemic therapy.
LS SCLC Participants -
- Mixed SCLC and NSCLC histology.
- Extensive-stage disease.
- History of Grade ≥ 2 pneumonitis.
Part 1 and 2:
Unresectable HCC Participants -
- Hepatic encephalopathy.
- Uncontrolled ascites.
- Active gastrointestinal (GI) bleeding.
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: Part 1: SC Durvalumab DL1
Participants will receive DL1 of SC durvalumab + rHu followed by IV durvalumab at predefined intervals. |
Durvalumab + rHu will be administered subcutaneously. Durvalumab will be administered intravenously.
Otros nombres:
Tremelimumab will be administered to participants with unresectable HCC as an IV infusion. |
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Experimental: Part 1: SC Durvalumab DL2
Participants will receive DL2 of SC durvalumab + rHu followed by IV durvalumab at predefined intervals. |
Durvalumab + rHu will be administered subcutaneously. Durvalumab will be administered intravenously.
Otros nombres:
Tremelimumab will be administered to participants with unresectable HCC as an IV infusion. |
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Experimental: Part 2: Expansion Cohort, SC Durvalumab Dose Level X
Participants will receive dose level X (determined from data analysis in Part 1) of SC durvalumab + rHu followed by IV durvalumab at predefined intervals. |
Durvalumab + rHu will be administered subcutaneously. Durvalumab will be administered intravenously.
Otros nombres:
Tremelimumab will be administered to participants with unresectable HCC as an IV infusion. |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Area under the concentration-time curve
Periodo de tiempo: From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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To characterise the AUC of SC durvalumab. |
From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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Observed lowest concentration before the next dose is administered (Ctrough)
Periodo de tiempo: From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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To characterise the Ctrough of SC durvalumab |
From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Area under the concentration-time curve from time 0 to last quantifiable concentration (AUClast)
Periodo de tiempo: From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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To characterise the AUClast of SC durvalumab. |
From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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Maximum observed concentration (Cmax)
Periodo de tiempo: From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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To characterise the Cmax of SC durvalumab. |
From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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Time to reach maximum concentration following drug administration (tmax)
Periodo de tiempo: From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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To characterise the tmax of SC durvalumab. |
From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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Terminal elimination half-life (t1/2λz)
Periodo de tiempo: From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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To characterise the t1/2λz of SC durvalumab. |
From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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Total body clearance/apparent total body clearance (CL[/F])
Periodo de tiempo: From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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To characterise the CL(/F) of SC durvalumab. |
From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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Apparent volume of distribution based on the terminal phase volume (Vz[/F])
Periodo de tiempo: From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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To characterise the VZ(/F) of SC durvalumab. |
From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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Average drug concentration over a dosing interval (Cavg)
Periodo de tiempo: From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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To characterise the Cavg of SC durvalumab. |
From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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Serum concentration of durvalumab
Periodo de tiempo: From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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To characterise the serum concentration of SC durvalumab at specified timepoints. |
From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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Number of participants with adverse events (AEs)
Periodo de tiempo: Up to Survival Follow-up (approximately 17 months)
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To assess the safety and tolerability of SC durvalumab. |
Up to Survival Follow-up (approximately 17 months)
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Number of participants with dose-limiting toxicities (DLTs)
Periodo de tiempo: Up to Survival Follow-up (approximately 17 months)
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To assess the safety and tolerability of SC durvalumab. |
Up to Survival Follow-up (approximately 17 months)
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Colaboradores e Investigadores
Patrocinador
Publicaciones y enlaces útiles
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
- Anticuerpo monoclonal
- Farmacocinética
- Subcutáneo
- Proteína de muerte celular programada 1
- Ligando de muerte celular programada 1 (PD-L1)
- Terapia anticancerígena
- Cáncer de pulmón de células no pequeñas (Estadio III, no resecable)
- Cáncer de pulmón de células pequeñas (estadio limitado)
- Carcinoma hepatocelular (No resecable)
- Hialuronidasa humana
Términos MeSH relevantes adicionales
- Neoplasias por sitio
- Neoplasias
- Enfermedades de las vías respiratorias
- Neoplasias por tipo histológico
- Neoplasias del Sistema Digestivo
- Enfermedades del Sistema Digestivo
- Enfermedades pulmonares
- Enfermedades del HIGADO
- Neoplasias Glandulares y Epiteliales
- Adenocarcinoma
- Neoplasias Hepaticas
- Neoplasias de las vías respiratorias
- Neoplasias torácicas
- Neoplasias Pulmonares
- Carcinoma
- Carcinoma Broncogénico
- Neoplasias Bronquiales
- Carcinoma Hepatocelular
- Carcinoma de pulmón de células no pequeñas
- Carcinoma de pulmón de células pequeñas
- durvalumab
- tremelimumab
Otros números de identificación del estudio
- D907HC00001
- 2025-521639-34-00 (Otro identificador: EU CT number)
- 2025 (Subvención/contrato del NIH de EE. UU.)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan IPD
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Marco de tiempo para compartir IPD
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Criterios de acceso compartido de IPD
When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
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.
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .