Un estudio para probar diferentes dosis de BI 764532 en pacientes con cáncer de pulmón de células pequeñas y otros tumores neuroendocrinos que son positivos para el ligando tipo delta 3 (DLL3).
Un primer ensayo de fase I en humanos, no aleatorizado, abierto, multicéntrico de aumento de dosis de BI 764532 administrado mediante infusiones intravenosas repetidas en pacientes con carcinoma de pulmón de células pequeñas y otras neoplasias neuroendocrinas que expresan DLL3
This study is open to adults with small cell lung cancer and other neuroendocrine cancers that are positive for the tumour marker delta-like 3 (DLL3). The study is in people with advanced cancer for whom previous treatment was not successful or no standard treatment exists.
The purpose of this study is to find out the highest dose of obrixtamig and the best treatment schedule that people can tolerate. Obrixtamig is an antibody-like molecule (DLL3/CD3 bispecific) that may help the immune system fight cancer. In this study, obrixtamig is given to people for the first time. Interim clinical data are available for obrixtamig.
Participants get obrixtamig either weekly or once every 3 weeks. If there is benefit for the participants and if they can tolerate it, the treatment is given for a maximum of 3 years. During this time, participants visit the study site about 20 times depending on the response to the treatment. Doctors record any unwanted effects and regularly check the general health of the participants.
Descripción general del estudio
Estado
Estado
Condiciones
Condiciones
Intervención / Tratamiento
Intervención / Tratamiento
Tipo de estudio
Tipo de estudio
Inscripción (Actual)
Inscripción
Fase
Fase
- Fase 1
Contactos y Ubicaciones
Ubicaciones de estudio
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Cologne, Alemania, 50937
- Universitätsklinikum Köln (AöR)
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Dresden, Alemania, 01307
- Technische Universität Dresden
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Würzburg, Alemania, 97078
- Universitätsklinikum Würzburg AÖR
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Barcelona, España, 08035
- Hospital Universitari Vall d'Hebron
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Barcelona, España, 08003
- Hospital del Mar
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Pamplona, España, 31008
- Clínica Universidad de Navarra
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Valencia, España, 46010
- Hospital Clinico Universitario de Valencia
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Georgia
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Atlanta, Georgia, Estados Unidos, 30322
- Winship Cancer Institute
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Maryland
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Baltimore, Maryland, Estados Unidos, 21201
- University of Maryland School of Medicine
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Missouri
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St Louis, Missouri, Estados Unidos, 63108
- Washington University School of Medicine
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Pennsylvania
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Pittsburgh, Pennsylvania, Estados Unidos, 15232
- University of Pittsburgh Medical Center
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Chiba, Kashiwa, Japón, 277-8577
- National Cancer Center Hospital East
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Criterios de participación
Criterio de elegibilidad
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
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Signed and dated, written informed consent form (ICF2, ICF3 or ICF4) in accordance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) - Good Clinical Practice (GCP) and local legislation prior to any trial-specific procedures, sampling, or analyses.
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Locally advanced or metastatic cancer not amenable to curative treatment; of following histologies:
- Small cell lung carcinoma (SCLC)
- Large cells neuroendocrine lung carcinoma (LCNEC)
- Neuroendocrine carcinoma (NEC) or small cell carcinoma of any other origin
- Tumours must be positive for DLL3 expression (on archived tissue or instudy fresh biopsy) according to central pathology review in order to start obrixtamig
- Patients with tumours with mixed histologies for any above type are eligible only if neuroendocrine carcinoma/small tumor cells component is predominant and represent at least 50% of the overall tumour tissue.
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For back-fill cohorts only: patient has agreed to and signed an IC to provide mandatory pre-treatment and on-treatment fresh tumor biopsy.
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Patient has failed or is not eligible for available standard therapies according to local guidelines. Standard therapies should include at least one line of chemotherapy that should include platinum for patients with small cells carcinoma tumors histologies.
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Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
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At least one evaluable lesion outside of CNS as defined per modified Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.
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Subjects with brain metastases are eligible provided they meet the following criteria:
- Radiotherapy or surgery for brain metastases was completed at least 2 weeks prior to the first administration of obrixtamig
- Patient is off steroids for at least 7 days (physiologic doses of steroids are permitted), and the patient is off anti-epileptic drugs for at least 7 days or on stable doses of anti-epileptic drugs for malignant Central Nervous System (CNS) disease.
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Adequate liver, bone marrow and renal organ function. Further inclusion criteria apply.
Exclusion Criteria:
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Previous treatment with T cell Engager (TcE) or cell therapies targeting DLL3. Other DLL3 targeting agents (like Rovalpituzumab tesirine (RovaT)) are allowed only if DLL3 positivity is documented after completion of treatment with DLL3 targeting agent in post-treatment biopsy.
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Anticoagulant treatment that cannot be safely interrupted based on opinion of the investigator if medically needed (e.g. biopsy).
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Persistent toxicity from previous treatments that has not resolved to = Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 (except for alopecia, CTCAE Grade 2 neuropathy, asthenia/fatigue or grade 2 endocrinopathies controlled by replacement therapy).
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Patient has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of obrixtamig. Physiological replacement of steroids is allowed.
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Prior anti-cancer therapy:
- Patients who have been treated with any other anti-cancer drug within 3 weeks or within 5 half-life periods (whichever is shorter) prior to first administration of obrixtamig.
- Patients who have been treated with extensive field radiotherapy including whole brain irradiation within 2 weeks prior to first administration of obrixtamig.
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Other active malignancy that could interfere with the prognosis and treatment of the disease of the study.
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Major surgery within 28 days of first dose obrixtamig.
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Women who are pregnant (including those who are considered to be possibly pregnant based on the investigator's clinical judgement), nursing/breast feeding or who plan to become pregnant or nurse while in the trial or within 60 days after the last dose of study treatment.
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Presence of any infection requiring systemic antimicrobial treatment within 7 days prior to first dose of trial medication. Patients who have any clinical signs of infection within 48 h prior to first dose of trial medication are not eligible.
Further exclusion criteria apply.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: No aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Número de brazos
Armas e Intervenciones
Grupo de participantes/brazoGrupo de participantes/brazo |
Intervención / TratamientoIntervención / Tratamiento |
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Experimental: Arm 1: Obrixtamig
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Obrixtamig - parenteral 1
Otros nombres:
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Experimental: Arm 2: Obrixtamig
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Obrixtamig - parenteral 2
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Grupo 1 y Grupo 2: Número de pacientes con DLT en el período de evaluación de MTD
Periodo de tiempo: hasta 36 meses
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hasta 36 meses
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Arm 1 and Arm 2: Maximum tolerated dose (MTD)
Periodo de tiempo: up to 36 months
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Maximum tolerated dose (MTD) in any studied regimen defined as the highest dose with less than 25% risk of the true Dose Limiting Toxicity (DLT) rate being equal or above 33% during the MTD evaluation period. Separate MTDs will be determined for each Regimen. |
up to 36 months
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Medidas de resultado secundarias
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Grupo 1 y Grupo 2: Área bajo la curva concentración-tiempo (AUCτ) del analito durante un intervalo de dosificación uniforme τ
Periodo de tiempo: hasta 36 meses
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hasta 36 meses
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Arm 1 and Arm 2: Maximum measured concentration (Cmax) of obrixtamig
Periodo de tiempo: up to 36 months
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up to 36 months
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Arm 1 and Arm 2: Objective response based on RECIST 1.1 criteria in patients with measurable disease
Periodo de tiempo: up to 36 months
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Objective response based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria in patients with measurable disease |
up to 36 months
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Colaboradores e Investigadores
Patrocinador
Patrocinador
Publicaciones y enlaces útiles
Enlaces Útiles
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Inicio del estudio
Finalización primaria (Actual)
Finalización primaria
Finalización del estudio (Estimado)
Finalización del estudio
Fechas de registro del estudio
Enviado por primera vez
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Publicado por primera vez
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización publicada
Última actualización enviada que cumplió con los criterios de control de calidad
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
Otros números de identificación del estudio
- 1438-0001
- 2019-000729-31 (Identificador de registro: EudraCT Number)
- 2024-513100-34-00 (Identificador de registro: CTIS)
- 2019 (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
Once the criteria in section 'time frame' are fulfilled, researchers can use the following link https://www.clinicalstudies.boehringer-ingelheim.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement". Furthermore, researchers can request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.
Marco de tiempo para compartir IPD
One year after the approval has been granted by major Regulatory Authorities and after the primary manuscript has been accepted for publication, or after termination of the development program.
Criterios de acceso compartido de IPD
For study documents -upon signing of a 'Document Sharing Agreement'.For study data -1. after the submission and approval of the research proposal (checks will be performed by the sponsor and/or the independent review panel, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a legal agreement.
Tipo de información de apoyo para compartir IPD
- PROTOCOLO DE ESTUDIO
- SAVIA
- RSC
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. .