Sym022 (Anti-LAG-3) in Patients With Advanced Solid Tumor Malignancies or Lymphomas
A Phase 1, Open-Label, Multicenter Trial Investigating the Safety, Tolerability, and Preliminary Antineoplastic Activity of Sym022 (Anti-LAG-3) in Patients With Advanced Solid Tumor Malignancies or Lymphomas
Descripción general del estudio
Estado
Estado
Condiciones
Condiciones
Intervención / Tratamiento
Intervención / Tratamiento
Descripción detallada
Tipo de estudio
Tipo de estudio
Inscripción (Actual)
Inscripción
Fase
Fase
- Fase 1
Contactos y Ubicaciones
Ubicaciones de estudio
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Ontario
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Toronto, Ontario, Canadá, M5G 2M9
- Princess Margaret Cancer Centre
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Michigan
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Grand Rapids, Michigan, Estados Unidos, 49503
- South Texas Accelerated Research Therapeutics (START) Midwest
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Texas
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Houston, Texas, Estados Unidos, 77030
- The University of Texas MD Anderson Cancer Center
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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:
- Male or female patients, ≥ 18 years of age at the time of obtaining informed consent.
- Documented (histologically- or cytologically-proven) solid tumor malignancy that is locally advanced or metastatic; patients with documented lymphomas.
- Malignancy (solid tumor or lymphoma) that is currently not amenable to surgical intervention due to either medical contraindications or nonresectability of the tumor.
- Refractory to or intolerant of existing therapy(ies) known to provide clinical benefit.
- Measurable or non-measurable disease according to RECIST v1.1 or RECIL 2017.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
- Not of childbearing potential or who agree to use a highly effective method of contraception during the study beginning within 2 weeks prior to the first dose and continuing until 6 months after the last dose of study drug.
Exclusion Criteria:
- Women who are pregnant or lactating, or intending to become pregnant before, during, or within 6 months after the last dose of study drug. Women of childbearing potential (WOCBP) and fertile men with WOCBP partner(s), not using and not willing to use a highly effective method of contraception.
- Known, untreated central nervous system (CNS) or leptomeningeal metastases, or spinal cord compression, patients with any of the above not controlled by prior surgery or radiotherapy, or patients with symptoms suggesting CNS involvement for which treatment is required.
- Hematologic malignancies other than lymphomas.
- Active thrombosis, or a history of deep vein thrombosis (DVT) or pulmonary embolism (PE) within 4 weeks prior to Cycle 1/Day 1 (C1/D1) unless adequately treated and considered stable
- Active uncontrolled bleeding or a known bleeding diathesis
- Clinically significant cardiovascular disease or condition
- Significant pulmonary disease or condition
- Current or recent (within 6 months) significant gastrointestinal (GI) disease or condition.
- An active, known, or suspected autoimmune disease, or a documented history of autoimmune disease or syndrome, requiring systemic steroids or other immunosuppressive medications.
- History of organ transplantation (e.g. stem cell or solid organ transplant)
- History of significant toxicities associated with previous administration of immune checkpoint inhibitors that necessitated permanent discontinuation of that therapy
- Patients with unresolved > Grade 1 toxicity associated with any prior antineoplastic therapy, with exceptions.
- Inadequate recovery from any prior surgical procedure, or having undergone any major surgical procedure within 4 weeks prior to C1/D1.
- Known history of human immunodeficiency virus (HIV) or known active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV).
- Other Inhibitors of LAG-3
- Any antineoplastic agent for the primary malignancy (standard or investigational) without delayed toxicity within 4 weeks or 5 plasma half-lives, whichever is shortest, prior to first administration of study drug and during study
- Any other investigational treatments within 4 weeks prior to and during study
- Radiotherapy for target lesions within 4 weeks prior to first administration of study drug unless PD has been documented in the lesion following treatment, and during study.
- Radiotherapy for non-target lesions within 1 week prior to first administration of study drug
- Immunosuppressive or systemic hormonal therapy
- Prophylactic use of hematopoietic growth factors within 1 week prior to first administration of study drug and during Cycle 1 of study
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- 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: Sym022
Sym022 will be administered at up to 4 planned dose levels.
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Sym022 es un anticuerpo recombinante completamente humano que se une a LAG-3 y bloquea la interacción LAG-3/complejo principal de histocompatibilidad de clase II (MHC-II), lo que permite una mayor proliferación de células T y producción de citoquinas.
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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Assessment of Treatment Related Adverse Events (AEs).
Periodo de tiempo: 19 months
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Assess the safety, tolerability and dose-limiting toxicities of Sym022 on a Q2W schedule to establish the MTD and/or RP2D.
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19 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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Evaluation of the Immunogenicity of Sym022.
Periodo de tiempo: 19 months
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Serum sampling and incidence (%) per dose level to assess the potential for anti-drug antibody (ADA) formation.
Count of participants show the number of participants who were tested positive for anti-Sym022 ADA.
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19 months
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Evaluation of Objective Response (OR) or Stable Disease (SD).
Periodo de tiempo: 13 months
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Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1), Response Evaluation Criteria in Lymphomas 2017 (RECIL 2017), or Immunotherapeutics Response Evaluation Criteria in Solid Tumors (iRECIST), depending on tumor type.
The numbers shown below correspond to the values related to RECIST v1.1.
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13 months
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Time to Progression (TTP) of Disease.
Periodo de tiempo: 13 months
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Based on time of enrollment to first evidence of progression on imaging studies, as assessed by RECIST v1.1, RECIL 2017, or iRECIST, depending on tumor type.
The numbers shown below correspond to the values related to RECIST v1.1.
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13 months
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Area Under the Concentration-time Curve in a Dosing Interval (AUC).
Periodo de tiempo: 19 months
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Will be estimated using non-compartmental methods and actual timepoints.
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19 months
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Maximum Concentration (Cmax)
Periodo de tiempo: 0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
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Will be derived from observed data.
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0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
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Time to Reach Maximum Concentration (Tmax)
Periodo de tiempo: 0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
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Will be derived from observed data.
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0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
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Trough Concentration (Ctrough)
Periodo de tiempo: 0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
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Will be derived from observed data.
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0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
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Terminal Elimination Half-life (T½)
Periodo de tiempo: 0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
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Will be estimated using non-compartmental methods and actual timepoints.
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0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
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Clearance (CL)
Periodo de tiempo: 0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
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Will be estimated using non-compartmental methods and actual timepoints.
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0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
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Colaboradores e Investigadores
Patrocinador
Patrocinador
Investigadores
Investigadores
- Investigador principal: Lillian Siu, MD, FRCPC, Princess Margaret Cancer Centre
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Inicio del estudio
Finalización primaria (Actual)
Finalización primaria
Finalización del estudio (Actual)
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
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
Otros números de identificación del estudio
- Sym022-01
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (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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