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Sym022 (Anti-LAG-3) in Patients With Advanced Solid Tumor Malignancies or Lymphomas

1 de febrero de 2021 actualizado por: Symphogen A/S

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

This is the first study to test Sym022 in humans. The primary purpose of this study is to see if Sym022 is safe and tolerable for patients with locally advanced/unresectable or metastatic solid tumor malignancies or lymphomas that are refractory to available therapy or for which no standard therapy is available.

Descripción general del estudio

Estado

Terminado

Intervención / Tratamiento

Descripción detallada

This study will evaluate the preliminary safety, tolerability, and dose-limiting toxicities (DLTs) of Sym022, an anti-lymphocyte activation gene 3 (anti-LAG-3) monoclonal antibody (mAb). The goal is to establish the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of sequential escalating doses of Sym022 when administered once every 2 weeks (Q2W) by intravenous (IV) infusion to patient cohorts with locally advanced/ unresectable or metastatic solid tumor malignancies or lymphomas that are refractory to available therapy or for which no standard therapy is available. If an MTD is not identified, a maximum administered dose (MAD) will be determined. Sym022 will be given to patients in escalating dose cohorts; each patient will be given one fixed dose level.

Tipo de estudio

Intervencionista

Inscripción (Actual)

15

Fase

  • Fase 1

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Ubicaciones de estudio

    • Ontario
      • Toronto, Ontario, Canadá, M5G 2M9
        • Princess Margaret Cancer Centre
    • Michigan
      • Grand Rapids, Michigan, Estados Unidos, 49503
        • South Texas Accelerated Research Therapeutics (START) Midwest
    • Texas
      • Houston, Texas, Estados Unidos, 77030
        • The University of Texas MD Anderson Cancer Center

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

18 años y mayores (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

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

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿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)

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Experimental: Sym022
Sym022 will be administered at up to 4 planned dose levels.
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:
  • Anti-LAG-3

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Assessment of Treatment Related Adverse Events (AEs).
Periodo de tiempo: 19 months
Assess the safety, tolerability and dose-limiting toxicities of Sym022 on a Q2W schedule to establish the MTD and/or RP2D.
19 months

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Evaluation of the Immunogenicity of Sym022.
Periodo de tiempo: 19 months
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.
19 months
Evaluation of Objective Response (OR) or Stable Disease (SD).
Periodo de tiempo: 13 months
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.
13 months
Time to Progression (TTP) of Disease.
Periodo de tiempo: 13 months
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.
13 months
Area Under the Concentration-time Curve in a Dosing Interval (AUC).
Periodo de tiempo: 19 months
Will be estimated using non-compartmental methods and actual timepoints.
19 months
Maximum Concentration (Cmax)
Periodo de tiempo: 0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
Will be derived from observed data.
0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
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)
Will be derived from observed data.
0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
Trough Concentration (Ctrough)
Periodo de tiempo: 0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
Will be derived from observed data.
0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
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)
Will be estimated using non-compartmental methods and actual timepoints.
0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
Clearance (CL)
Periodo de tiempo: 0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
Will be estimated using non-compartmental methods and actual timepoints.
0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

Investigadores

  • Investigador principal: Lillian Siu, MD, FRCPC, Princess Margaret Cancer Centre

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio (Actual)

8 de mayo de 2018

Finalización primaria (Actual)

6 de enero de 2020

Finalización del estudio (Actual)

6 de enero de 2020

Fechas de registro del estudio

Enviado por primera vez

26 de marzo de 2018

Primero enviado que cumplió con los criterios de control de calidad

3 de abril de 2018

Publicado por primera vez (Actual)

5 de abril de 2018

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

18 de febrero de 2021

Última actualización enviada que cumplió con los criterios de control de calidad

1 de febrero de 2021

Última verificación

1 de febrero de 2021

Más información

Términos relacionados con este estudio

Plan de datos de participantes individuales (IPD)

¿Planea compartir datos de participantes individuales (IPD)?

NO

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.

No

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. .

Ensayos clínicos sobre Sym022

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