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- Ensaio Clínico NCT03489369
Sym022 (Anti-LAG-3) in Patients With Advanced Solid Tumor Malignancies or Lymphomas
1 de fevereiro de 2021 atualizado 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.
Visão geral do estudo
Status
Concluído
Condições
Intervenção / Tratamento
Descrição detalhada
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 estudo
Intervencional
Inscrição (Real)
15
Estágio
- Fase 1
Contactos e Locais
Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.
Locais de estudo
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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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Critérios de participação
Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.
Critérios de elegibilidade
Idades elegíveis para estudo
18 anos e mais velhos (Adulto, Adulto mais velho)
Aceita Voluntários Saudáveis
Não
Gêneros Elegíveis para o Estudo
Tudo
Descrição
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
Plano de estudo
Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: N / D
- Modelo Intervencional: Atribuição de grupo único
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
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Experimental: Sym022
Sym022 will be administered at up to 4 planned dose levels.
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Sym022 é um anticorpo totalmente humano recombinante que se liga a LAG-3 e bloqueia a interação LAG-3/complexo principal de histocompatibilidade classe II (MHC-II), permitindo assim o aumento da proliferação de células T e produção de citocinas.
Outros nomes:
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Assessment of Treatment Related Adverse Events (AEs).
Prazo: 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 resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Evaluation of the Immunogenicity of Sym022.
Prazo: 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).
Prazo: 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.
Prazo: 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).
Prazo: 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)
Prazo: 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)
Prazo: 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)
Prazo: 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)
Prazo: 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)
Prazo: 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
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Patrocinador
Investigadores
- Investigador principal: Lillian Siu, MD, FRCPC, Princess Margaret Cancer Centre
Datas de registro do estudo
Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.
Datas Principais do Estudo
Início do estudo (Real)
8 de maio de 2018
Conclusão Primária (Real)
6 de janeiro de 2020
Conclusão do estudo (Real)
6 de janeiro de 2020
Datas de inscrição no estudo
Enviado pela primeira vez
26 de março de 2018
Enviado pela primeira vez que atendeu aos critérios de CQ
3 de abril de 2018
Primeira postagem (Real)
5 de abril de 2018
Atualizações de registro de estudo
Última Atualização Postada (Real)
18 de fevereiro de 2021
Última atualização enviada que atendeu aos critérios de controle de qualidade
1 de fevereiro de 2021
Última verificação
1 de fevereiro de 2021
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- Sym022-01
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
NÃO
Informações sobre medicamentos e dispositivos, documentos de estudo
Estuda um medicamento regulamentado pela FDA dos EUA
Sim
Estuda um produto de dispositivo regulamentado pela FDA dos EUA
Não
Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .
Ensaios clínicos em Sym022
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Symphogen A/SConcluídoLinfoma | Tumor Sólido | Câncer metastáticoCanadá, Estados Unidos
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Symphogen A/SConcluídoTumor Sólido | Câncer metastáticoEstados Unidos, Canadá, França, Espanha