Estudo para avaliar a segurança e eficácia de AZD2936 em participantes com câncer de pulmão de células não pequenas avançado ou metastático (ARTEMIDE-01)
Fase I/II, aberto, escalonamento de dose e estudo de expansão de dose para avaliar a segurança, farmacocinética, farmacodinâmica e eficácia do anticorpo anti-TIGIT/anti-PD-1 AZD2936 em participantes com câncer de pulmão de células não pequenas avançado ou metastático
This is a Phase I/II study designed to evaluate if experimental anti-TIGIT/anti-PD-1 bispecific antibody rilvegostomig (AZD2936) is safe, tolerable and efficacious in participants with Advanced or Metastatic Non-small Cell Lung Cancer.
Visão geral do estudo
Status
Status
Condições
Condições
Intervenção / Tratamento
Intervenção / Tratamento
Descrição detalhada
This is a first-time-in-human (FTIH), open-label, multicenter, multi-part, dose-escalation and dose-expansion study to evaluate the safety, pharmacokinetics (PK), pharmacodynamics, and efficacy of rilvegostomig (AZD2936) in adult participants with stage III unresectable or stage IV NSCLC. The study includes 4 parts: Part A (dose escalation) and Parts B-E (dose expansion).
Tipo de estudo
Tipo de estudo
Inscrição (Real)
Inscrição
Estágio
Estágio
- Fase 2
- Fase 1
Contactos e Locais
Locais de estudo
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Melbourne, Austrália, 3000
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Florianópolis, Brasil, 88034-000
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Natal, Brasil, 59075-740
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Porto Alegre, Brasil, 90035903
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Rio de Janeiro, Brasil, 20231-050
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São Paulo, Brasil, 01246-000
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Anderlecht, Bélgica, 1070
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Leuven, Bélgica, 3000
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Chengdu, China, 610041
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Chongqing, China, 400030
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Seoul, Coréia do Sul, 03722
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Seoul, Coréia do Sul, 05505
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Seoul, Coréia do Sul, 03082
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Copenhagen, Dinamarca, 2100
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Barcelona, Espanha, 08035
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Madrid, Espanha, 28041
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Madrid, Espanha, 28027
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Illinois
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Chicago, Illinois, Estados Unidos, 60637
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Minnesota
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Rochester, Minnesota, Estados Unidos, 55905
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Virginia
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Fairfax, Virginia, Estados Unidos, 22031
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Dijon, França, 21079
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Toulouse, França, 31059
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Tbilisi, Geórgia, 0112
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Groningen, Holanda, 9713 GZ
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Leiden, Holanda, 2333 ZA
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Utrecht, Holanda, 3584 CX
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Kashiwa, Japão, 227-8577
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Niigata, Japão, 951-8566
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Sendai, Japão, 981-0914
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Tokyo, Japão, 104-0045
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Kuala Lumpur, Malásia, 59100
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Kuching, Malásia, 93586
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Chisinau, Moldávia, MD-2025
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Bangkok, Tailândia, 10700
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Chanthaburi, Tailândia, 22000
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Muang, Tailândia, 50200
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Taichung, Taiwan, 40705
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Taichung, Taiwan, 40201
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Tainan, Taiwan, 70403
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Taipei, Taiwan, 110
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Critérios de participação
Critérios de elegibilidade
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Inclusion Criteria:
- Written informed consent
- Aged 18 or above
- Part A and Part B: Unresectable stage III or stage IV squamous or non-squamous NSCLC not amenable to curative surgery or radiation. Part C and Part D: Stage IV squamous or non-squamous NSCLC not amenable to curative surgery or radiation. Part E: Stage IV squamous NSCLC not amenable to curative surgery or radiation.
- Documented PD-L1 expression by PD-L1 IHC per local report.
- Part A and Part B: Confirmed progression during treatment with a CPI-including regimen.
- Part C and Part D: No prior I/O treatment for metastatic NSCLC.
- Part E: No prior treatment for metastatic NSCLC.
- ECOG performance status of 0 or 1 at enrolment.
- Life expectancy of ≥ 12 weeks at enrolment.
- Have at least 1 measurable lesion per RECIST v1.1.
- Adequate bone marrow, liver and kidney function
Exclusion Criteria:
- Sensitizing epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) fusion
- Documented test result for any other known genomic alteration for which a targeted therapy is approved in first line per local standard of care (e.g. ROS1, NTRK fusions, BRAF, V600E mutation)
- Previous treatment with an anti-TIGIT therapy
- Any concurrent chemotherapy, radiotherapy, investigational, biologic, or hormonal therapy for cancer treatment.
- Part A and Part B: Primary or secondary resistance after treatment with 2 or more regiments including a CPI.
- Part C and Part D: Any prior systemic treatment with an immune oncology agent (prior administration of immune-oncology agent for curative intent to treat other invasive malignancy is permitted).
Treatment with one previous systemic chemotherapy will be allowed.
- Part E: Any prior systemic treatment for metastatic NSCLC, including but not limited to chemotherapy, anti-PD-1, anti-PD-L1, anti-CTLA-4.
- Symptomatic central nervous system (CNS) metastasis.
- Thromboembolic event within 3 months prior to enrolment.
- Other invasive malignancy within 2 years prior to screening.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Não randomizado
- Modelo Intervencional: Atribuição sequencial
- Mascaramento: Nenhum (rótulo aberto)
Número de braços
Armas e Intervenções
Grupo de Participantes / BraçoGrupo de Participantes / Braço |
Intervenção / TratamentoIntervenção / Tratamento |
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Experimental: Dose Escalation Part A: Checkpoint inhibitor (CPI) experienced Non-small Cell Lung Cancer (NSCLC)
Rilvegostomig Intravenous (IV) monotherapy |
Anti-TIGIT/Anti-PD-1 Bispecific Antibody
Outros nomes:
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Experimental: Dose Expansion Part B: CPI experienced NSCLC
Rilvegostomig IV monotherapy |
Anti-TIGIT/Anti-PD-1 Bispecific Antibody
Outros nomes:
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Experimental: Dose Expansion Part C: CPI Naive NSCLC
Rilvegostomig IV monotherapy |
Anti-TIGIT/Anti-PD-1 Bispecific Antibody
Outros nomes:
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Experimental: Dose Expansion Part D: CPI Naive NSCLC
Rilvegostomig IV monotherapy |
Anti-TIGIT/Anti-PD-1 Bispecific Antibody
Outros nomes:
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Experimental: Dose Expansion Part E: treatment Naive Squamous NSCLC
Rilvegostomig IV monotherapy |
Anti-TIGIT/Anti-PD-1 Bispecific Antibody
Outros nomes:
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O que o estudo está medindo?
Medidas de resultados primários
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
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Percentage of participants with adverse events (AEs) and immune mediated AEs (imAEs), serious AEs (SAEs), dose limiting toxicities (DLTs), vital signs, and abnormal laboratory parameters
Prazo: Part A, B, C, D and E: From the time of informed consent until 90 days after the last dose of rilvegostomig
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A DLT is a toxicity defined by the study protocol that occurs from the first dose of study intervention up to the end of the DLT evaluation period that is assessed as clearly unrelated to the primary disease or intercurrent illness. |
Part A, B, C, D and E: From the time of informed consent until 90 days after the last dose of rilvegostomig
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Rate of rilvegostomig discontinuation due to toxicity
Prazo: Part A, B, C, D and E: From first dose to the last dose of rilvegostomig (an average of 6 months)
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Percentage of participants with AEs leading to discontinuation of rilvegostomig |
Part A, B, C, D and E: From first dose to the last dose of rilvegostomig (an average of 6 months)
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Objective Response Rate (ORR)
Prazo: Part B, C, D and E: From first dose of rilvegostomig to progressive disease (PD) or death in the absence of disease progression (approximately 2 years)
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Percentage of participants with a confirmed Complete Response (CR) or Partial Response (PR) according to RECIST v1.1 |
Part B, C, D and E: From first dose of rilvegostomig to progressive disease (PD) or death in the absence of disease progression (approximately 2 years)
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Medidas de resultados secundários
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
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ORR
Prazo: Part A: From first dose of rilvegostomig to PD or death in the absence of disease progression (approximately 2 years).
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Percentage of participants with a confirmed CR or PR according to RECIST v1.1 |
Part A: From first dose of rilvegostomig to PD or death in the absence of disease progression (approximately 2 years).
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Disease control rate (DCR)
Prazo: Part A, B, C, E: From first dose of rilvegostomig to PD or death in the absence of disease progression (approximately 2 years). Part D: From randomization to PD or death in the absence of disease progression (approximately 2 years).
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Percentage of participants who have a best objective response of confirmed CR or PR or who have SD lasting for at least a certain time of period after start of treatment |
Part A, B, C, E: From first dose of rilvegostomig to PD or death in the absence of disease progression (approximately 2 years). Part D: From randomization to PD or death in the absence of disease progression (approximately 2 years).
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Duration of response (DoR)
Prazo: Part A, B, C, D and E: From first dose of rilvegostomig to PD or death in the absence of disease progression (approximately 2 years).
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The time from first response according to RECIST v1.1 until progression or death in the absence of disease progression |
Part A, B, C, D and E: From first dose of rilvegostomig to PD or death in the absence of disease progression (approximately 2 years).
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Durable response rate (DRR)
Prazo: Part A, B, C, D and E: From first dose of rilvegostomig to PD or death in the absence of disease progression (approximately 2 years).
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The percentage of participants according to RECIST v1.1 with a confirmed CR or PR lasting 6 months or more |
Part A, B, C, D and E: From first dose of rilvegostomig to PD or death in the absence of disease progression (approximately 2 years).
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Progression-free survival (PFS)
Prazo: Part B, C, E: From first dose of rilvegostomig to PD or death in the absence of disease progression (approximately 2 years). Part D: From randomization to PD or death in the absence of disease progression (approximately 2 years).
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The time from first dose of study intervention until the date of objective disease progression or death in the absence of disease progression |
Part B, C, E: From first dose of rilvegostomig to PD or death in the absence of disease progression (approximately 2 years). Part D: From randomization to PD or death in the absence of disease progression (approximately 2 years).
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Measure the receptor occupancy (RO) of TIGIT and PD-1 on peripheral blood
Prazo: Part A, B: From first dose of study intervention, at predefined intervals throughout the administration of rilvegostomig (approximately 2 years). The predefined intervals for Part A will be different from Part B.
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Evaluation of the target engagement of rilvegostomig in peripheral blood |
Part A, B: From first dose of study intervention, at predefined intervals throughout the administration of rilvegostomig (approximately 2 years). The predefined intervals for Part A will be different from Part B.
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PK of rilvegostomig: Maximum plasma concentration of the study drug (Cmax)
Prazo: From first dose of study intervention, at predefined intervals throughout the administration of rilvegostomig (approximately 2 years). The predefined intervals for Part A will be different from Part B, C, D and E.
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Maximum observed plasma concentration of rilvegostomig |
From first dose of study intervention, at predefined intervals throughout the administration of rilvegostomig (approximately 2 years). The predefined intervals for Part A will be different from Part B, C, D and E.
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PK of rilvegostomig: Area under the concentration-time curve (AUC)
Prazo: From first dose of study intervention, at predefined intervals throughout the administration of rilvegostomig (approximately 2 years). The predefined intervals for Part A will be different from Part B, C, D and E.
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Area under the plasma concentration-time curve |
From first dose of study intervention, at predefined intervals throughout the administration of rilvegostomig (approximately 2 years). The predefined intervals for Part A will be different from Part B, C, D and E.
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PK of rilvegostomig: Clearance
Prazo: From first dose of study intervention, at predefined intervals throughout the administration of rilvegostomig (approximately 2 years). The predefined intervals for Part A will be different from Part B, C, D and E.
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A pharmacokinetic measurement of the volume of plasma from which the study intervention is completely removed per unit time. |
From first dose of study intervention, at predefined intervals throughout the administration of rilvegostomig (approximately 2 years). The predefined intervals for Part A will be different from Part B, C, D and E.
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PK of rilvegostomig: Terminal elimination half-life (t 1/2)
Prazo: From first dose of study intervention, at predefined intervals throughout the administration of rilvegostomig (approximately 2 years). The predefined intervals for Part A will be different from Part B, C, D and E.
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Terminal elimination half life |
From first dose of study intervention, at predefined intervals throughout the administration of rilvegostomig (approximately 2 years). The predefined intervals for Part A will be different from Part B, C, D and E.
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Incidence of anti-drug antibodies (ADA) against rilvegostomig in serum
Prazo: From first dose of study intervention, at predefined intervals throughout the administration of rilvegostomig (approximately 2 years). The predefined intervals for Part A will be different from Part B, C, D and E.
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Immunogenicity of rilvegostomig |
From first dose of study intervention, at predefined intervals throughout the administration of rilvegostomig (approximately 2 years). The predefined intervals for Part A will be different from Part B, C, D and E.
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Colaboradores e Investigadores
Patrocinador
Patrocinador
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Início do estudo
Conclusão Primária (Estimado)
Conclusão Primária
Conclusão do estudo (Estimado)
Conclusão do estudo
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Primeira postagem
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última Atualização Postada
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Processos Patológicos
- Neoplasias por local
- Neoplasias
- Doenças Respiratórias
- Doenças pulmonares
- Neoplasias do Trato Respiratório
- Neoplasias Torácicas
- Processos Neoplásicos
- Neoplasias Pulmonares
- Carcinoma Broncogênico
- Neoplasias Brônquicas
- Condições Patológicas, Sinais e Sintomas
- Neoplasia Metástase
- Carcinoma pulmonar de células não pequenas
- Doença de Parkinson 4, Corpo Autossômico Dominante de Lewy
Outros números de identificação do estudo
Outros números de identificação do estudo
- D7020C00001
- 2021-000857-23 (Número EudraCT)
- 2023-508262-15-00 (Identificador de registro: EU CT Number)
- 2023 (Concessão/Contrato do NIH dos EUA)
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
Descrição do plano IPD
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.
All request 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.
Prazo de Compartilhamento de IPD
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Critérios de acesso de compartilhamento IPD
When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level datain an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access.For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Tipo de informação de suporte de compartilhamento de IPD
- PROTOCOLO DE ESTUDO
- SEIVA
Informações sobre medicamentos e dispositivos, documentos de estudo
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