Phase 1 Study of 6MW5311 in Adults With Relapsed or Refractory Blood Cancers
A Phase 1, Safety, Pharmacokinetic, Immunogenicity, and Preliminary Efficacy Study of 6MW5311 in Relapsed/Refractory Acute Myeloid Leukemia (AML) Patients, in Chronic Myelomonocytic Leukemia (CMML) Patients and Multiple Myeloma (MM) Patients
To assess safety and tolerability at increasing dose levels of 6MW5311 in successive cohorts of participants with MM, AML and CMML in order to estimate the maximum tolerated dose (MTD) and select the recommended Phase 2 dose (RP2D) or the recommended expansion dose (RED).
Visão geral do estudo
Descrição detalhada
This is a 2-part, open-label, multicenter, First-in-Human Phase 1 clinical trial consisting of dose escalation (Part 1) and dose expansion (Part 2). Part 1 will evaluate the safety and tolerability, immunogenicity, PK/PD, biomarker, and preliminary clinical activities of 6MW5311. Part 2 will select appropriate dose(s) for expansion based on preliminary efficacy, safety, immunogenicity, PK/PD, and biomarkers data from Part 1, and will further assess the safety, PK, biomarker, and efficacy of 6MW5311. Upon completion of the Phase 1 clinical trial and findings from non-clinical studies, the recommended expansion dose (RED) or recommended Phase 2 dose (RP2D) of 6MW5311 in patients with hematological malignancies will be determined.
Tipo de estudo
Inscrição (Estimado)
Estágio
- Fase 1
Contactos e Locais
Contato de estudo
- Nome: Jiangjiang Lv
- Número de telefone: +86-021-58585793
- E-mail: jiangjiang.lv@mabwell.com
Locais de estudo
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Shanghai Municipality
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Shanghai, Shanghai Municipality, China, 200025
- Recrutamento
- Shanghai Jiao Tong University School of Medicine, Ruijin Hospital
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Contato:
- Jianqing Mi, PhD
- Número de telefone: +86-13524488296
- E-mail: jianqingmi@shsmu.edu.cn
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Inclusion Criteria:
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Age 18 years or older at the time of signing the informed consent form; male or female.
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Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 for the dose-escalation part, or 0 to 2 for the dose-expansion part.
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Life expectancy greater than 3 months.
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Multiple myeloma (MM): histologically and/or cytologically confirmed MM per International Myeloma Working Group (IMWG) 2016 criteria, with at least 3 prior lines of MM therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.
- Chronic myelomonocytic leukemia (CMML): morphologically confirmed by bone marrow examination per World Health Organization (WHO) 2016 classification, with relapsed disease or failure of prior therapy.
- Acute myeloid leukemia (AML; dose-expansion part only): morphologically confirmed acute myelomonocytic leukemia or acute monocytic leukemia per WHO 2016 classification, meeting the protocol definition of relapsed or refractory AML.
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MM only: measurable disease at screening.
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Adequate hematologic function at screening:
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Able to understand and comply with the protocol requirements, willing to participate in the clinical study, and able to provide written informed consent.
Exclusion Criteria:
- 1. AML and CMML only: any other anticancer therapy within 2 weeks before the first dose of study drug.
MM only: prior anticancer therapy within the following intervals before the first dose of study drug:
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small-molecule targeted therapy within 4 weeks or 5 half-lives, whichever is shorter;
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antibody therapy within 3 weeks;
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cytotoxic chemotherapy, proteasome inhibitor therapy, or traditional Chinese medicine (including Chinese patent medicine) with an anticancer indication within 2 weeks;
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immunomodulatory agent within 1 week;
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chimeric antigen receptor T-cell (CAR-T) therapy within 3 months;
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radiotherapy within 1 week. 2. Receipt of any other investigational drug within 4 weeks before the first dose of study drug.
3. Prior allogeneic stem cell transplant; or autologous stem cell transplant within 3 months before the first dose of study drug.
4. Planned stem cell transplant during the study. 5. Prior treatment with a LILRB4-targeted therapy.
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)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
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Experimental: Part 1 - Dose Escalation (6MW5311)
A modified 3+3 design with accelerated titration will be used to evaluate planned dose levels. |
A bispecific T cell engager (TCE) antibody: bivalent binding to LILRB4 on tumor cells and monovalent binding to CD3 on T cells. |
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Experimental: Part 2 - Dose Expansion (6MW5311)
Participants with chronic myelomonocytic leukemia (CMML), multiple myeloma (MM), or relapsed or refractory acute myeloid leukemia (AML; acute myelomonocytic or monocytic subtypes) will receive 6MW5311 at the dose level(s) selected by the Safety Review Committee from Part 1. |
A bispecific T cell engager (TCE) antibody: bivalent binding to LILRB4 on tumor cells and monovalent binding to CD3 on T cells. |
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Number of participants with dose-limiting toxicities (DLTs)
Prazo: From the first dose of Cycle 1 through Day 28 of Cycle 1 (each cycle is 28 days)
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DLTs are adverse events considered related to 6MW5311 (definitely, probably, or possibly related) that occur during the dose-limiting toxicity observation period (first 28 days after the first dose of Cycle 1). DLTs are defined per the protocol and graded per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 6.0. |
From the first dose of Cycle 1 through Day 28 of Cycle 1 (each cycle is 28 days)
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Number of participants with treatment-emergent adverse events (TEAEs)
Prazo: From first dose through 28 days after the last dose, an average of 1 year
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TEAEs will be graded per NCI CTCAE version 6.0 and coded by system organ class and preferred term. |
From first dose through 28 days after the last dose, an average of 1 year
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Overall response rate (ORR)
Prazo: From first dose through end of treatment, an average of 1 year
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ORR is the proportion of participants with a confirmed response. For multiple myeloma: the sum of confirmed stringent complete response, complete response, very good partial response, and partial response per International Myeloma Working Group (IMWG) 2016 criteria. For acute myeloid leukemia: the sum of confirmed complete response, complete remission with incomplete hematologic recovery, complete remission with partial hematologic recovery, morphologic leukemia-free state, and partial response per European LeukemiaNet (ELN) 2022 criteria. For chronic myelomonocytic leukemia: the sum of confirmed complete response, marrow response, partial response, and clinical benefit per the international MDS/MPN working group criteria. |
From first dose through end of treatment, an average of 1 year
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Maximum observed serum concentration (Cmax) of 6MW5311
Prazo: Through study completion, an average of 1 year
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Cmax is the maximum observed serum concentration of 6MW5311, read directly from the individual serum concentration-time profile after intravenous infusion. |
Through study completion, an average of 1 year
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Area under the serum concentration-time curve (AUC) of 6MW5311
Prazo: Through study completion, an average of 1 year
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Through study completion, an average of 1 year
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Time to maximum observed serum concentration (Tmax) of 6MW5311
Prazo: Through study completion, an average of 1 year
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Through study completion, an average of 1 year
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Terminal elimination half-life (t1/2) of 6MW5311
Prazo: Through study completion, an average of 1 year
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Through study completion, an average of 1 year
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Systemic clearance (CL) of 6MW5311
Prazo: Through study completion, an average of 1 year
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Through study completion, an average of 1 year
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Volume of distribution (V) of 6MW5311
Prazo: Through study completion, an average of 1 year
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Through study completion, an average of 1 year
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Colaboradores e Investigadores
Patrocinador
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
- Doenças Vasculares
- Doenças cardiovasculares
- Neoplasias
- Doenças do sistema imunológico
- Neoplasias por Tipo Histológico
- Doenças Hematológicas
- Distúrbios Linfoproliferativos
- Distúrbios imunoproliferativos
- Neoplasias de Células Plasmáticas
- Distúrbios hemostáticos
- Paraproteinemias
- Distúrbios das Proteínas Sanguíneas
- Distúrbios hemorrágicos
- Doenças hemic e linfáticas
- Mieloma múltiplo
Outros números de identificação do estudo
- 6MW5311-CP101
Plano para dados de participantes individuais (IPD)
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