A First-in-Human Study Investigating BG-85738 Alone or in Combination With Other Antitumor Agents in Patients With Advanced or Metastatic Solid Tumors With Rat Sarcoma Virus (RAS) Mutations
A Phase 1a/1b Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of BG-85738, Alone or in Combination With Other Antitumor Agents, in Patients With Advanced or Metastatic Solid Tumors With RAS Mutations
Visão geral do estudo
Status
Intervenção / Tratamento
Descrição detalhada
A solid tumor is an abnormal mass of tissue caused by the uncontrolled growth of cells which can develop in organs, bones, or soft tissues. An advanced or metastatic solid tumor is a cancer that has either grown into nearby tissues ("advanced") or spread to distant parts of the body ("metastatic").
Many types of solid cancers have a change (mutation) in a gene called RAS gene. In normal cells, RAS proteins work by controlling when cells grow and divide. RAS mutations in cancer cells might lead to hyperactivation of the RAS proteins, which can result in continuous and uncontrolled growth of cancer cells. BG-85738 is a new experimental medicine that has been designed to block RAS proteins that are hyperactive.
The purpose of this study is to test whether BG-85738 is safe and if it can help to treat adults with advanced or metastatic solid tumors with a RAS mutation. This study has two parts, one called dose escalation, and one called safety expansion. During the dose escalation part, the study doctors will test different doses of the study drug[s] to find the recommended dose that people can take without having serious side effects.
During the dose expansion part, the study doctors will test the study drug in a larger number of people using the dose[s] identified from dose escalation.
The study will enroll patients at multiple centers worldwide who have been diagnosed with an advanced solid tumor that has a RAS gene mutation. The overall time to participate in this study is approximately 13 to 24 months. Participants will make regular visits to the clinic for treatment, health checks, blood tests, and for tumor and imaging tests.
Tipo de estudo
Inscrição (Estimado)
Estágio
- Fase 1
Contactos e Locais
Contato de estudo
- Nome: Study Director
- Número de telefone: 877-828-5568
- E-mail: clinicaltrials@beonemed.com
Locais de estudo
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Queensland
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South Brisbane, Queensland, Austrália, QLD 4101
- Recrutamento
- ICON Cancer Centre South Brisbane
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Victoria
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Malvern, Victoria, Austrália, VIC 3144
- Recrutamento
- Cabrini Hospital Malvern
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
- Adulto
- Adulto mais velho
Aceita Voluntários Saudáveis
Descrição
Inclusion Criteria:
Participants are eligible to be included in the study only if they meet all the following criteria:
- Participants must sign the informed consent form and be capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
- Participants must be ≥ 18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place, whichever is older), at the time of signing the ICF.
- Participants with histologically or cytologically confirmed advanced, metastatic, and unresectable solid tumors and meet study part and cohort-specific criteria
- Participants must have evidence of a RAS mutation defined as a nonsynonymous mutation in Kirsten rat sarcoma viral oncogene homolog (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS), or Harvey rat sarcoma viral oncogene homolog (HRAS) at codons 12, 13, or 61 (G12, G13, or Q61), based on testing of either tumor tissue or liquid biopsy (blood or plasma) as determined by the local laboratory
Exclusion Criteria:
Participants are excluded from the study if they meet any of the following criteria:
- Participants who have prior RAS-targeted therapy, including, but not limited to, KRAS mutation-specific inhibitors (with the exception of participants with NSCLC and colorectal cancer who received a G12C inhibitor), pan-KRAS inhibitors, and pan-RAS inhibitors.
- Participants who have a history of severe allergic reactions or hypersensitivity to the active ingredient and excipients of study treatment.
- Participants who are unable to comply with the requirements of the protocol.
- Participants with active leptomeningeal disease or uncontrolled, untreated brain metastases
- Participants with any malignancy ≤ 3 years before the first dose of study treatment except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated curatively (e.g., resected basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast).
- Participants with active hepatitis C.
- Participants with medical history of untreated Human Immunodeficiency Virus infection.
Note: Other protocol defined criteria may apply.
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: Phase 1a: Part A- Monotherapy Dose escalation and safety
Ascending dose levels of BG-85738 will be evaluated as monotherapy in participants with advanced or metastatic solid tumors with RAS mutations.
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Administered orally
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Experimental: Phase 1a: Part B - Combination therapy Dose escalation
Sequential dose levels of BG-85738, selected based on Part A data, will be evaluated in combination with tislelizumab or in combination with cetuximab.
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Administrado por via intravenosa
Administrado por via intravenosa
Administered orally
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Experimental: Phase 1b: Part C- Monotherapy dose expansion
Participants with selected tumor types will receive BG-85738 monotherapy at the RDFE(s) identified in Phase 1a Part A.
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Administered orally
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Experimental: Phase 1b: Part D - Combination therapy dose expansion
Participants with select tumor types will receive BG-85738 in combination with tislelizumab or in combination with cetuximab at the RDFE(s) identified in Phase 1a Part B
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Administrado por via intravenosa
Administrado por via intravenosa
Administered orally
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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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Phase 1a (Part A and Part B): Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Prazo: From first dose to 30 days after last dose or initiation of a new anticancer therapy, whichever occurs first, up to approximately 24 months
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An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporarily associated with the use of study treatment, whether considered related to study treatment or not. An SAE is any untoward medical occurrence that, at any dose,
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From first dose to 30 days after last dose or initiation of a new anticancer therapy, whichever occurs first, up to approximately 24 months
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Phase 1a (Parts A and B): Number of Participants with Dose Limiting Toxicity (DLT)
Prazo: Up to approximately 1 month
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Up to approximately 1 month
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Phase 1a (Parts A and B): Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BG-85738 as monotherapy or in combination with other antitumor agents
Prazo: Up to approximately 1 month
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MTD is defined as the highest dose level with the target DLT closest but not exceeding 0.33. MAD is defined as the maximum administered dose and it is used when MTD is not reached. |
Up to approximately 1 month
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Phase 1a: Recommended Dose for Expansion (RDFE) of BG-85738
Prazo: Up to approximately 1 month
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Up to approximately 1 month
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Part 1b (Parts C and D): Overall Response Rate (ORR)
Prazo: Up to approximately 24 months
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ORR is defined as the percentage of participants who achieve complete response (CR) or partial response (PR).
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Up to approximately 24 months
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Phase 1b Dose Expansion: Recommended Phase 2 dose (RP2D) of BG-85738
Prazo: Up to approximately 24 months
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Up to approximately 24 months
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Phase 1a (Part A and Part B): Terminal Half Life (t1/2) of BG-85738
Prazo: Up to approximately 2 months
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Up to approximately 2 months
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Phase 1a (Part A and Part B): Area Under the Plasma Concentration-Time Curve (AUC) of BG-85738
Prazo: Up to approximately 2 months
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Up to approximately 2 months
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Phase 1a (Part A and Part B): Minimum Observed Serum Concentration (Ctrough) of BG-85738
Prazo: Up to approximately 2 months
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Up to approximately 2 months
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Phase 1a (Part A and Part B): Maximum Observed Plasma Concentration (Cmax) of BG-85738
Prazo: Up to approximately 2 months
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Up to approximately 2 months
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Phase 1a (Part A and Part B): Overall Response Rate (ORR)
Prazo: Up to approximately 24 months
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ORR is defined as the percentage of participants who achieve complete response (CR) or partial response (PR).
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Up to approximately 24 months
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Phase 1b (Parts C and D): Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Prazo: From first dose to 30 days after last dose or initiation of a new anticancer therapy, whichever occurs first, up to approximately 24 months
|
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporarily associated with the use of study treatment, whether considered related to study treatment or not. An SAE is any untoward medical occurrence that, at any dose,
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From first dose to 30 days after last dose or initiation of a new anticancer therapy, whichever occurs first, up to approximately 24 months
|
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Phase 1b (Part C and D): Duration of response (DOR)
Prazo: Up to approximately 24 months
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DOR is defined as the time from the first determination of an overall response until the first documentation of progression or death, whichever comes first.
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Up to approximately 24 months
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Phase 1b (Part C and D): Disease control rate (DCR)
Prazo: Up to approximately 24 months
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DCR is defined as the percentage of participants with best of response of a CR, PR, and stable disease.
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Up to approximately 24 months
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Phase 1b (Part C and D): Time to response (TTR)
Prazo: Up to approximately 24 months
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TTR is defined as the time from date of the first dose of study treatment to the first overall response.
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Up to approximately 24 months
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Phase 1b (Part C and D): Progression-free survival (PFS) as assessed by the investigator
Prazo: Up to approximately 24 months
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PFS is defined as the time from the date of the first dose of study treatment to the date of the first documentation of progressive disease or death, whichever occurs first, as assessed by the investigator per RECIST v1.1
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Up to approximately 24 months
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Phase 1b (Part C): Intracranial Objective Response Rate (iORR)
Prazo: Up to approximately 24 months
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Intracranial objective response rate is defined as the percentage of patients with a best overall Intracranial response of CR or PR according to modified (m)RECIST v1.1 per Investigator assessment.
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Up to approximately 24 months
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Phase 1b (Part C): Intracranial Duration of Response (iDOR)
Prazo: Up to approximately 24 months
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iDOR is defined as the time from the first determination of an overall intracranial response until the first documentation of progression or death, whichever comes first, with intracranial assessments by the investigator via modified RECIST v1.1 adapted for brain metastases.
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Up to approximately 24 months
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Phase 1b (Part C): Intracranial Progression-free survival (iPFS) as determined from tumor assessments by the investigator
Prazo: Up to approximately 24 months
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iPFS is defined as the time from the date of the first dose of study treatment to the date of the first documentation of progressive disease or death, whichever occurs first.
PFS is determined from tumor assessments by the investigator per a modified RECIST v1.1 adapted for brain metastases
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Up to approximately 24 months
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Diretor de estudo: Study Director, BeOne Medicine
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
- Processos Patológicos
- Neoplasias
- Processos Neoplásicos
- Condições Patológicas, Sinais e Sintomas
- Neoplasia Metástase
- Aminoácidos, peptídeos e proteínas
- Proteínas
- Anticorpos, monoclonais, humanizados
- Anticorpos, monoclonais
- Anticorpos
- Imunoglobulinas
- Imunoproteínas
- Proteínas sanguíneas
- Globulinas de soro
- Globulins
- Cetuximabe
- tislelizumab
Outros números de identificação do estudo
- BG-85738-101
- 2026-526560-20-00 (Ctis)
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
Descrição do plano IPD
BeOne shares data on completed studies responsibly and provides qualified scientific and medical researchers access to data and supporting documentation for clinical trials in dossiers for medicines and indications after submission and approval in the United States, China, and Europe. Clinical trials supporting subsequent local approvals, new indications, or combination products are eligible for sharing once corresponding regulatory approvals are achieved.
BeOne shares data only when permitted by applicable data privacy and security laws and regulations, when it is feasible to do so without compromising the privacy of study participants, and other considerations.
Qualified researchers with appropriate competencies who are engaged in novel scientific research may submit a request for participant-level data with a research proposal for BeOne review. Research teams must include a biostatistician and sign a Data Sharing Agreement prior to receiving access to clinical trial data.
Prazo de Compartilhamento de IPD
Critérios de acesso de compartilhamento IPD
Tipo de informação de suporte de compartilhamento de IPD
- PROTOCOLO DE ESTUDO
- SEIVA
- CSR
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