Um Estudo para Saber Mais Sobre a Segurança do BAY 3771249 e a sua Eficácia em Pessoas com Cancro Colorretal Avançado ou Metastático que Tem uma Mutação KRAS G12D
Protocolo Principal: Um estudo aberto para avaliar a segurança, tolerabilidade, farmacocinética, farmacodinâmica e eficácia do BAY 3771249 em monoterapia ou em combinação com outros tratamentos oncológicos em participantes com tumores sólidos que apresentem a mutação KRAS G12D Subprotocolo: Um estudo aberto, multi-coorte para avaliar a segurança, tolerabilidade, farmacocinética, farmacodinâmica e atividade anti-tumoral preliminar do BAY 3771249 em monoterapia e em combinação com Cetuximab em participantes com adenocarcinoma colorretal avançado/metastático que apresente a mutação KRAS G12D
Researchers are looking for a better way to treat people who have advanced or metastatic colorectal cancer (CRC) with a specific mutation, the G12D mutation, in a protein called KRAS.
Colorectal cancer (CRC) is a common type of cancer that affects the large bowel (colon) or the rectum (the section at the end of the bowel). When CRC spreads to other parts of the body, it is called advanced or metastatic CRC. Some people with CRC have the G12D mutation in the KRAS protein. This mutation is linked to a poorer outlook and fewer treatment options. Currently, there are no approved treatments that specifically target this mutation.
KRAS is a protein that helps control how cells grow and divide. When it is mutated, it can cause cells to grow uncontrollably, leading to cancer. The study drug, BAY 3771249, is designed to block the activity of KRAS with G12D mutation, which may help slow or stop the growth of cancer cells. BAY 3771249 can be given alone or together with another drug called cetuximab.
The main purpose of this study is to learn how safe BAY 3771249 is, how well people tolerate it, how the body processes the drug, and whether it can help shrink or control tumors in people with advanced or metastatic CRC that has the KRAS G12D mutation. The study will also look at how BAY 3771249 works when given alone or with cetuximab, especially in people who have already tried other treatments for their cancer.
Researchers will measure, among others:
The number and seriousness of health problems (adverse events) after receiving BAY 3771249.
The number of participants who experience a dose-limiting side effect (DLT) at each dose level.
The number of participants whose tumors shrink or disappear (overall response rate, ORR) as measured by standard criteria.
How much of the drug is in the blood over time (AUC) and the highest amount in the blood (Cmax).
Some participants will receive BAY 3771249 alone (monotherapy), and others will receive BAY 3771249 with cetuximab (combination therapy).
The study will start with lower doses and gradually increase to find the highest safe dose (dosage escalation). After the safe dose is found, more participants may join the study to receive it (dosage expansion). In some parts of the study, participants may be randomly assigned to different groups or doses. The study is open-label, meaning both participants and doctors know which treatment is being given.
An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events, even if they do not think it is related to the study treatment.
The study doctors and their team will contact participants to learn about their health until they complete the study.
If a participant benefits from the treatment, it might be possible to continue receiving BAY 3771249 after the end of the study. The findings from this study may help develop a new treatment option for people with advanced or metastatic CRC with a KRAS G12D mutation.
Visão geral do estudo
Status
Intervenção / Tratamento
Tipo de estudo
Inscrição (Estimado)
Estágio
- Fase 1
Contactos e Locais
Contato de estudo
- Nome: Bayer Clinical Trials Contact
- Número de telefone: 18888422937
- E-mail: clinical-trials-contact@bayer.com
Locais de estudo
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New South Wales
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Albury, New South Wales, Austrália, 2640
- Ainda não está recrutando
- Border Medical oncology - Albury Wodonga Regional Cancer Centre
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Waratah, New South Wales, Austrália, 2298
- Recrutamento
- Calvary Mater Hospital Newcastle - Oncology
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Victoria
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Malvern, Victoria, Austrália, 3144
- Ainda não está recrutando
- Cabrini Health Oncology Research
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East Flanders
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Ghent, East Flanders, Bélgica, 9000
- Ainda não está recrutando
- Ghent University Hospital | Drug Research Unit Department
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Singapore, Cingapura, 119074
- Recrutamento
- National University Hospital Medical Centre
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Singapore, Cingapura, 168583
- Recrutamento
- National Cancer Center Singapore - Oncology Department
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Capital Region / Region Hovedstaden
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Copenhagen, Capital Region / Region Hovedstaden, Dinamarca, 2100
- Ainda não está recrutando
- Rigshospitalet Copenhagen University Hospital | Oncology Department
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Region of Southern Denmark / Region Syddanmark
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Odense, Region of Southern Denmark / Region Syddanmark, Dinamarca, 5000
- Ainda não está recrutando
- Odense University Hospital | Svendborg Sygehus - Oncology Department
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Barcelona
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Barcelona, Barcelona, Espanha, 08035
- Ainda não está recrutando
- Hospital Universitari Vall D Hebron | Oncologia
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Madrid
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Madrid, Madrid, Espanha, 28050
- Ainda não está recrutando
- Hospital Universitario Hm Sanchinarro | Oncologia
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Arizona
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Phoenix, Arizona, Estados Unidos, 85054
- Ainda não está recrutando
- Mayo Clinic - Cancer Center - Phoenix
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California
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Duarte, California, Estados Unidos, 91010
- Recrutamento
- City of Hope - Duarte Cancer Center
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San Diego, California, Estados Unidos, 92037
- Ainda não está recrutando
- UC San Diego Health - Moores Cancer Center
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Colorado
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Denver, Colorado, Estados Unidos, 80218
- Retirado
- Sarah Cannon Research Institute at HCA HealthONE Presbyterian St. Luke's
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New York
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New York, New York, Estados Unidos, 10029
- Ainda não está recrutando
- Icahn School of Medicine at Mount Sinai - Oncology
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Texas
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Irving, Texas, Estados Unidos, 75039
- Recrutamento
- NEXT Dallas - Oncology Department
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San Antonio, Texas, Estados Unidos, 78229
- Recrutamento
- START | San Antonio
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Uusimaa
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Helsinki, Uusimaa, Finlândia, 00029
- Ainda não está recrutando
- HUS-Yhtymä, Helsingin yliopistollinen sairaala (HUS) - Syöpäkeskus
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North Holland
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Amsterdam, North Holland, Holanda, 1066 CX
- Ainda não está recrutando
- Nederlands Kanker Instituut
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Roma, Itália, 00128
- Ainda não está recrutando
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Fase I
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Stockholm County
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Stockholm, Stockholm County, Suécia, 171 76
- Ainda não está recrutando
- Karolinska Universitetssjukhuset - Solna - Fas I-enheten Solna CKC
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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:
- KRAS G12D mutated solid tumor
- Participant must be ≥18 years old or the legal age of consent in the jurisdiction in which the study is taking place when signing the screening ICF
- At least one measurable lesion as per RECIST v1.1. outside the CNS
- Eastern Cooperative Oncology Group performance status (ECOG PS) of ≤1
- Male or Female: Contraceptive use by participant or participant's partners should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- Life expectancy of at least 3 months in the opinion of the Investigator
- Histologically/pathologically documented diagnosis of advanced/metastatic adenocarcinoma of the colon and rectum.
- Adequate hematologic and end-organ function
Exclusion Criteria:
- Leptomeningeal disease or carcinomatous meningiti
- Uncontrolled and/or active/symptomatic brain metastases.
- Significant traumatic injury or major surgical procedure within 4 weeks of first dose of study intervention
- Known hypersensitivity to any component of study intervention
- Previous (within 3 years) or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in the respective substudy.
- Active infection requiring systemic anti-infective therapy within 14 days of first dose of study intervention
- Known HIV infection
- Active Hepatitis B virus (HBV) infection
- Active Hepatitis C virus (HCV) infection
- Significant cardiac disorder
- History of risk factors for torsade de pointes (TdP) (e.g., heart failure, family history of long QT syndrome)
- Participants with inadequately managed diabetes as assessed by the Investigator
- Toxicities from prior anticancer therapy, defined as not having resolved to Grade ≤1 or as specified in the respective substudy protocol as per NCI CTCAE v.6.0 with the following exceptions: Alopecia of any grade, Peripheral neuropathy Grade ≤2, Autoimmune endocrine disorders Grade ≤2 managed with stable endocrine replacement therapy
- History of (non-infectious) pneumonitis/interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis (unless it has resolved without sequelae without use of steroids), or any evidence of clinically-active pneumonitis/ILD
- History of the following eye disorders: keratitis, ulcerative keratitis
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: N / D
- Modelo Intervencional: Atribuição sequencial
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
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Experimental: Dosage escalation
In the dosage escalation part, different dose levels of BAY 3771249 administered as monotherapy and in combination with cetuximab are planned. |
Oral Intravenous (IV) infusion |
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Experimental: Dosage expansion
In the dosage expansion part, participants will receive BAY 3771249 either as monotherapy or in combination with cetuximab until disease progression as defined by RECIST v1.1, the occurrence of unacceptable toxicity, or the fulfillment of any other withdrawal criteria. |
Oral Intravenous (IV) infusion |
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Change from baseline in laboratory test results
Prazo: Up to approximately 2 years
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Hematology, serum chemistry, urinalysis and coagulation tests. Applicable in Dosage escalation and expansion |
Up to approximately 2 years
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Change from baseline in vital signs: Blood pressure
Prazo: Up to approximately 2 years
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Applicable in Dosage escalation and expansion |
Up to approximately 2 years
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Change from baseline in vital signs: Body temperature
Prazo: Up to approximately 2 years
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Applicable in Dosage escalation and expansion |
Up to approximately 2 years
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Change from baseline in vital signs: Oxygen saturation
Prazo: Up to approximately 2 years
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Applicable in Dosage escalation and expansion |
Up to approximately 2 years
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Change from baseline in vital signs: Pulse rate
Prazo: Up to approximately 2 years
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Applicable in Dosage escalation and expansion |
Up to approximately 2 years
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Change from baseline in vital signs: Respiratory rate
Prazo: Up to approximately 2 years
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Applicable in Dosage escalation and expansion |
Up to approximately 2 years
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Number of participants experiencing a dose-limiting toxicity (DLT) at each dosage
Prazo: Up to approximately 3 weeks
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Applicable in Dose escalation part |
Up to approximately 3 weeks
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Number of participants with Treatment-emergent adverse events (TEAEs)
Prazo: Up to approximately 2 years.
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Applicable in Dosage escalation and expansion |
Up to approximately 2 years.
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Objective response rate (ORR) as determined by the Investigator according to RECIST v1.1
Prazo: Up to approximately 2 years
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Applicable in Dosage escalation and expansion |
Up to approximately 2 years
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Severity of TEAEs
Prazo: Up to approximately 2 years.
|
Applicable in Dosage escalation and expansion |
Up to approximately 2 years.
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Pharmacokinetics (PK) parameters such as area under the concentration vs time curve (AUC)
Prazo: Up to approximately 2 years
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Applicable in Dosage escalation |
Up to approximately 2 years
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PK parameters such as maximum observed drug concentration (Cmax)
Prazo: Up to approximately 2 years
|
Applicable in Dosage escalation |
Up to approximately 2 years
|
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
Outros números de identificação do estudo
- 23111-1
- 2025 (Concessão/Contrato do NIH dos EUA)
- 2025-523648-11-00 (Ctis)
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
Descrição do plano IPD
Currently, there is no established plan for the sharing of Individual Patient Data (IPD) from this study. The availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA 'Principles for responsible clinical trial data sharing.' This pertains to the scope, timepoint, and process of data access. As such, Bayer commits to considering requests from qualified researchers for patient- / study-level clinical trial data, and documents from clinical trials involving medicines and indications approved in the US and EU. However, this commitment does not reflect an active IPD sharing plan. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Researchers can use www.vivli.org to request access to IPD and documents from clinical studies to conduct research. Information on Bayer's criteria for listing studies is provided in the member section of the portal.
Informações sobre medicamentos e dispositivos, documentos de estudo
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Estuda um produto de dispositivo regulamentado pela FDA dos EUA
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