A Phase Ib/II Study of GFH276 in Combination With Chemotherapy (± Bevacizumab) or Cetuximab in Patients With RAS-mutant Metastatic Colorectal Cancer (A Phase Ib/II)
An Open-label, Multicenter, Phase Ib/II Study to Evaluate the Safety/Tolerability, Efficacy, and Pharmacokinetic Characteristics of GFH276 in Combination With Chemotherapy (+/- Bevacizumab) or Cetuximab in Patients With RAS-mutant Metastatic Colorectal Cancer
This is a Phase Ib/II study to explore the safety/tolerability, efficacy, and pharmacokinetic (PK) characteristics of GFH276 in combination with chemotherapy (+/- bevacizumab) or cetuximab in patients with RAS-mutant metastatic colorectal cancer (mCRC).
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Descrição detalhada
This is a multicenter, open-label, Phase Ib/II study to evaluate the safety/tolerability, efficacy, and PK characteristics of GFH276 in combination with chemotherapy (+/- bevacizumab) or cetuximab in patients with RAS-mutant mCRC. The study includes a Phase Ib dose-escalation part and a Phase II part.
Cohort 1 is an open-label, multicenter study to evaluate GFH276 in combination with FOLFIRI±bev in patients with RAS-mutant metastatic colorectal cancer.
Cohort 2 is an open-label, multicenter study to evaluate GFH276 in combination with mFOLFOX6±bev in patients with RAS-mutant metastatic colorectal cancer.
Cohort 3 is an open-label, multicenter study to evaluate GFH276 in combination with Cetuximab in patients with RAS-mutant metastatic colorectal cancer.
Cohort A is an open-label, multicenter study to evaluate GFH276 in combination with FOLFIRI or mFOLFOX6±bev in patients with RAS-mutant metastatic colorectal cancer.
Cohort B is an open-label, multicenter study to evaluate GFH276 in combination with Cetuximab in patients with RAS-mutant metastatic colorectal cancer.
Cohort C is an open-label, multicenter study to evaluate FOLFIRI or mFOLFOX6+bev in patients with RAS-mutant metastatic colorectal cancer.
Tipo de estudo
Inscrição (Estimado)
Estágio
- Fase 2
- Fase 1
Contactos e Locais
Contato de estudo
- Nome: yuting peng, PM
- Número de telefone: 13730813620
- E-mail: ytpeng@genfleet.com
Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Inclusion Criteria:
- Subjects must voluntarily agree to participate in the trial and sign a written informed consent form.
- Male or female ≥ 18 years old and ≤75 years old.
- Histologically confirmed metastatic colorectal cancer (mCRC)
- Participants must have experienced disease progression or recurrence during or after prior standard therapy.
- Participants enrolled in this study must provide a written test report confirming RAS mutation or KRAS amplification
- ECOG performance status of 0-1.
- With a life expectancy of ≥12 weeks
- Participants must have at least one measurable lesion other than brain lesions per RECIST 1.1.
- Adequate laboratory parameters during the screening period.
Exclusion Criteria:
- Active brain metastases.
- Known concomitant other targetable driver gene alterations, including but not limited to HER2, BRAF V600E, etc
- Prior treatment with a PAN-RAS inhibitor.
3. Palliative radiotherapy was completed within 28 days before the first dose. 4. Have poorly controlled or severe Gastrointestinal disease. 5. Subjects with active hepatitis B or active hepatitis C. 6. Known allergies to the study drug or its components. 7. Pregnant or lactating women.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Não randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
|
Experimental: Phase I:Cohort 1
GFH276+FOLFIRI±bev IV, |
Phase Ib - Dose Escalation Cohort 1 GFH276 in combination with FOLFIRI±bev, (bevacizumab): Irinotecan 、Leucovorin ， Fluorouracil ，
Outros nomes:
Phase Ib - Dose Escalation Cohort 2 GFH276, QD. in combination with mFOLFOX6±bev, mFOLFOX6: Oxaliplatin, Leucovorin, Fluorouracil bev (bevacizumab)
Outros nomes:
Phase II Cohort B：GFH276, oral, QD + Cetuximab, Cetuximab:
Outros nomes:
Phase II Cohort A：GFH276, oral +FOLFIRI/mFOLFOX6±bev, IV, Q4W, d1,d15
Outros nomes:
Phase Ib - Dose Escalation Cohort 3：GFH276 in combination with cetuximab， Cetuximab:
Outros nomes:
|
|
Experimental: Phase I:Cohort 2
GFH276+ mFOLFOX6±bev IV, |
Phase Ib - Dose Escalation Cohort 1 GFH276 in combination with FOLFIRI±bev, (bevacizumab): Irinotecan 、Leucovorin ， Fluorouracil ，
Outros nomes:
Phase Ib - Dose Escalation Cohort 2 GFH276, QD. in combination with mFOLFOX6±bev, mFOLFOX6: Oxaliplatin, Leucovorin, Fluorouracil bev (bevacizumab)
Outros nomes:
Phase II Cohort B：GFH276, oral, QD + Cetuximab, Cetuximab:
Outros nomes:
Phase II Cohort A：GFH276, oral +FOLFIRI/mFOLFOX6±bev, IV, Q4W, d1,d15
Outros nomes:
Phase Ib - Dose Escalation Cohort 3：GFH276 in combination with cetuximab， Cetuximab:
Outros nomes:
|
|
Experimental: Phase I:Cohort 3
Cetuximab IV, |
Phase Ib - Dose Escalation Cohort 1 GFH276 in combination with FOLFIRI±bev, (bevacizumab): Irinotecan 、Leucovorin ， Fluorouracil ，
Outros nomes:
Phase Ib - Dose Escalation Cohort 2 GFH276, QD. in combination with mFOLFOX6±bev, mFOLFOX6: Oxaliplatin, Leucovorin, Fluorouracil bev (bevacizumab)
Outros nomes:
Phase II Cohort B：GFH276, oral, QD + Cetuximab, Cetuximab:
Outros nomes:
Phase II Cohort A：GFH276, oral +FOLFIRI/mFOLFOX6±bev, IV, Q4W, d1,d15
Outros nomes:
Phase Ib - Dose Escalation Cohort 3：GFH276 in combination with cetuximab， Cetuximab:
Outros nomes:
|
|
Experimental: Phase II:Cohort A
GFH276, oral, QD +FOLFIRI/mFOLFOX6±bev, IV, |
Phase Ib - Dose Escalation Cohort 1 GFH276 in combination with FOLFIRI±bev, (bevacizumab): Irinotecan 、Leucovorin ， Fluorouracil ，
Outros nomes:
Phase Ib - Dose Escalation Cohort 2 GFH276, QD. in combination with mFOLFOX6±bev, mFOLFOX6: Oxaliplatin, Leucovorin, Fluorouracil bev (bevacizumab)
Outros nomes:
Phase II Cohort B：GFH276, oral, QD + Cetuximab, Cetuximab:
Outros nomes:
Phase II Cohort A：GFH276, oral +FOLFIRI/mFOLFOX6±bev, IV, Q4W, d1,d15
Outros nomes:
Phase Ib - Dose Escalation Cohort 3：GFH276 in combination with cetuximab， Cetuximab:
Outros nomes:
|
|
Experimental: Phase II:Cohort B
GFH276, oral, +Cetuximab, IV, |
Phase Ib - Dose Escalation Cohort 1 GFH276 in combination with FOLFIRI±bev, (bevacizumab): Irinotecan 、Leucovorin ， Fluorouracil ，
Outros nomes:
Phase Ib - Dose Escalation Cohort 2 GFH276, QD. in combination with mFOLFOX6±bev, mFOLFOX6: Oxaliplatin, Leucovorin, Fluorouracil bev (bevacizumab)
Outros nomes:
Phase II Cohort B：GFH276, oral, QD + Cetuximab, Cetuximab:
Outros nomes:
Phase II Cohort A：GFH276, oral +FOLFIRI/mFOLFOX6±bev, IV, Q4W, d1,d15
Outros nomes:
Phase Ib - Dose Escalation Cohort 3：GFH276 in combination with cetuximab， Cetuximab:
Outros nomes:
|
|
Comparador Ativo: Phase II:Cohort C
FOLFIRI/mFOLFOX6+bev, IV |
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Phase Ib: Incidence and severity of AEs and SAEs
Prazo: up to 24 months
|
Incidence and severity of AEs and SAEs |
up to 24 months
|
|
Phase Ib: The incidence of DLT events: The incidence of DLT events
Prazo: First 28 days
|
The incidence of DLT events |
First 28 days
|
|
Phase II: Objective response rate （ORR）
Prazo: From first use of medication to disease progression，up to 24 months
|
Overall Response Rate assessed by investigators according to RECIST 1.1 |
From first use of medication to disease progression，up to 24 months
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
ORR:
Prazo: From first use of medication to disease progression，up to 24 months
|
Overall Response Rate assessed by investigators according to RECIST 1.1 |
From first use of medication to disease progression，up to 24 months
|
|
OS
Prazo: From first use of medication to disease progression，up to 24 months
|
Overall Survival |
From first use of medication to disease progression，up to 24 months
|
|
Cmax
Prazo: From first use of medication to C6，up to 6 months
|
Maximum plasma concentration |
From first use of medication to C6，up to 6 months
|
|
DOR
Prazo: From first use of medication to disease progression，up to 24 months
|
Duration of Response assessed by investigators |
From first use of medication to disease progression，up to 24 months
|
|
DCR
Prazo: From first use of medication to disease progression，up to 24 months
|
Disease Control Rate |
From first use of medication to disease progression，up to 24 months
|
|
TTR
Prazo: From first use of medication to disease progression，up to 24 months
|
Time To Response assessed by investigators |
From first use of medication to disease progression，up to 24 months
|
|
PFS
Prazo: From first use of medication to disease progression，up to 24 months
|
Progression-Free Survival assessed by investigators according to RECIST 1.1 |
From first use of medication to disease progression，up to 24 months
|
|
Tmax
Prazo: From first use of medication to C6，up to 6 months
|
Time to Maximum Concentration |
From first use of medication to C6，up to 6 months
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: ruihua xu, MD, Sun Yat-Sen University Cancer Center
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Estimado)
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
Palavras-chave
Termos MeSH relevantes adicionais
- Aminoácidos, peptídeos e proteínas
- Proteínas
- Produtos químicos orgânicos
- Compostos heterocíclicos, 1 anel
- Compostos heterocíclicos
- Compostos heterocíclicos, 2 anel
- Compostos heterocíclicos, anel fundido
- Camptothecin
- Alcalóides
- Enzimas e coenzimas
- Anticorpos, monoclonais, humanizados
- Anticorpos, monoclonais
- Anticorpos
- Imunoglobulinas
- Imunoproteínas
- Proteínas sanguíneas
- Globulinas de soro
- Globulins
- Complexos de coordenação
- Pirimidinas
- Formiltetra -hidrofolatos
- Tetra -hidrofolatos
- Ácido fólico
- Pterins
- Pteridinas
- Uracil
- Pirimidinonas
- Coenzimas
- Oxaliplatina
- Bevacizumabe
- Irinotecano
- Cetuximabe
- Fluorouracila
- Leucovorina
Outros números de identificação do estudo
- GFH276X1202
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
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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