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A Study of GFH276 Combined With Cetuximab or Chemotherapy in Participants With Solid Tumors and Pancreatic Ductal Adenocarcinoma (PDAC) Harboring RAS Mutation

30 de setembro de 2026 atualizado por: Genfleet Therapeutics (Shanghai) Inc.

A Multi-center, Open-label Phase Ib/II Study Exploring the Safety/Tolerability, Pharmacokinetics, and Efficacy of GFH276 in Combination With Cetuximab or Chemotherapy in the Treatment of Patients With Advanced Solid Tumors and Pancreatic Ductal Adenocarcinoma (PDAC) Harboring RAS Mutation

A Study of GFH276 Combined With Cetuximab or Chemotherapy in Participants With Solid Tumors and Pancreatic Ductal Adenocarcinoma (PDAC) Harboring RAS Mutation

Visão geral do estudo

Status

Recrutamento

Condições

Intervenção / Tratamento

Descrição detalhada

This is an open-label, multicenter Phase Ib/II clinical trial to evaluate the safety, tolerability, and preliminary anti-tumor efficacy of oral GFH276 in combination with cetuximab or standard chemotherapy in adult patients with locally advanced or metastatic RAS-mutated solid tumors and pancreatic ductal adenocarcinoma (PDAC).

Participants will be enrolled into three treatment arms with different combination regimens.

In the Phase Ib stage, dose escalation of GFH276 will be performed in each combination arm to identify the optimal recommended Phase 2 dose (RP2D) based on dose-limiting toxicity (DLT) and the overall safety profile. After RP2D determination, Phase II expansion cohorts will enroll eligible patients to further evaluate the anti-tumor efficacy and long-term safety of each combination regimen. Study-related assessments will include tumor imaging, laboratory tests, adverse event monitoring, and pharmacokinetic sampling throughout the treatment period.

Participants will continue their assigned study treatment until confirmed disease progression, intolerable toxicity, withdrawal of consent, or study closure.

Tipo de estudo

Intervencional

Inscrição (Estimado)

222

Estágio

  • Fase 2
  • Fase 1

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Contato de estudo

Estude backup de contato

Locais de estudo

  • Austrália
    • New South Wales
      • Concord, New South Wales, Austrália, 2139
        • Ainda não está recrutando
        • Concord Cancer Centre, Concord Repatriation General Hospital, Sydney Local Health District
        • Contato:
      • North Ryde, New South Wales, Austrália, 2109
        • Recrutamento
        • Macquarie University / Clinical Trials Unit
        • Contato:
          • PhD
        • Contato:
    • South Australia
      • Woodville South, South Australia, Austrália, 5011
        • Ainda não está recrutando
        • The Queen Elizabeth Hospital
        • Contato:
    • Victoria
      • Clayton, Victoria, Austrália, 3168
        • Recrutamento
        • Monash Health (Monash Medical Centre)
        • Contato:
      • Epping, Victoria, Austrália, 3076
        • Ainda não está recrutando
        • Northern Health
        • Contato:
      • Frankston, Victoria, Austrália, 3199
        • Recrutamento
        • PASO Medical
        • Contato:
          • Vinod Ganju, MBBS
          • Número de telefone: 0397815244
          • E-mail: vg@paso.com.au
  • China
    • Beijing Municipality
      • Beijing, Beijing Municipality, China, 100730
        • Recrutamento
        • Peking Union Medical College Hospital
        • Contato:
          • Chunmei Bai, MD
    • Guangdong
      • Guangzhou, Guangdong, China, 510120
        • Recrutamento
        • Sun Yat-sen Memorial Hospital, Sun Yat-sen University
        • Contato:
          • Zhihua Li, MD
    • Heilongjiang
      • Harbin, Heilongjiang, China, 150081
        • Ainda não está recrutando
        • The Third Affiliated Hospital (Cancer Hospital) of Harbin Medical University
        • Contato:
          • Guangyu Wang, MD
    • Henan
      • Zhengzhou, Henan, China, 450052
        • Recrutamento
        • The First Affiliated Hospital of Zhengzhou University
        • Contato:
          • Hong Zong, MD
    • Hubei
      • Wuhan, Hubei, China, 430022
        • Ainda não está recrutando
        • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
        • Contato:
          • Heshui Wu, MD
    • Liaoning
      • Shenyang, Liaoning, China, 110001
        • Ainda não está recrutando
        • The First Affiliated Hospital of China Medical University
        • Contato:
          • Xiujuan Qu, MD
    • Shaanxi
      • Xi'an, Shaanxi, China, 710061
        • Ainda não está recrutando
        • The First Affiliated Hospital of Xi'an Jiaotong University
        • Contato:
          • Yinying Wu, MD
    • Shandong
      • Jinan, Shandong, China, 250117
        • Recrutamento
        • Shandong First Medical University Affiliated Tumor Hospital
        • Contato:
          • Shuqin Ni, MD
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, China, 200032
        • Recrutamento
        • Fudan University Shanghai Cancer Center
        • Contato:
    • Sichuan
      • Chengdu, Sichuan, China, 610041
        • Recrutamento
        • West China Hospital of Sichuan University
        • Contato:
          • Xuelei Ma, MD
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310016
        • Recrutamento
        • Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
        • Contato:
          • Da Li, MD

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

18 anos e mais velhos (Adulto, Adulto mais velho)

Aceita Voluntários Saudáveis

Não

Gêneros Elegíveis para o Estudo

Tudo

Descrição

Inclusion Criteria:

  1. Age ≥ 18 years
  2. Histologically or cytologically confirmed locally advanced or metastatic solid tumor and PDAC with RAS mutation or KRAS amplification
  3. At least one measurable lesion according to RECIST v1.1
  4. ECOG performance status 0 or 1
  5. Life expectancy > 3 months
  6. Adequate organ function
  7. Willing to provide written informed consent
  8. Fertile participants must use effective contraception

Exclusion Criteria:

  1. Other active malignancy within 3 years
  2. Symptomatic brain metastases, leptomeningeal disease, spinal cord compression, or primary brain tumor
  3. History of active clinically significant cardiovascular dysfunction
  4. For participants with known concomitant second oncodriver for PDAC or for solid tumors.
  5. With active infection (HIV, HBV, HCV, syphilis)
  6. The presence of clinical or radiological evidence of intestinal obstruction.
  7. Prior anticancer therapy within 28 days or 5 half-lives
  8. Diagnosis of deep vein thrombosis or pulmonary embolism within 3 months
  9. Hypersensitivity to study drugs, or inability to swallow tablets or comply with study procedures.
  10. History of central nervous system (CNS)disease
  11. Presence of clinically significant interstitial lung disease, radiation pneumonitis, or immune-related pneumonia that requires treatment.
  12. With uncontrollable or symptomatic pleural effusion, ascites, or pericardial effusion.

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

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: Arm A: GFH276 + Cetuximab

GFH276 once daily; cetuximab 500 mg/m² intravenous infusion every 2 weeks.
Medicamento: GFH276

Oral GFH276 administered once daily in combination with other study drugs.

Medicamento: Cetuximab

Intravenous cetuximab at a dose of 500 mg/m²
Experimental: Arm B: GFH276 + AG

GFH276 once daily; nab-paclitaxel 125 mg/m² + gemcitabine 1000 mg/m² (AG regimen); 4-week cycle (D1, D8, D15) or 3-week cycle (D1, D8) in China
Medicamento: GFH276

Oral GFH276 administered once daily in combination with other study drugs.

Medicamento: Nab paclitaxel

Intravenous nab-paclitaxel at a dose of 125 mg/m².

Medicamento: Gemcitabine

Intravenous Gemcitabine at a dose of 1000 mg/m².
Experimental: Arm C: GFH276 + mFOLFIRINOX

GFH276 once daily; mFOLFIRINOX :Fluorouracil 2400 mg/m²(46 h), Leucovorin 400 mg/m², Irinotecan 150 mg/m², Oxaliplatin 85 mg/m², IV D1, every 2 weeks .

The mFOLFIRINOX regimen may be administered per the above dosage, or in accordance with national or institutional guidelines.
Medicamento: GFH276

Oral GFH276 administered once daily in combination with other study drugs.

Medicamento: Fluorouracil

Intravenous Fluorouracil at a dose of 2400 mg/m² via 46-hour infusion.Dosing may follow the above regimen or local institutional standards.

Medicamento: Leucovorin

Intravenous leucovorin at a dose of 400 mg/m².Dosing may follow the above regimen or local institutional standards.

Medicamento: Irinotecan

Intravenous irinotecan at a dose of 150 mg/m².Dosing may follow the above regimen or local institutional standards.

Medicamento: Oxaliplatin

Intravenous oxaliplatin at a dose of 85 mg/m².Dosing may follow the above regimen or local institutional standards.

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Phase Ib:Incidence of Dose-Limiting Toxicity (DLT) Events
Prazo: First 28 days (21 days for AG （3-week cycle）)

The incidence of DLT events
First 28 days (21 days for AG （3-week cycle）)
Phase Ib:Incidence and Severity of Adverse Events (AE) and Serious Adverse Events (SAE)
Prazo: From the first dose until 30 days after the last dose, assessed up to 24 months

The incidence and severity of AEs and SAEs，according to NCI CTCAE，v6.0
From the first dose until 30 days after the last dose, assessed up to 24 months
Phase II:Objective Response Rate (ORR)
Prazo: From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months

Assessed by investigators according to RECIST 1.1
From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Phase Ib: Number of participants with abnormality in hematology laboratory parameters
Prazo: up to 24 months

Number of participants with abnormality in hematology laboratory parameters，Hematology assessments will include hemoglobin, white blood cell count, differential white blood cell counts and platelet count
up to 24 months
Phase Ib: Number of participants with abnormality in clinical chemistry laboratory assessments
Prazo: up to 24 months

Number of participants with abnormality in clinical chemistry laboratory assessments， assessments will include serum chemistry (such as sodium, potassium, urea, creatinine) and liver function parameters, including alanine aminotransferase (ALT), aspartate aminotransferase (AST) and bilirubin.
up to 24 months
Phase Ib: Number of participants with abnormality in body temperature
Prazo: up to 24 months

Number of participants with abnormality in body temperature(°C), throughout the study.
up to 24 months
Phase Ib: Number of participants with abnormality in blood pressure
Prazo: up to 24 months

Number of participants with abnormality in blood pressure, including systolic blood pressure (mmHg) and diastolic blood pressure (mmHg)
up to 24 months
Phase Ib: Number of participants with abnormality in Physical Examination Findings
Prazo: up to 24 months

Number of participants with abnormality in Physical Examination Findings
up to 24 months
Phase Ib: Number of participants with abnormality in PR interval
Prazo: up to 24 months

Number of participants with abnormality in electrocardiogram (ECG) parameters, including PR interval
up to 24 months
Phase Ib: Number of participants with abnormality in corrected QT interval using Frederica's formula (QTcF)
Prazo: up to 24 months

Number of participants with abnormality incorrected QT interval using Frederica's formula (QTcF)
up to 24 months

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Phase II: Incidence and Severity of AE and SAE
Prazo: From the first dose until 30 days after the last dose, assessed up to 24 months

Incidence and Severity of AE and SAE，Assessed according to CTCAE 6.0
From the first dose until 30 days after the last dose, assessed up to 24 months
DCR
Prazo: From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months

Disease Control Rate (DCR)
From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
DoR
Prazo: From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months

Duration of Response assessed by investigators
From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
TTR
Prazo: From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months

Time To Response assessed by investigators
From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
PFS
Prazo: From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months

Progression-Free Survival (PFS) per Response Evaluation Criteria according to RECIST 1.1, as Determined by investigators
From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
OS
Prazo: From the first dose until date of death from any cause, assessed up to 24 months

Overall Survival
From the first dose until date of death from any cause, assessed up to 24 months
Time to peak plasma concentration（Tmax） of GFH276
Prazo: up to 6 months

Plasma concentrations of GFH276 and relevant pharmacokinetic parameters including Tmax were evaluated.
up to 6 months
Maximum plasma concentration of GFH276
Prazo: up to 6 months

Plasma concentrations of GFH276 and relevant pharmacokinetic parameters including Cmax were evaluated.
up to 6 months
Area Under the Curve from time zero to 24 hours of GFH276
Prazo: up to 6 months

Plasma concentrations of GFH276 and relevant pharmacokinetic parameters including AUC0-24 were evaluated.
up to 6 months

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

Genfleet Therapeutics (Shanghai) Inc.

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Estimado)

1 de setembro de 2026

Conclusão Primária (Estimado)

1 de novembro de 2027

Conclusão do estudo (Estimado)

1 de setembro de 2028

Datas de inscrição no estudo

Enviado pela primeira vez

9 de junho de 2026

Enviado pela primeira vez que atendeu aos critérios de CQ

24 de junho de 2026

Primeira postagem (Real)

1 de julho de 2026

Atualizações de registro de estudo

Última Atualização Postada (Real)

5 de outubro de 2026

Última atualização enviada que atendeu aos critérios de controle de qualidade

30 de setembro de 2026

Última verificação

1 de setembro de 2026

Mais Informações

Termos relacionados a este estudo

Palavras-chave

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • GFH276X0201

Plano para dados de participantes individuais (IPD)

Planeja compartilhar dados de participantes individuais (IPD)?

NÃO

Informações sobre medicamentos e dispositivos, documentos de estudo

Estuda um medicamento regulamentado pela FDA dos EUA

Não

Estuda um produto de dispositivo regulamentado pela FDA dos EUA

Não

produto fabricado e exportado dos EUA

Não

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

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