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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

2026年9月30日 更新者：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

研究概览

地位

招聘中

条件

干预/治疗

详细说明

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.

研究类型

介入性

注册 (估计的)

222

阶段

  • 阶段2
  • 阶段1

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习联系方式

研究联系人备份

学习地点

  • 中国
    • Beijing Municipality
      • Beijing、Beijing Municipality、中国、100730
        • 招聘中
        • Peking Union Medical College Hospital
        • 接触：
          • Chunmei Bai, MD
    • Guangdong
      • Guangzhou、Guangdong、中国、510120
        • 招聘中
        • Sun Yat-sen Memorial Hospital, Sun Yat-sen University
        • 接触：
          • Zhihua Li, MD
    • Heilongjiang
      • Harbin、Heilongjiang、中国、150081
        • 尚未招聘
        • The Third Affiliated Hospital (Cancer Hospital) of Harbin Medical University
        • 接触：
          • Guangyu Wang, MD
    • Henan
      • Zhengzhou、Henan、中国、450052
        • 招聘中
        • The First Affiliated Hospital of Zhengzhou University
        • 接触：
          • Hong Zong, MD
    • Hubei
      • Wuhan、Hubei、中国、430022
        • 尚未招聘
        • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
        • 接触：
          • Heshui Wu, MD
    • Liaoning
      • Shenyang、Liaoning、中国、110001
        • 尚未招聘
        • The First Affiliated Hospital of China Medical University
        • 接触：
          • Xiujuan Qu, MD
    • Shaanxi
      • Xi'an、Shaanxi、中国、710061
        • 尚未招聘
        • The First Affiliated Hospital of Xi'an Jiaotong University
        • 接触：
          • Yinying Wu, MD
    • Shandong
      • Jinan、Shandong、中国、250117
        • 招聘中
        • Shandong First Medical University Affiliated Tumor Hospital
        • 接触：
          • Shuqin Ni, MD
    • Shanghai Municipality
      • Shanghai、Shanghai Municipality、中国、200032
        • 招聘中
        • Fudan University Shanghai Cancer Center
        • 接触：
    • Sichuan
      • Chengdu、Sichuan、中国、610041
        • 招聘中
        • West China Hospital of Sichuan University
        • 接触：
          • Xuelei Ma, MD
    • Zhejiang
      • Hangzhou、Zhejiang、中国、310016
        • 招聘中
        • Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
        • 接触：
          • Da Li, MD
  • 澳大利亚
    • New South Wales
      • Concord、New South Wales、澳大利亚、2139
        • 尚未招聘
        • Concord Cancer Centre, Concord Repatriation General Hospital, Sydney Local Health District
        • 接触：
      • North Ryde、New South Wales、澳大利亚、2109
        • 招聘中
        • Macquarie University / Clinical Trials Unit
        • 接触：
          • PhD
        • 接触：
    • South Australia
      • Woodville South、South Australia、澳大利亚、5011
        • 尚未招聘
        • The Queen Elizabeth Hospital
        • 接触：
    • Victoria
      • Clayton、Victoria、澳大利亚、3168
        • 招聘中
        • Monash Health (Monash Medical Centre)
        • 接触：
      • Epping、Victoria、澳大利亚、3076
        • 尚未招聘
        • Northern Health
        • 接触：
      • Frankston、Victoria、澳大利亚、3199
        • 招聘中
        • PASO Medical
        • 接触：

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 及以上 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

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.

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：非随机化
  • 介入模型：并行分配
  • 屏蔽：无（打开标签）

武器和干预

参与者组/臂
干预/治疗
实验性的：Arm A: GFH276 + Cetuximab

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

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

药品：Cetuximab

Intravenous cetuximab at a dose of 500 mg/m²
实验性的：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
药品：GFH276

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

药品：Nab paclitaxel

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

药品：Gemcitabine

Intravenous Gemcitabine at a dose of 1000 mg/m².
实验性的：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.
药品：GFH276

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

药品：Fluorouracil

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

药品：Leucovorin

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

药品：Irinotecan

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

药品：Oxaliplatin

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

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Phase Ib:Incidence of Dose-Limiting Toxicity (DLT) Events
大体时间：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)
大体时间：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)
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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)
大体时间：up to 24 months

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

次要结果测量

结果测量
措施说明
大体时间
Phase II: Incidence and Severity of AE and SAE
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：up to 6 months

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

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Genfleet Therapeutics (Shanghai) Inc.

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (估计的)

2026年9月1日

初级完成 (估计的)

2027年11月1日

研究完成 (估计的)

2028年9月1日

研究注册日期

首次提交

2026年6月9日

首先提交符合 QC 标准的

2026年6月24日

首次发布 (实际的)

2026年7月1日

研究记录更新

最后更新发布 (实际的)

2026年10月5日

上次提交的符合 QC 标准的更新

2026年9月30日

最后验证

2026年9月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • GFH276X0201

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

不

药物和器械信息、研究文件

研究美国 FDA 监管的药品

不

研究美国 FDA 监管的设备产品

不

在美国制造并从美国出口的产品

不

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