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).
研究概览
详细说明
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.
研究类型
注册 (估计的)
阶段
- 阶段2
- 阶段1
联系人和位置
学习联系方式
- 姓名：yuting peng, PM
- 电话号码：13730813620
- 邮箱：ytpeng@genfleet.com
参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
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.
学习计划
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：Phase I:Cohort 1
GFH276+FOLFIRI±bev IV, |
Phase Ib - Dose Escalation Cohort 1 GFH276 in combination with FOLFIRI±bev, (bevacizumab): Irinotecan 、Leucovorin ， Fluorouracil ，
其他名称：
Phase Ib - Dose Escalation Cohort 2 GFH276, QD. in combination with mFOLFOX6±bev, mFOLFOX6: Oxaliplatin, Leucovorin, Fluorouracil bev (bevacizumab)
其他名称：
Phase II Cohort B：GFH276, oral, QD + Cetuximab, Cetuximab:
其他名称：
Phase II Cohort A：GFH276, oral +FOLFIRI/mFOLFOX6±bev, IV, Q4W, d1,d15
其他名称：
Phase Ib - Dose Escalation Cohort 3：GFH276 in combination with cetuximab， Cetuximab:
其他名称：
|
|
实验性的：Phase I:Cohort 2
GFH276+ mFOLFOX6±bev IV, |
Phase Ib - Dose Escalation Cohort 1 GFH276 in combination with FOLFIRI±bev, (bevacizumab): Irinotecan 、Leucovorin ， Fluorouracil ，
其他名称：
Phase Ib - Dose Escalation Cohort 2 GFH276, QD. in combination with mFOLFOX6±bev, mFOLFOX6: Oxaliplatin, Leucovorin, Fluorouracil bev (bevacizumab)
其他名称：
Phase II Cohort B：GFH276, oral, QD + Cetuximab, Cetuximab:
其他名称：
Phase II Cohort A：GFH276, oral +FOLFIRI/mFOLFOX6±bev, IV, Q4W, d1,d15
其他名称：
Phase Ib - Dose Escalation Cohort 3：GFH276 in combination with cetuximab， Cetuximab:
其他名称：
|
|
实验性的：Phase I:Cohort 3
Cetuximab IV, |
Phase Ib - Dose Escalation Cohort 1 GFH276 in combination with FOLFIRI±bev, (bevacizumab): Irinotecan 、Leucovorin ， Fluorouracil ，
其他名称：
Phase Ib - Dose Escalation Cohort 2 GFH276, QD. in combination with mFOLFOX6±bev, mFOLFOX6: Oxaliplatin, Leucovorin, Fluorouracil bev (bevacizumab)
其他名称：
Phase II Cohort B：GFH276, oral, QD + Cetuximab, Cetuximab:
其他名称：
Phase II Cohort A：GFH276, oral +FOLFIRI/mFOLFOX6±bev, IV, Q4W, d1,d15
其他名称：
Phase Ib - Dose Escalation Cohort 3：GFH276 in combination with cetuximab， Cetuximab:
其他名称：
|
|
实验性的：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 ，
其他名称：
Phase Ib - Dose Escalation Cohort 2 GFH276, QD. in combination with mFOLFOX6±bev, mFOLFOX6: Oxaliplatin, Leucovorin, Fluorouracil bev (bevacizumab)
其他名称：
Phase II Cohort B：GFH276, oral, QD + Cetuximab, Cetuximab:
其他名称：
Phase II Cohort A：GFH276, oral +FOLFIRI/mFOLFOX6±bev, IV, Q4W, d1,d15
其他名称：
Phase Ib - Dose Escalation Cohort 3：GFH276 in combination with cetuximab， Cetuximab:
其他名称：
|
|
实验性的：Phase II:Cohort B
GFH276, oral, +Cetuximab, IV, |
Phase Ib - Dose Escalation Cohort 1 GFH276 in combination with FOLFIRI±bev, (bevacizumab): Irinotecan 、Leucovorin ， Fluorouracil ，
其他名称：
Phase Ib - Dose Escalation Cohort 2 GFH276, QD. in combination with mFOLFOX6±bev, mFOLFOX6: Oxaliplatin, Leucovorin, Fluorouracil bev (bevacizumab)
其他名称：
Phase II Cohort B：GFH276, oral, QD + Cetuximab, Cetuximab:
其他名称：
Phase II Cohort A：GFH276, oral +FOLFIRI/mFOLFOX6±bev, IV, Q4W, d1,d15
其他名称：
Phase Ib - Dose Escalation Cohort 3：GFH276 in combination with cetuximab， Cetuximab:
其他名称：
|
|
有源比较器：Phase II:Cohort C
FOLFIRI/mFOLFOX6+bev, IV |
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 and severity of AEs and SAEs
大体时间：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
大体时间：First 28 days
|
The incidence of DLT events |
First 28 days
|
|
Phase II: Objective response rate （ORR）
大体时间：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
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
ORR:
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
|
合作者和调查者
调查人员
- 首席研究员：ruihua xu, MD、Sun Yat-Sen University Cancer Center
研究记录日期
研究主要日期
学习开始 (估计的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- GFH276X1202
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)？
药物和器械信息、研究文件
研究美国 FDA 监管的药品
研究美国 FDA 监管的设备产品
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