A Multicenter, Open-Label, Phase Ib/II Clinical Study to Explore the Efficacy, Pharmacokinetics and Safety/Tolerability of GFH375 in Combination With Cetuximab or Chemotherapy in Participants With Advanced Solid Tumors Harboring KRAS G12D Mutation
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 126
- 试验地点
- 4
- 主要终点
- Phase Ib: Incidence of Dose-Limiting Toxicity (DLT) Events
研究概览
简要总结
This is a Phase Ib/II clinical study aimed at exploring the safety and efficacy of Regimen A (GFH375 in combination with Cetuximab) and Regimen B (GFH375 in combination with AG) in participants with solid tumors.Phase Ib: To evaluate the safety/tolerability and pharmacokinetic (PK) characteristics of GFH375 in combination with cetuximab or AG in participants with solid tumors, and to explore the efficacy of the combination therapy. Phase II: To evaluate the efficacy, safety/tolerability and PK characteristics of the combination therapy, and to explore the correlation between bio-marker and clinical efficacy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Voluntarily participate in the study and sign the informed consent form.
- •Participants receiving Regimen A must be ≥ 18 years old when signing the informed consent form, and participants receiving Arm B must be 18 - 75 years old.
- •Histologically or cytologically confirmed locally advanced unresectable or metastatic solid tumors, with KRAS G12D mutation.
- •Failed standard systemic treatment, or intolerant to standard treatment, or unsuitable for standard treatment, or no standard treatment available.
- •At least one measurable lesions according to RECIST v1.1
- •Participants receiving Regimen A must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 - 2; participants receiving Regimen B must have an ECOG PS score of 0 -
- •Have sufficient organ function.
排除标准
- •Symptomatic brain metastasis, leptomeningeal metastasis, spinal cord compression, or primary brain tumor.
- •Presence of known coexisting other cancer driver genes.
- •Previous or active history of clinically significant cardiovascular dysfunction.
- •Presence of active infection.
- •History of central nervous system (CNS) diseases.
- •Presence of clinically significant interstitial lung disease, radiation pneumonitis, or immune-related pneumonitis requiring treatment.
- •Newly diagnosed deep vein thrombosis or pulmonary embolism within 3 months before the first administration of the study treatment.
- •Presence of uncontrolled or symptomatic pleural effusion, ascites, or pericardial effusion.
- •Having received major surgery within 28 days before the start of the study treatment; having experienced major trauma within 14 days before the start of the study treatment; or planning to undergo major surgery during the study period.
- •Having received radiotherapy within 4 weeks before the start of the study treatment, or having received palliative radiotherapy for bone metastatic lesions within 2 weeks before the start of the study treatment.
结局指标
主要结局
Phase Ib: Incidence of Dose-Limiting Toxicity (DLT) Events
时间窗: up to 28 days
Phase Ib: Incidence and Severity of Adverse Events (AE) and Serious Adverse Events (SAE)
时间窗: From the first dose until 30 days after the last dose, assessed up to 24 months
Phase II: Objective Response Rate (ORR) Evaluated by RECIST 1.1
时间窗: 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
次要结局
- Plasma concentrations of GFH375(up to 6 months)
- Phase II: Incidence and Severity of AE and SAE(From the first dose until 30 days after the last dose, assessed up to 24 months)
- PFS(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(From the first dose until date of death from any cause, assessed up to 24 months)
- 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)
- TTR(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(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)