A Phase Ib/II, Multicenter, Open-Label Study To Evaluate Safety, Efficacy And Pharmacokinetics Of GFH276 In Combination With Tislelizumab, Pemetrexed And Platinum (Carboplatin Or Cisplatin) As First-Line Therapy In Participants With Locally Advanced Or Metastatic Non-Squamous Non-Small-Cell Lung Cancer Harboring RAS Mutation
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 84
- 主要终点
- Phase Ib:Incidence of Dose-Limiting Toxicity (DLT) Events
研究概览
简要总结
This is an open-label, multicenter Phase Ib/II clinical study evaluating GFH276 in combination with tislelizumab plus pemetrexed/platinum based regimen as first-line therapy in participants with locally advanced or metastatic non-squamous non-small-cell lung cancer (NSCLC) harboring RAS mutation or KRAS amplification.
详细描述
This open-label, multicenter Phase Ib/II study enrolls participants with locally advanced or metastatic non-squamous NSCLC with RAS mutation or KRAS amplification, who have not received prior systemic anti-cancer therapy for advanced disease.
In Phase Ib, dose escalation of GFH276 will be performed in assigned arm to identify the recommended Phase 2 dose (RP2D) based on dose-limiting toxicity (DLT) and the overall safety profile. After RP2D determination, participants will be enrolled in Phase II 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically/cytologically confirmed locally advanced or metastatic non squamous NSCLC (AJCC 8th edition Stage IIIB-IV).
- •Confirmed RAS mutation or KRAS amplification；tumor cell PD L1 test report available
- •No prior systemic anti-tumor therapy for advanced disease
- •At least 1 measurable lesion outside the central nervous system (CNS) per RECIST v1.1
- •ECOG performance status 0 or 1
- •Life expectancy>3 months
- •Willing to provide written informed consent
- •Fertile participants must use effective contraception
- •Adequate organ function
排除标准
- •Other active malignancy within 3 years
- •Symptomatic brain metastases, leptomeningeal disease, spinal cord compression, or primary brain tumor
- •History of active clinically significant cardiovascular dysfunction
- •Known to harbor other targetable driver gene alterations
- •Presence of active infection (HIV, HBV, HCV,)
- •Prior anti-tumor therapy within 28 days or 5 half-lives
- •Diagnosis of unstable thrombotic events requiring therapeutic intervention within 3 months prior to the first dose of study treatment.
- •Hypersensitivity to study drugs, or inability to swallow tablets or comply with study procedures.
- •History of central nervous system (CNS)disease
- •Presence of clinically significant interstitial lung disease, radiation pneumonitis, or immune-related pneumonia that requires treatment.
- •With uncontrollable or symptomatic pleural effusion, ascites, or pericardial effusion.
- •Active autoimmune disease requiring systemic treatment.
研究组 & 干预措施
GFH276 ±Tislelizumab + AP
GFH276 once daily; Tislelizumab 200 mg, IV; AP: Pemetrexed 500 mg/m², IV; Cisplatin/Carboplatin 75 mg/m²/AUC=5, IV, every 3 weeks
干预措施: Cisplatin (Drug)
GFH276 ±Tislelizumab + AP
GFH276 once daily; Tislelizumab 200 mg, IV; AP: Pemetrexed 500 mg/m², IV; Cisplatin/Carboplatin 75 mg/m²/AUC=5, IV, every 3 weeks
干预措施: GFH276 (Drug)
GFH276 ±Tislelizumab + AP
GFH276 once daily; Tislelizumab 200 mg, IV; AP: Pemetrexed 500 mg/m², IV; Cisplatin/Carboplatin 75 mg/m²/AUC=5, IV, every 3 weeks
干预措施: with or without Tislelizumab (Drug)
GFH276 ±Tislelizumab + AP
GFH276 once daily; Tislelizumab 200 mg, IV; AP: Pemetrexed 500 mg/m², IV; Cisplatin/Carboplatin 75 mg/m²/AUC=5, IV, every 3 weeks
干预措施: Pemetrexed (Drug)
GFH276 ±Tislelizumab + AP
GFH276 once daily; Tislelizumab 200 mg, IV; AP: Pemetrexed 500 mg/m², IV; Cisplatin/Carboplatin 75 mg/m²/AUC=5, IV, every 3 weeks
干预措施: Carboplatin (Drug)
结局指标
主要结局
Phase Ib:Incidence of Dose-Limiting Toxicity (DLT) Events
时间窗: First 21 days
The incidence of DLT events
Phase II:Objective Response Rate (ORR)
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 36 months
Assessed by investigators according to RECIST 1.1
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 36 months
The incidence and severity of AEs and SAEs，according to NCI CTCAE，v6.0
次要结局
- 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 36 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 36 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 36 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 36 months)
- OS(From the first dose until date of death from any cause, assessed up to 36 months)
- Phase II: Incidence and Severity of AE and SAE(From the first dose until 30 days after the last dose, assessed up to 36 months)