Glecirasib Combined With Ivonescimab for First-line Treatment of KRAS G12C-mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer: A Prospective, Multi-center, Phase I/II Clinical Study
概览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 42
- 主要终点
- Phase I: Maximum Tolerated Dose (MTD)
概览
简要总结
This study evaluates the safety, tolerability, maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), and recommended phase II dose (RP2D) of Glecirasib in combination with Ivonescimab in patients with previously untreated, KRAS G12C-mutated, locally advanced or metastatic non-small cell lung cancer (NSCLC) with PD-L1 TPS ≥1%. The study includes a Phase I 3+3 dose-escalation stage followed by a Phase II Simon two-stage design to assess preliminary antitumor efficacy.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed written informed consent.
- •Age ≥18 years.
- •Newly diagnosed, unresectable, locally advanced (ineligible for curative concurrent - chemoradiotherapy) or metastatic NSCLC per AJCC 9th edition.
- •KRAS G12C mutation confirmed by validated testing.
- •PD-L1 TPS ≥1%.
- •≥1 measurable lesion per RECIST v1.
- •No prior systemic therapy for advanced/metastatic NSCLC; prior adjuvant therapy allowed if completed \>6 months before dosing and toxicities recovered to ≤Grade
- •ECOG PS 0-
- •Life expectancy \>3 months
- •Adequate organ function (hematologic, hepatic, renal, coagulation per protocol thresholds)
排除标准
- •History of other malignancies (exceptions: cured basal cell carcinoma, cervical carcinoma in situ)
- •Predominant squamous NSCLC, small cell carcinoma, or neuroendocrine carcinoma.
- •Other actionable drivers (EGFR, ALK, ROS1, RET, BRAF, NTRK, MET, etc.).
- •Known hypersensitivity to study drugs.
- •Prior PD-1/PD-L1 inhibitors or KRAS inhibitors.
- •Active autoimmune disease or autoimmune disease history requiring systemic therapy.
- •Systemic immunosuppressive therapy within 14 days prior to first dose.
- •Symptomatic ascites/pleural effusion needing recurrent drainage.
- •Significant cardiovascular disease (NYHA ≥2, MI within 1 year, uncontrolled arrhythmias).
- •Active infection, unexplained fever \>38.5°C.
研究组 & 干预措施
Glecirasib Combined With Ivonescimab
干预措施: Ivonescimab (Drug)
Glecirasib Combined With Ivonescimab
干预措施: Glecirasib (Drug)
结局指标
主要结局
Phase I: Maximum Tolerated Dose (MTD)
时间窗: 21 days after the first dose.
The MTD is determined using a standard 3+3 dose-escalation design. It is defined as the dose level prior to the dose at which ≥2 out of 3-6 patients experience a Dose-Limiting Toxicity (DLT) within the first 21 days of treatment
Phase I: Incidence of Dose-Limiting Toxicities (DLTs)
时间窗: 21 days after the first dose.
Evaluation of toxicities related to the study drugs, including hematologic and non-hematologic toxicities as defined in the protocol.
Phase I: Recommended Phase 2 Dose (RP2D)
时间窗: 21 days after the first dose.
The RP2D of Glecirasib in combination with Ivonescimab will be selected based on the comprehensive evaluation of the MTD, DLT occurrences, and overall safety data observed during the Phase I escalation phase. This dose will then be utilized in the Phase II Simon's two-stage expansion to further evaluate efficacy and safety.
Phase II: Objective Response Rate (ORR)
时间窗: Assessed up to 24 months
The proportion of patients who achieve a Complete Response (CR) or Partial Response (PR) based on RECIST v1.1.
次要结局
- Disease Control Rate (DCR)(Up to 24 months)
- Progression-Free Survival (PFS)(Up to 24 months)
- Duration of Response (DOR)(Up to 24 months)
- Overall Survival (OS)(Up to 24 months)
- Incidence of Adverse Events (AEs)(From first dose enrollment through 28 days after the last dose.)
研究者
Zhijie Wang
Professor
Cancer Institute and Hospital, Chinese Academy of Medical Sciences