A Phase Ib/II Clinical Study Evaluating the Safety, Tolerability, Pharmacokinetics and Efficacy of GH21 Capsule Combined With D-1553 Tablets in Patients With Locally Advanced or Metastatic Solid Tumors Harboring KRAS G12C Mutation
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 126
- 主要终点
- Dose-limiting Toxicities Incidence Count Among Study
研究概览
简要总结
This s a multi-center, open-label phase Ib/II study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of GH21 combined with D-1553 in patients with advanced or metastatic solid tumors harboring KRAS G12C mutation.
详细描述
This study includes 2 parts: dose escalation(Phase Ib) and dose expansion (Phase II). The objective of the dose escalation part is to evaluate the safety, tolerability and pharmacokinetics of GH21 in combination with D-1553 in patients with advanced solid tumors harboring KRAS G12C mutation and to determine the RP2D for the combination therapy. In the dose expansion part, preliminary efficacy and safety of the combination therapy at the RP2D will be further explored in patients with specific cancer harboring KRAS G12C mutation.
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
- •The patient or his legal representative is able to understand and voluntarily sign a written informed consent (before commencing this study and any research procedure);
- •Age ≥18 years old, male or female;
- •KRAS G12C mutant advanced solid tumor;
- •ECOG Performance Status of 0 or 1
- •At least one measurable lesion as defined by RECIST 1.1
排除标准
- •acute myocardial infarction, unstable angina pectoris, coronary artery bypass grafting, cerebrovascular accident, or transient ischemic attack within 6 months before first administration; Grade III-IV heart failure based on the New York Heart Association Cardiac Function Scale at screening; During screening, echocardiography (ECHO) showed left ventricular ejection fraction (LVEF) ≤50%;
- •Patients who have a history of severe allergy, or have a history of allergy to the experimental drug/any excipient/combination drug, or have a history of allergy to multiple drugs;
- •There is an active infection (≥ grade 2) requiring anti-infective treatment or an unexplained fever exceeding 38 ° C within 28 days before the first dose;
- •Any toxicity from previous antitumor therapy prior to initial administration has not returned to CTCAE 5.0 rating ≤ Class 1 (unless hair loss, grade 2 peripheral neuropathy, and/or other grade ≤2 adverse events that do not pose a safety risk);
- •Pregnant and lactating women;
- •The investigator considers that there are any clinical or laboratory abnormalities or other reasons to be unsuitable for participating in this clinical study.
研究组 & 干预措施
"GH21 + D-1553" Group
GH21 capsules combined with D-1553 tablets were administrated orally
干预措施: GH21 (Drug)
"GH21 + D-1553" Group
GH21 capsules combined with D-1553 tablets were administrated orally
干预措施: D-1553 (Drug)
结局指标
主要结局
Dose-limiting Toxicities Incidence Count Among Study
时间窗: 2 years
Incidence of dose limiting toxicities (DLTs) in the dose escalation phase.
Participants Number of Participants Reporting Adverse Events (AEs) or Serious Adverse Events (SAEs)Objective
时间窗: 2 years
All patients participating in this study will be assessed for incidence and severity of adverse events (AEs) and serious AEs, including changes in laboratory values, vital signs , etc
次要结局
- response rate (ORR) based on RECIST 1.1 criteria(2 years)
- Disease Control Rate (DCR) based on RECIST 1.1 criteria(2 years)
- Progression-free survival (PFS) based on RECIST 1.1 criteria(2 years)
- Overall survival (OS)(2 years)
- Area under the plasma concentration-time curve (AUC)(2 years)
- Duration of response (DOR) based on RECIST 1.1 criteria(2 years)
- Plasma concentration (Cmax)(2 years)
- Time to achieve Cmax (Tmax)(2 years)