A Phase I, Open-Label Study of ABSK211 to Assess Safety, Tolerability, Efficacy and Pharmacokinetics in Participants With Advanced Solid Tumors With KRAS Alteration
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 247
- 试验地点
- 2
- 主要终点
- Incidence of DLTs
研究概览
简要总结
This is a first-in-human (FIH), multicenter, open-label, phase I study of ABSK211 in participants with advanced solid tumors to evaluate safety, tolerability, PK and optimize the dosage.
详细描述
The study will start with a dose escalation of oral ABSK211 in participants with advanced solid tumors with KRAS alteration to evaluate safety, tolerability, and PK. The expansion part will evaluate the safety and efficacy of oral ABSK211 at the recommended doses for expansion (RDEs) in selected tumor types harboring KRAS alteration and further optimize the dosage.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 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
- •Participants should understand, sign, and date the written informed consent form prior to screening.
- •Male or female age 18 years or older
- •Participants with histologically confirmed locally-advanced or metastatic solid tumors harboring KRAS alteration
- •ECOG performance status 0 or 1
- •Life expectancy ≥ 3 months
- •Adequate organ function and bone marrow function
- •For participants participating exploration of food effect:
- •be able to eat a standardized high-fat, high caloric meal within 30 minutes. 2) be able to fast for 10 hours.
排除标准
- •Known allergy or hypersensitivity to any component of the investigational product
- •Participants who were previously treated with any inhibitors targeting specific KRAS alleles, pan-KRAS inhibitors, pan- or multi-RAS inhibitors, or any other treatments directly targeting RAS.
- •Has a known additional malignancy that is progressing or has required active treatment
- •Has swallowing dysfunction or malabsorption syndrome
- •Previous anti-tumor therapy, including chemotherapy ,endocrine therapy, molecular targeted therapy or other investigational drugs received ≤2 weeks or ≤5-half life ,radiotherapy and antibody therapy received ≤4 weeks prior to initiation of study treatment.
- •Major surgery within 4 weeks of the first dose of investigational product or with any unhealed surgical wounds, infection or dehiscence.
- •Prior toxicities from chemotherapy, radiotherapy, and other anti-cancer therapies, including immunotherapy, that have not regressed to Grade ≤1 severity;
- •Participants use proton pump inhibitors for at least 7 days prior to the first dose of ABSK211 and during treatment with ABSK
- •P-gp inhibitor, moderate and strong CYP3A inhibitors to 7 days or 5 half-lives and for strong CYP3A inducers to 2 weeks or 5 half-lives ;
- •Active central nervous system (CNS) metastases;
- •History of interstitial lung disease (ILD) requiring systemic steroid treatment;
- •Heart disease or medical history ;
- •NSCLC cohorts: Participant previously identified as having a driver mutation and have not received any targeted therapy;
- •Known acquired immunodeficiency syndrome (AIDS)-related illness, or positive test for HIV 1/2 antibody;
- •Exclusion of hepatitis infection;
- •Participants with refractory/uncontrolled ascites or pleural effusion;
- •Pregnant or nursing (lactating) women;
- •Partners of non-surgically sterilized male participants or female participants of childbearing potential who refuse to use effective methods of birth control during the study and for up to 6 months after the last dose of investigational product;
- •Sexually active males who refuse to use a condom during medication period and until 3 months after stopping investigational product;
- •Vaccination with a live, attenuated vaccine within 4 weeks prior to the first dose of study treatment except for administration of inactivate vaccines ;
- •Any other clinically significant comorbidities, such as uncontrolled pulmonary disease, active infection, or any other condition;
研究组 & 干预措施
ABSK211
During the escalation part ,all participants will firstly receive a single dose of ABSK211 as a run-in period to access the safety and PK of ABSK211. Then, participants will continuously receive ABSK211 once daily (QD), with each treatment cycle of 21 days； In the expansion part，participants will orally receive ABSK211 at the recommended dose for expansion (RDE).
干预措施: ABSK211 (Drug)
结局指标
主要结局
Incidence of DLTs
时间窗: from Run-in to Day21
dose-limiting toxicities
AEs
时间窗: The date of signing the informed consent form until 30 days (including Day 30) after the last administration of investigational product
Adverse events
SAEs
时间窗: The date of signing the informed consent form until 30 days (including Day 30) after the last administration of investigational product
Serious adverse events (SAEs)
次要结局
- Tmax(from pre-dose to up to 72 hours post-dose)
- AUC(from pre-dose to up to 72 hours post-dose)
- t1/2(from pre-dose to up to 72 hours post-dose)
- Cmax(from pre-dose to up to 72 hours post-dose)
- CL/F(from pre-dose to up to 72 hours post-dose)
- ORR(throughout study completion, assessed up to 24 months)
- DOR(throughout study completion, assessed up to 24 months)
- DCR(throughout study completion, assessed up to 24 months)
- PFS(throughout study completion, assessed up to 24 months)
- OS(throughout study completion, assessed up to 24 months)
- Vz/F(from pre-dose to up to 72 hours post-dose)
- AR(from pre-dose to up to 72 hours post-dose)
- BPR(from pre-dose to up to 72 hours post-dose)