A Phase 1, Open Label, Dose Escalation of HBI-2438 in Patients With Advanced Malignant Solid Tumors Harboring KRAS G12C Mutation
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 44
- 试验地点
- 9
- 主要终点
- To determine the maximum tolerated dose (MTD)
研究概览
简要总结
A Phase 1 dose escalation study in patients with advanced solid tumors harboring KRAS G12C mutation to determine the maximum tolerated dose and recommended Phase II dose of HBI-2438 and characterize its pharmacokinetic profile.
详细描述
A Phase 1, Open-Label, Dose Escalation of HBI-2438 in Patients with Advanced Malignant Solid Tumors Harboring KRAS G12C Mutation. The primary and secondary objectives are:
- To determine the MTD and recommended Phase 2 dose (RP2D) of HBI-2438 as an oral monotherapy for advanced solid tumors harboring KRAS G12C mutation.
- To characterize the PK of HBI-2438 in subjects with advanced malignant solid tumors harboring KRAS G12C mutation.
HBI-2438 is an orally administered KRAS G12C Inhibitor and will be dosed once daily throughout the escalation and expansion phase. Up to 44 subjects will be enrolled sequentially into the 3+3 dose escalation and monitored throughout the study for safety and tolerability. The dose escalation phase will consist of 6 cohorts, with doses ranging from 150 to 1200mg. Once the MTD of RP2D is established, an additional 6-8 subjects with brain metastases will be enrolled into the expansion phase at that dose level.
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
- •Key Inclusion Criteria:
- •Male or female at least 18 years of age at the time of signing the ICF prior to initiation of any study specific activities/procedures
- •Advanced malignant solid tumors with KRAS G12C mutation- as determined by genetic testing
- •Must have failed or refused standard of care therapy, are not eligible for standard of care therapy, or cannot benefit from standard of care therapy, in the opinion of the Investigator
- •At least 1 measurable target lesion that meets the definition of RECIST v1.1
- •ECOG Performance Status of 0 or 1
- •Demonstrate adequate organ function
- •Expected survival time > 3 months in the opinion of the investigator
- •Must be able to swallow oral medications and must not have gastrointestinal abnormalities that significantly affect drug absorption
排除标准
- •Key Exclusion Criteria:
- •History of another concurrent malignancy within 3 years prior to study entry, unless the malignancy was treated with curative intent and the likelihood of relapse is <5% in 2 years Note: Subjects with a history of squamous or basal cell carcinoma of the skin or carcinoma in the situ of the cervix may be enrolled
- •Untreated or symptomatic central nervous system (CNS) metastases Note: Subjects with asymptomatic treated CNS metastases are eligible provided they have been clinically stable and not requiring steroids for at least 4 weeks
- •Clinically significant cardiovascular disease, including stroke or myocardial infarction within 6 months prior to first dose of HBI-2438; or the presence of unstable angina or congestive heart failure of New York Heart Association Grade 2 or higher
- •Any unresolved Grade 2 or greater toxicity from previous anti-cancer therapy, except alopecia, within 4 weeks of first study treatment administration
- •Active autoimmune diseases or history of autoimmune diseases that may relapse
- •Pregnant or nursing
- •Prior treatment with any KRAS G12C inhibitors
- •Any condition that required systemic treatment with either corticosteroids (>10 mg daily of prednisone or equivalent) or other immunosuppressive medication ≤14 days before the first study treatment administration
- •Treatment with other investigational drugs/devices within 4 weeks prior to first study treatment administration
研究组 & 干预措施
Dose Escalation and Expansion
HBI-2438 will be given orally in ascending doses (escalation cohort), until the maximum tolerated dose or recommended Phase 2 dose is reached. Up to 6-8 patients will then be enrolled in the expansion cohort at the recommended dose.
干预措施: HBI-2438 (Drug)
结局指标
主要结局
To determine the maximum tolerated dose (MTD)
时间窗: Up to 36 months
Safety endpoints: Incidence of dose-limiting toxicities (DLTs)
adverse events (AEs), and serious adverse events (SAEs) overall
时间窗: Up to 36 months
Safety endpoints: adverse events (AEs), and serious adverse events (SAEs) overall
次要结局
- minimum plasma concentration (Cmin)(Cycle 1 (21 days))
- maximum plasma concentration (Cmax)(Cycle 1 (21 days))
- Area Under the Curve (AUC)(Cycle 1 (21 days))
- Pharmacokinetic variables including clearance(Cycle 1 (21 days))
- Pharmacokinetic variables including serum half-life(Cycle 1 (21 days))
- Pharmacokinetic variables including volume of distribution(Cycle 1 (21 days))