A Phase 1, Open-Label, Dose Escalation of HBI-2376 in Patients With Advanced Malignant Solid Tumors Harboring KRAS or EGFR Mutations
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 42
- 试验地点
- 11
- 主要终点
- To determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D), of HBI-2376 as an oral monotherapy for advanced solid tumors harboring KRAS or EGFR mutations.
研究概览
简要总结
A Phase 1 dose escalation study in patients with advanced solid tumors harboring KRAS or EGFR mutations to determine the maximum tolerated dose and recommended Phase II dose of HBI-2376 and characterize its pharmacokinetic profile.
详细描述
A Phase 1, Open-Label, Dose Escalation of HBI-2376 in Patients with Advanced Malignant Solid Tumors Harboring KRAS or EGFR Mutations. The primary and secondary objectives are:
- To determine the MTD and recommended Phase 2 dose (RP2D), of HBI-2376 as an oral monotherapy for advanced solid tumors harboring KRAS or EGFR mutations
- To characterize the PK of HBI-2376 in subjects with advanced malignant solid tumors harboring KRAS or EGFR mutations
HBI-2376 is a SHP2 Inhibitor and will be dosed once daily throughout the escalation and expansion phase. Up to 42 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 6 to 40mg. Once the MTD of RP2D is established, additional 6 subjects 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
- •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 or EGFR mutations diagnosed by histology or cytology
- •Relapsed or refractory to, or intolerant of, or refuse approved or standard of care established therapy known to provide clinical benefit for disease
- •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
- •Must be able to swallow oral medications and must not have gastrointestinal abnormalities that significantly affect drug absorption
排除标准
- •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
- •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 SHP2 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-2376 will be given orally in ascending doses (escalation cohort), until the maximum tolerated dose or recommended Phase 2 dose is reached. Up to 6 patients will then be enrolled in the expansion cohort at the recommended dose.
干预措施: HBI-2376 (Drug)
结局指标
主要结局
To determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D), of HBI-2376 as an oral monotherapy for advanced solid tumors harboring KRAS or EGFR mutations.
时间窗: Up to 36 months
Safety endpoints: Incidence of dose-limiting toxicities (DLTs), adverse events (AEs), and serious adverse events (SAEs) overall, by severity, by relationship to HBI-2376, and those that led to discontinuation of HBI-2376
次要结局
- Pharmacokinetic variables including Area Under the Curve (AUC)(Cycle 1 (28 days))
- Pharmacokinetic variables including clearance(Cycle 1 (28 days))
- Pharmacokinetic variables including serum half-life(Cycle 1 (28 days))
- Pharmacokinetic variables including volume of distribution(Cycle 1 (28 days))
- Pharmacokinetic variables including maximum plasma concentration (Cmax)(Cycle 1 (28 days))
- Pharmacokinetic variables including minimum plasma concentration (Cmin)(Cycle 1 (28 days))