A Phase 1 Study of a Selective AKT1 E17K Allosteric Inhibitor, ATV-1601, in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 134
- 试验地点
- 9
- 主要终点
- Expansion: Trough Concentrations
研究概览
简要总结
This is a Phase 1, open-label study to evaluate the safety and tolerability of ATV-1601 administered orally in adults with AKT1 E17K-mutant, advanced solid tumors and also in HR+/HER2- advanced and metastatic breast cancer, with or without fulvestrant.
详细描述
This is a first-in-human, open-label, multicenter, Phase 1a/1b dose escalation dose finding, and dose expansion study to evaluate safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of ATV-1601 as monotherapy in participants with advanced or metastatic solid tumors with the AKT1 E17K mutation, and in combination with fulvestrant in participants with breast cancer that has the AKT1 E17K mutation. This study has a dose escalation and expansion phase with ATV-1601, and an escalation and expansion phase in combination with Fulvestrant.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Histologically or cytologically confirmed metastatic or advanced-stage solid malignant tumor or HR+/HER2- breast cancer.
- •Have progressed on, were intolerant to, or experienced disease recurrence after standard therapy and have no available effective or tolerable treatment options to derive clinically meaningful benefit.
- •Tumor must have documented specific mutation profile as outlined below based on local laboratory testing.
- •Participants with solid tumors or HR+/HER2- breast cancer with AKT1 E17K mutations.
- •Measurable disease according to RECIST v1.1 criteria.
- •Formalin-fixed paraffin-embedded tumor specimen available for submission.
- •Eastern Cooperative Oncology Group performance status of 0 or 1.
排除标准
- •Previously documented activating mutations in KRAS, NRAS, HRAS, or BRAF.
- •Inadequate bone marrow reserve or organ function.
- •Clinically significant abnormalities of glucose metabolism.
- •Participants who are symptomatic or have uncontrolled brain metastases.
- •Requires treatment with certain medications.
- •Participants must meet other inclusion/exclusion criteria.
研究组 & 干预措施
Experimental/Part 1b: ATV-1601 + Fulvestrant
ATV-1601 + Fulvestrant
干预措施: ATV-1601 + Fulvestrant (Combination Product)
Experimental/Part 1a: ATV-1601
ATV-1601
干预措施: ATV-1601 (Drug)
结局指标
主要结局
Expansion: Trough Concentrations
时间窗: Approximately 48 months
Drug concentration in Blood
Expansion: Half-life
时间窗: Approximately 48 months
Drug concentration in Blood
Expansion: AUC extrapolated to infinity
时间窗: Approximately 48 months
Drug concentration in Blood
Expansion: Maximum and minimum plasma concentration
时间窗: Approximately 48 months.
Drug concentration in Blood.
Expansion: Time to C Max
时间窗: Approximately 48 months
Drug concentration in Blood
Expansion: Area under the concentration-time curve
时间窗: Approximately 48 months
Drug concentration in Blood
Expansion: AUC at end of dosing interval
时间窗: Approximately 48 months
Drug concentration in Blood
Expansion: Maximum and minimum plasma concentration
时间窗: Approximately 48 months.
Drug concentration in Blood.
Expansion: Trough Concentrations
时间窗: Approximately 48 months
Drug concentration in Blood
Expansion: Time to C Max
时间窗: Approximately 48 months
Drug concentration in Blood
Expansion: Half-life
时间窗: Approximately 48 months
Drug concentration in Blood
Expansion: Area under the concentration-time curve
时间窗: Approximately 48 months
Drug concentration in Blood
Expansion: AUC at end of dosing interval
时间窗: Approximately 48 months
Drug concentration in Blood
Escalation & Expansion: Safety and Tolerability of monotherapy.
时间窗: Approximately 48 months.
Number of participants with Treatment Emergent Adverse Events (TEAEs). Safety will be assessed by monitoring adverse events, laboratory tests and ECG results.
Escalation: Maximum tolerated dose and/or recommended phase 2 dose of ATV-1601 in monotherapy.
时间窗: Approximately 48 months.
Number of patients with dose-limiting toxicities.
Escalation: Maximum tolerated dose and/or recommended phase 2 dose of ATV-1601 combination with fulvestrant.
时间窗: Approximately 48 months.
Number of patients with dose-limiting toxicities.
Expansion: AUC extrapolated to infinity
时间窗: Approximately 48 months
Drug concentration in Blood
次要结局
- Escalation: Trough Concentrations(Approximately 48 months)
- Escalation & Expansion: Objective response rate(Approximately 48 months)
- Escalation: Maximum and minimum plasma concentration(Approximately 48 months.)
- Escalation: Time to C max(Approximately 48 months)
- Escalation: Area under the concentration-time curve(Approximately 48 months)
- Escalation: AUC at end of dosing interval(Approximately 48 months)
- Escalation: AUC extrapolated to infinity(Approximately 48 months)
- Escalation: Half-life(Approximately 48 months)
- Escalation & Expansion: Duration of Response(Approximately 48 months)
- Escalation & Expansion: Clinical Benefit Rate(Approximately 48 months)
- Expansion: Progression Free Survival(Approximately 48 months)