A Phase 1b Trial of ARV-471 in Combination With Everolimus in Patients With ER+, HER2- Advanced or Metastatic Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Incidence of dose limiting toxicities of ARV-471 in combination with everolimus
研究概览
简要总结
A phase 1b study to assess the combination of ARV-471 and everolimus in participants with advanced or metastatic ER+/HER2- breast cancer.
详细描述
This is a Phase 1b study to assess the safety and tolerability of ARV-471 in combination with everolimus in participants with estrogen receptor positive/human epidermal growth factor receptor 2 negative (ER+/HER2-) advanced or metastatic breast cancer, who have received a prior CDK4/6 inhibitor and endocrine therapy in the advanced/metastatic setting.
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
- •Histologically or cytologically confirmed ER+ and HER2-advanced breast cancer (metastatic, recurrent, or unresectable)
- •Women must be postmenopausal, or pre-/peri-menopausal women must be on ovarian suppression
- •Measurable disease or non-measurable (evaluable) disease per RECIST v1.1
- •Received a minimum of 1 and up to 3 lines of anti-cancer therapy in the advanced/metastatic setting: must have received and progressed on (or were intolerant to) a CDK 4/6 inhibitor, either alone or in combination; must have received at least one endocrine therapy, either alone or in combination; may have received up to one line of chemotherapy
- •Must be willing to use dexamethasone mouthwash for the prevention of everolimus-induced stomatitis
- •ECOG performance status of 0 or 1
排除标准
- •Untreated brain metastases or brain metastases requiring steroids above physiologic replacement doses
- •Prior treatment with ARV-471
- •Prior treatment targeting mTOR (e.g. everolimus)
- •Prior anticancer or investigational drug treatment within 28 days (fulvestrant) or 14 days (tamoxifen or aromatase inhibitor, or CDK 4/6 inhibitor) before the first dose of study drug
- •Prior anticancer or investigational anticancer drug therapy within 28 days or 5 half-lives (whichever is shorter) before the first dose of study drug, except as mentioned above
- •Any of the following in the previous 12 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, symptomatic pulmonary embolism, or other clinically significant episode of thromboembolism
- •Any of the following in the previous 6 months: congenital long QT syndrome, Torsade de Pointes, sustained ventricular tachyarrhythmia and ventricular fibrillation, left anterior hemiblock, ongoing cardiac arrythmias/dysrhythmias, atrial fibrillation
- •Hypertension that cannot be controlled by medication (>150/90 mmHg despite optimal medical therapy)
- •Active, uncontrolled bacterial, fungal, or viral infection, including hepatitis B virus, hepatitis C virus, known human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS)-related illness
- •Known history of drug-induced pneumonitis or other significant symptomatic deterioration of lung function
- •Live vaccines within 14 days before the first dose of study drug
- •Major surgery (as defined by the Investigator) within 4 weeks of first dose of study drug
- •Radiation therapy within 4 weeks of first dose of study drug or prior irradiation to more than 25% of the bone marrow
研究组 & 干预措施
ARV-471 and Everolimus
ARV-471 oral tablets in combination with everolimus administered daily in 28 day cycles
干预措施: ARV-471 in combination with Everolimus (Drug)
结局指标
主要结局
Incidence of dose limiting toxicities of ARV-471 in combination with everolimus
时间窗: 35 Days
Dose limiting toxicities in the first 35 days of the study combination treatment characterized by type, frequency, severity (as graded by NCI CTCAE v5.0), timing, seriousness, and relationship to study drug
Recommended Phase 2 Dose (RP2D) for ARV-471 in combination with everolimus
时间窗: 35 Days
Number of participants with adverse events as a measure of safety and tolerability of ARV-471 in combination with everolimus
时间窗: 28 calendar days after participant discontinues study treatment
Adverse events as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study drug combination
Incidence of laboratory abnormalities as a measure of safety and tolerability of ARV-471 in combination with everolimus
时间窗: 28 calendar days after participant discontinues study treatment
Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE v5.0), and timing
次要结局
- Duration of response (DOR) in participants(Up to approximately 1 year)
- Maximum plasma concentrations (Cmax) of ARV-471 and everolimus(At predefined intervals throughout the treatment period, up to approximately 4 weeks after last dose of investigational products)
- Overall response rate (ORR) in participants(Up to approximately 1 year)
- Clinical benefit rate (CBR) in participants.(Up to approximately 1 year)
- Time to maximum plasma concentrations (Tmax) of ARV-471 and everolimus(At predefined intervals throughout the treatment period, up to approximately 4 weeks after last dose of investigational products)
- Area under the concentration-time curve over 24 hours at steady state (AUC(0-24)) of ARV-471 and everolimus(At predefined intervals throughout the treatment period, up to approximately 4 weeks after last dose of investigational products)