A Phase 1/2, Open Label, Dose Escalation, and Cohort Expansion Clinical Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of ARV-471 Alone and in Combination With Palbociclib (IBRANCE®) in Patients With Estrogen Receptor Positive/Human Epidermal Growth Factor Receptor 2 Negative (ER+/HER2-) Locally Advanced or Metastatic Breast Cancer, Who Have Received Prior Hormonal Therapy and Chemotherapy in the Locally Advanced/Metastatic Setting
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 217
- 试验地点
- 16
- 主要终点
- Part A: Incidence of Dose Limiting Toxicities of ARV-471
研究概览
简要总结
This is a Phase 1/2 dose escalation and cohort expansion study and will assess the safety, tolerability and anti-tumor activity of ARV-471 alone and in combination with palbociclib (IBRANCE®) in patients with estrogen receptor positive/human epidermal growth factor receptor 2 negative (ER+/HER2-) locally advanced or metastatic breast cancer, who have received prior hormonal therapy and chemotherapy in the locally advanced/metastatic setting.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Part A, Part B, and Part C:
- •Patients at least 18 years of age at the time of signing the informed consent.
- •Patients must have histologically or cytologically confirmed ER+ and HER2- advanced breast cancer for which standard curative therapy is no longer effective or does not exist.
- •Patients must have measurable or non-measurable disease by RECIST criteria (version1.1), with radiologic tumor assessments performed within 28 days of the first dose of therapy.
- •Patients must be willing to undergo a core biopsy of accessible tumor within 4 weeks prior to the initiation of study treatment and a follow-up biopsy on treatment for ER immunohistochemistry (IHC) testing and pharmacodynamics (PD) studies. (Patients without accessible tumor tissue may be eligible after discussion with the Medical Monitor.)
- •Women must be postmenopausal due to surgical or natural menopause.
- •- Patients must have received at least 2 prior endocrine regimens in any setting (neoadjuvant, adjuvant or advanced/metastatic) a CDK4/6 inhibitor and up to 3 prior regimens of cytotoxic chemotherapy in the locally advanced or metastatic setting.
- •Patients must have received at least 1 prior endocrine regimen for a minimum of 6 months in the locally advanced or metastatic setting; if more than 1 prior endocrine regimen has been administered, only one of the regimens must have been administered for a minimum of 6 months in the locally advanced or metastatic setting
- •Patients must have received a CDK4/6 inhibitor
- •Patients must have received up to 1 prior regimen of cytotoxic chemotherapy in the locally advanced or metastatic setting
- •Women must be postmenopausal due to surgical or natural menopause.
- •Patients must have received at least one prior endocrine regimen.
- •Patients must have received no more than two prior chemotherapy regimens for advanced disease.
- •Women must be postmenopausal due to surgical or natural menopause.
排除标准
- •Part A, Part B, and Part C:
- •Patients with known symptomatic brain metastases requiring steroids (above physiologic replacement doses). Patients with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to first dose of study drug, have discontinued high-dose corticosteroid treatment for these metastases for at least 4 weeks and are neurologically stable as judged by the Investigator.
- •Receipt of prior anti-cancer or other investigational therapy within 14 days prior to the first administration of study drug.
- •Radiation therapy within 4 weeks of first dose of study drug or prior irradiation to >25% of the bone marrow. Palliative radiation for the alleviation of pain due to bone metastasis will be allowed during the study.
研究组 & 干预措施
ARV-471 and palbociclib (IBRANCE®)
Part C: Daily oral dosages of ARV-471 for 28 days in combination with palbociclib (IBRANCE®) for 21 days.
干预措施: ARV-471 in combination with palbociclib (IBRANCE®) (Drug)
ARV-471
Parts A and B: ARV-471 administered once daily (QD) or twice daily (BID) for 28 day cycles.
干预措施: ARV-471 (Drug)
结局指标
主要结局
Part A: Incidence of Dose Limiting Toxicities of ARV-471
时间窗: 28 Days
First Cycle Dose limiting toxicities characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study drug
Part A: Number of Patients with Adverse Events as a measure of safety and tolerability of ARV-471
时间窗: First study drug dose through a minimum of 30 calendar Days After Last study drug administration
Adverse events as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study drug.
Part A: Incidence of laboratory abnormalities as a measure of safety and tolerability of ARV-471
时间窗: First study drug dose through a minimum of 30 calendar Days After Last study drug administration
Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing.
Part B: Assessment of anti-tumor activity of ARV-471
时间窗: through study completion, up to approximately 2 years
Clinical benefit response rate based on the summation of CRs, PRs and stable disease of 24 weeks duration or longer
Part C: Incidence of Dose Limiting Toxicities of combination ARV-471 + palbociclib
时间窗: 28 Days
First cycle dose-limiting toxicities and determination of a maximum tolerated dose (MTD) if applicable among the doses evaluated
Part C: Number of Patients with Adverse Events as a measure of safety and tolerability of combination ARV-471 + palbociclib
时间窗: First study drug dose through a minimum of 30 calendar Days After Last study drug administration
Adverse events as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study drug combination
Part C: Incidence of laboratory abnormalities as a measure of safety and tolerability of combination ARV-471 + palbociclib
时间窗: First study drug dose through a minimum of 30 calendar Days After Last study drug administration
Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing
次要结局
- Part A: Assessment of pharmacokinetic parameter maximum concentration (Cmax).(At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of ARV-471)
- Part A: Assessment of pharmacokinetic parameter minimum concentration (Cmin).(At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of ARV-471)
- Part A: Assessment of pharmacokinetic parameter time to maximum concentration (Tmax).(At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of ARV-471)
- Part B: Evaluation of Plasma Concentrations of ARV-471(At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of investigational products])
- Part C:Assessment of pharmacokinetic parameter area under the concentration-time curve (AUC)(At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of investigational products)
- Part C: Assessment of pharmacokinetic parameter maximum concentration (Cmax).(At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of investigational products)
- Part C: Assessment of pharmacokinetic parameter minimum concentration (Cmin).(At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of investigational products)
- Part C: Assessment of pharmacokinetic parameter time to maximum concentration (Tmax)(At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of investigational products)
- Part A: Assessment of anti-tumor activity of ARV-471(through study completion, up to approximately 2 years)
- Part B: Assessment of anti-tumor activity of ARV-471(through study completion, up to approximately 2 years)
- Part B: Evaluation of Safety and Tolerability(First study drug dose through a minimum of 30 calendar Days After Last study drug administration)
- Part C: Assessment of anti-tumor activity of ARV-471 in combination with palbociclib(through study completion, up to approximately 2 years)
- Part A: Assessment of pharmacokinetic (PK) parameter area under the concentration-time curve (AUC).(At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of ARV-471)