A Multicenter, Open-label, Phase Ib Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of CYH33 in Combination With Endocrine Therapy With or Without Palbociclib in Patients With PIK3CA Mutant, HR+, HER2- Advanced Breast Cancer
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 228
- 主要终点
- Dose Limiting Toxicities (DLT)
研究概览
简要总结
This is a multicenter, open-label, phase Ib study designed to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of CYH33 administered orally in combination with standard-of-care ET ± CDK4/6 inhibitor therapies for the treatment of locally advanced, recurrent or metastatic hormone-receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) breast cancer. Patients will be enrolled in two stages, including dose exploration phase (Stage 1) and dose expansion phase (Stage 2) of each cohort.
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
- •Provide informed consent voluntarily.
- •Male and female patients ≥ 18 years of age.
- •Patient must have a histologically or cytologically documented locally advanced, recurrent or metastatic breast cancer.
- •In case of women, both premenopausal and postmenopausal patients can be enrolled in the study.
- •Confirmed diagnosis of HR+, HER2- breast cancer.
- •For Stage 1 dose exploration phase, patients with or without PIK3CA mutation may be enrolled; For Stage 2 dose expansion phase, patients with PIK3CA mutations are required.
- •Patient must have evidence of disease radiological progression after previous endocrine therapy, or other systemic therapy.
- •Patient has measurable disease per RECIST v1.
- •Patient must have adequate organ and bone marrow function.
排除标准
- •Previously received any anticancer therapy within 28 days or 5 times of half-lives prior to the first dose of the study treatment.
- •Previously received treatment with any PI3Kα inhibitor, AKT inhibitor, or mTOR inhibitor.
- •Radical radiation therapy within 4 weeks prior to the first dose of the study treatment.
- •Patient with an established diagnosis of diabetes mellitus.
- •Any other concurrent disease with potential risk of insulin resistance or current use of medication with potential risk of insulin resistance.
- •Patient with clinically significant cardiovascular disease.
研究组 & 干预措施
CYH33 + fulvestrant
Participants will receive CYH33 in combination with a standard fixed dose of fulvestrant 500 mg.
干预措施: CYH33 (Drug)
CYH33 + fulvestrant
Participants will receive CYH33 in combination with a standard fixed dose of fulvestrant 500 mg.
干预措施: Fulvestrant (Drug)
CYH33 + fulvestrant + palbociclib
Participants will receive CYH33 in combination with standard fixed dose of fulvestrant (500 mg) and palbociclib (125 mg).
干预措施: CYH33 (Drug)
CYH33 + fulvestrant + palbociclib
Participants will receive CYH33 in combination with standard fixed dose of fulvestrant (500 mg) and palbociclib (125 mg).
干预措施: Fulvestrant (Drug)
CYH33 + fulvestrant + palbociclib
Participants will receive CYH33 in combination with standard fixed dose of fulvestrant (500 mg) and palbociclib (125 mg).
干预措施: Palbociclib (Drug)
CYH33 + letrozole + palbociclib
Participants will receive CYH33 in combination with standard fixed dose of letrozole (2.5 mg) and palbociclib (125 mg)
干预措施: CYH33 (Drug)
CYH33 + letrozole + palbociclib
Participants will receive CYH33 in combination with standard fixed dose of letrozole (2.5 mg) and palbociclib (125 mg)
干预措施: Letrozole (Drug)
CYH33 + letrozole + palbociclib
Participants will receive CYH33 in combination with standard fixed dose of letrozole (2.5 mg) and palbociclib (125 mg)
干预措施: Palbociclib (Drug)
结局指标
主要结局
Dose Limiting Toxicities (DLT)
时间窗: 28 days
Incidence rate of DLT in the first cycle (of 28 days).
次要结局
- Pharmacokinetic measures - C trough(20 months)
- Pharmacokinetic measures - CL/F(20 months)
- Pharmacokinetic measures - Vz/F(20 months)
- Pharmacokinetic measures - AUC(20 months)
- Pharmacokinetic measures - Cmax(20 months)
- Assess downstream effects of PI3K pathway inhibition on blood glucose(20 months)
- Assess downstream effects of PI3K pathway inhibition on C peptide(20 months)
- Preliminary efficacy-PFS(30 months)
- Assess the changes of biomarker-PIK3CA(20 months)
- Safety and tolerability(30 months)
- Preliminary efficacy-ORR(30 months)
- Preliminary efficacy-CBR(30 months)
- Pharmacokinetic measures - Tmax(20 months)
- Assess the changes of biomarker-PTEN(20 months)
- Assess the changes of biomarker-KRAS(20 months)