A Phase 1a/1b Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of the CDK4 Inhibitor BGB-43395, Alone or as Part of Combination Therapies in Chinese Patients With Advanced or Metastatic HR+/HER2- Breast Cancer and Other Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 33
- 试验地点
- 7
- 主要终点
- Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
This is an open-label, multicenter, phase 1a/1b clinical study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of BGB-43395, a cyclin-dependent kinase 4 (CDK4) inhibitor, as monotherapy or in combination with fulvestrant, letrozole, or other combination partners in Chinese participants with hormone receptor positive (HR+) and human epidermal growth factor 2 negative (HER2-) breast cancer (BC) and other advanced or metastatic solid tumors.
详细描述
Our company, previously known as BeiGene, is now officially BeOne Medicines. Because some of our older studies were sponsored under the name BeiGene, you may see both names used for this study on this website.
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
- •Phase 1a (Dose Escalation): Participants with histologically or cytologically confirmed locally advanced or metastatic solid tumors associated with CDK4 dependency, including HR+/HER2- breast cancer. Participants must have received prior standard-of-care therapies for their disease, unless the therapy is not available or not tolerated, or is determined not appropriate based on the investigator's judgment.
- •Phase 1b (Dose Expansion): Participants with selected solid tumors including locally advanced or metastatic HR+/HER2- breast cancer.
- •Female participants with metastatic HR+/HER2- breast cancer will be required to have ovarian function suppression using gonadotropin-releasing hormone (GnRH) agonists such as goserelin or be postmenopausal.
- •Male participants with HR+/HER2- breast cancer will be required to have gonadal suppression using GnRH agonists when being treated with letrozole or fulvestrant.
- •Patients must have ≥1 measurable lesion per RECIST v1.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status ≤
- •Adequate organ function without symptomatic visceral disease.
排除标准
- •Prior therapy selectively targeting CDK4 (prior CDK4/6 inhibitor therapy is permitted).
- •Known leptomeningeal disease or uncontrolled untreated brain metastasis.
- •Any malignancy ≤ 3 years before the first dose of study drug(s) except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated with curative intent (eg, resected basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast).
- •Uncontrolled diabetes.
- •Infection requiring systemic antibacterial, antifungal, or antiviral therapy ≤ 28 days before the first dose of study drug(s), or symptomatic COVID-19 infection. Patients receiving prophylactic antibiotics (eg, for prevention of urinary tract infection, chronic obstructive pulmonary disease, or for dental extraction) are eligible. Patients who have recovered from symptomatic COVID-19 infection can be rescreened for this study.
- •Untreated chronic hepatitis B or active hepatitis C infection.
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Phase 1a: Dose Escalation
Sequential cohorts of increasing dose levels of BGB-43395 will be evaluated as monotherapy and in combination with either fulvestrant or letrozole.
干预措施: BGB-43395 (Drug)
Phase 1a: Dose Escalation
Sequential cohorts of increasing dose levels of BGB-43395 will be evaluated as monotherapy and in combination with either fulvestrant or letrozole.
干预措施: Fulvestrant (Drug)
Phase 1a: Dose Escalation
Sequential cohorts of increasing dose levels of BGB-43395 will be evaluated as monotherapy and in combination with either fulvestrant or letrozole.
干预措施: Letrozole (Drug)
Phase 1b: Dose Expansion
The recommended dose for expansion (RDFE) for BGB-43395 in combination with fulvestrant from Phase 1a will be evaluated in HR+ breast cancer and selected tumor cohorts.
干预措施: BGB-43395 (Drug)
Phase 1b: Dose Expansion
The recommended dose for expansion (RDFE) for BGB-43395 in combination with fulvestrant from Phase 1a will be evaluated in HR+ breast cancer and selected tumor cohorts.
干预措施: Fulvestrant (Drug)
结局指标
主要结局
Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: Up to approximately 30 months
Number of participants with AEs and SAEs including findings from physical examinations, electrocardiograms (ECGs), and laboratory assessments as needed, and that meet protocol-defined dose-limiting toxicity (DLT) criteria.
Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BGB-43395
时间窗: Up to approximately 30 months
MTD is defined as the highest dose evaluated for which estimated toxicity rate is the closest to the target toxicity rate. MAD is defined as the highest dose administered if MTD is not reached.
Phase 1a: Recommended Dose for Expansion (RDFE) of BGB-43395
时间窗: Up to approximately 30 months
RDFE of BGB-43395 alone or as part of combination therapies will be determined based upon the MTD or MAD.
Phase 1b: Objective Response Rate (ORR)
时间窗: Up to approximately 30 months
ORR is defined as the percentage of participants who have confirmed complete response (CR) or partial response (PR) as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
次要结局
- Phase 1a: ORR(Up to approximately 30 months)
- Phase 1b: Progression-Free Survival (PFS)(Up to approximately 30 months)
- Phase 1b: Number of Participants with AEs and SAEs(Up to approximately 30 months)
- Phase 1a and 1b: Duration of Response (DOR)(Up to approximately 30 months)
- Phase 1a and 1b: Time to Response (TTR)(Up to approximately 30 months)
- Phase 1b: Disease Control Rate (DCR)(Up to approximately 30 months)
- Phase 1b: Clinical Benefit Rate (CBR)(Up to approximately 30 months)
- Phase 1a: Observed plasma maximum concentration (Cmax) of BGB-43395 and its metabolite(From Cycle 1 Day 1 up to Cycle 7 Day 1 (each cycle is 28 days))
- Phase 1a: Observed plasma trough concentration (Ctrough) of BGB-43395 and its metabolite(From Cycle 1 Day 1 up to Cycle 7 Day 1 (each cycle is 28 days))
- Phase 1a: Area under the concentration-time curve (AUC) of BGB-43395 and its metabolite(From Cycle 1 Day 1 up to Cycle 7 Day 1 (each cycle is 28 days))
- Phase 1a: Half-life (t1/2) of BGB-43395 and its metabolite(From Cycle 1 Day 1 up to Cycle 7 Day 1 (each cycle is 28 days))
- Phase 1b: Plasma concentrations of BGB-43395 and its metabolite(From Cycle 1 Day 1 up to Cycle 5 Day 1 (each cycle is 28 days))