A First-in-Human, Open-Label, Dose Escalation and Expansion Trial of BTX-9341 in Participants With Advanced and/or Metastatic Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 82
- 试验地点
- 1
- 主要终点
- Safety and Tolerability of BTX-9341
研究概览
简要总结
The purpose of this study is to test BTX-9341 alone or in combination with fulvestrant (a currently marketed medication for breast cancer) in participants with advanced and/or metastatic hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer. The study includes a dose escalation part (Part A) where small groups of participants will receive increasing doses of BTX-9341 or BTX-9341 + fulvestrant followed by a dose expansion part (Part B) where participants will receive the dose of BTX-9341 selected in Part A + fulvestrant.
详细描述
This first-in-human (FIH), Phase 1 study of BTX-9341 is multicenter, nonrandomized, and open-label to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of BTX-9341 in participants with advanced and/or metastatic HR+/HER2 breast cancer. The study will include a dose escalation part (Part A) followed by a dose expansion part (Part B). During Part A, BTX-9341 will initially be dose escalated alone and then in combination with fulvestrant. A single combination therapy cohort of BTX-9341 + fulvestrant will be further explored in Part B. BTX-9341 will be administered orally in 28-day treatment cycles.
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
- •Metastatic and/or locally advanced HR+/HER2- breast cancer (dose escalation: measurable disease and/or at least 1 lytic or mixed [lytic + sclerotic] bone lesion that can be assessed by CT or MRI or non-measurable disease [including bone lesions]; dose expansion: measurable disease)
- •Dose escalation: (a) received not more than 1 chemotherapy in the metastatic/advanced setting; (b) no limit to the lines of endocrine therapy (monotherapy or combination therapy) in the metastatic setting; (c) received CDK4/6 inhibitor therapy
- •Dose expansion: (a) received not more than 1 chemotherapy in metastatic/advanced setting; (b) received not more than 2 lines of endocrine therapy (monotherapy or combination therapy) and must have been on prior endocrine therapy for at least 6 months before progression; (c) received at most 2 lines of CDK4/6 inhibitor therapy (1 in the adjuvant setting and 1 in the metastatic setting) and must have been on prior CDK4/6 inhibitor therapy for at least 6 months
- •Acceptable hematologic function
- •ANC ≥ 1500 per mL. Note: Use of growth-factors to maintain the ANC criterion is prohibited.
- •Platelet count ≥ 100,000 per mL. Note: Use of transfusions or thrombopoietic agents to achieve the baseline platelet count criterion is prohibited.
- •Hemoglobin ≥ 9.0 g/dL. Note: Packed red blood cell transfusion is allowed up to 14 days prior to trial entry.
- •Acceptable liver function
- •Bilirubin ≤ 2.0 × institutional upper limit of normal (ULN) (or < 3.0 × institutional ULN if Gilbert's disease is present)
- •Alanine transaminase (ALT)/aspartate aminotransferase (AST) ≤ 3.0 × institutional ULN (≤ 5.0 × institutional ULN if liver metastases present)
- •Alkaline phosphatase ≤ 2.5 × institutional ULN (≤ 5.0 × institutional ULN if bone or liver metastases present)
- •Able and willing to sign informed consent
- •Meets all study requirements in the opinion of the Investigator
排除标准
- •RB1 (retinoblastoma) gene mutation
- •Symptomatic visceral disease
- •Clinical evidence or history of central nervous system metastasis
- •Abnormalities in coagulation, such as bleeding diathesis, or treatment with anticoagulants precluding injections of fulvestrant or luteinizing hormone-releasing hormone (LHRH) agonist
研究组 & 干预措施
BTX-9341 (Part A)
BTX-9341 capsule(s) administered orally once daily (QD) in 28-day cycles
干预措施: BTX-9341 (Drug)
BTX-9341 + fulvestrant (Part A)
BTX-9341 capsule(s) administered orally QD in 28-day cycles and fulvestrant intermuscular injections on Day 15 and then once every 28 days
干预措施: BTX-9341 (Drug)
BTX-9341 + fulvestrant (Part A)
BTX-9341 capsule(s) administered orally QD in 28-day cycles and fulvestrant intermuscular injections on Day 15 and then once every 28 days
干预措施: Fulvestrant (Drug)
BTX-9341 + fulvestrant (Part B)
BTX-9341 capsule(s) administered orally QD in 28-day cycles and fulvestrant intermuscular injections on Day 15 and then once every 28 days
干预措施: Fulvestrant (Drug)
BTX-9341 + fulvestrant (Part B)
BTX-9341 capsule(s) administered orally QD in 28-day cycles and fulvestrant intermuscular injections on Day 15 and then once every 28 days
干预措施: BTX-9341 (Drug)
结局指标
主要结局
Safety and Tolerability of BTX-9341
时间窗: Up to 28 days after last dose of BTX-9341
Frequency and severity, incidence of treatment-emergent and treatment-related adverse events using NCI-CTCAE v5.0
Part A: Number of Participants With Dose Limiting Toxicities (DLTs)
时间窗: 28 days
DLT rate in Cycle 1
Part A: Determine MTD/MED of BTX-9341 in monotherapy
时间窗: Approximately 1 year from study start
Based on CTCAE v5.0 assessment of adverse events
Part A: Determine MTD/MED of BTX-9341 in combination therapy
时间窗: Approximately 18 months from study start
Based on CTCAE v5.0 assessment of adverse events
Part B Combination Therapy: Objective Response (OR) rate
时间窗: Approximately 18 months from start of Part B
OR is the confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1 as determined by Investigator assessment
次要结局
未报告次要终点