A Dose-confirming Study of CFI-402257 as a Single Agent in Advanced Solid Tumors and in Combination With Fulvestrant in Patients With ER+/HER2- Advanced Breast Cancer After Disease Progression on Prior CDK4/6 and Endocrine Therapy
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 44
- 试验地点
- 4
- 主要终点
- To assess the incidence of adverse events of CFI-402257 as a single agent and at the recommended phase 2 dose (RP2D)
研究概览
简要总结
The purpose of this study is to test the safety of an investigational drug called CFI-402257 alone in advanced solid tumors and in combination with Fulvestrant in advanced breast cancer patients.
详细描述
This study will be evaluating the safety and tolerability of CFI-402257 in subjects with advanced solid tumors and in advanced breast cancer. The study is designed to build on encouraging data from another study and to obtain further safety, efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) data of CFI-402257.
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 Escalation
- •Have histological or cytological proof of advanced cancer that has progressed on at least 1 prior line of systemic therapy
- •Inclusion Criteria: Part A Expansion
- •Breast cancer patients positive for estrogen receptor and/or progesterone receptor and negative for HER2
- •Must have previously received a CDK4/6 inhibitor
- •No limit on lines of endocrine therapy
- •Must have received no more than 1 line of cytotoxic chemotherapy
- •Have measurable disease as per RECIST 1.1 guidelines.
- •Inclusion Criteria: Part B
- •Breast cancer patients positive for estrogen receptor and/or progesterone receptor and negative for HER2
- •Must have previously received a CDK4/6 inhibitor
- •Must have previously received no more than 1 line of endocrine therapy
- •Must have received no more than 1 line of cytotoxic chemotherapy
- •Have measurable disease as per RECIST 1.1 guidelines.
排除标准
- •Are pregnant or nursing.
- •Have received chemotherapy, biological therapy, or investigational treatment less than 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to first dose of study drug. Have received radiotherapy less than 2 weeks prior to first dose of study drug.
- •Received growth factors within 14 days prior to initiation of dosing of CFI-402257 or who will require ongoing treatment with growth factors
- •Have active, acute, or clinically significant chronic infections.
- •Have the following cardiovascular conditions
- •Have uncontrolled severe hypertension
- •Have symptomatic congestive heart failure
- •Have active angina pectoris or recent myocardial infarction
- •Have chronic atrial fibrillation or QTc of greater than 470 msec.
- •Have had major surgery within 21 days of starting therapy.
- •Primary central nervous system malignancies or known central nervous system metastasis.
- •Being treated with full dose warfarin.
- •Coagulopathy or any history of coagulopathy within the past 6 months, including history of deep vein thrombosis or pulmonary embolism.
- •Patients must avoid the use of strong CYP3A4 inducers and inhibitors. CYP3A sensitive substrates, PgP, BCRP inhibitors
- •Have had prior treatment with a TTK/MPS1 inhibitor.
- •Part B only: Known bleeding disorder which would prohibit administration of fulvestrant.
- •Part B only: Concomitant active malignancy other than ER+/HER2- advanced breast cancer.
- •Part A only: Concomitant active malignancy other than primary malignancy
- •Part B only: Had prior treatment with fulvestrant or agents with similar MoA
研究组 & 干预措施
Part A: Monotherapy Escalation and Expansion
Dose selection and expansion of CFI-402257
干预措施: CFI-402257 (Drug)
Part B: Combination Escalation and Expansion
Dose selection and expansion of CFI-402257 with Fulvestrant
干预措施: CFI-402257 (Drug)
Part B: Combination Escalation and Expansion
Dose selection and expansion of CFI-402257 with Fulvestrant
干预措施: Fulvestrant (Drug)
结局指标
主要结局
To assess the incidence of adverse events of CFI-402257 as a single agent and at the recommended phase 2 dose (RP2D)
时间窗: 48 months
The number of subjects who experience an adverse event that was possibly related to study drug as assessed by CTCAE v 5.0.
To assess the incidence of adverse events of CFI-402257 in combination with fulvestrant and at the recommended phase 2 dose (RP2D)
时间窗: 48 months
The number of subjects who experience an adverse event that was possibly related to study drug as assessed by CTCAE v 5.0.
次要结局
- Assessment of objective response rates(48 months)
- Assessment of objective response rates of the combination(48 months)
- Assessment of the pharmacokinetic profile of CFI-402257 in combination with fulvestrant through AUC(48 months)
- Assessment of the pharmacokinetic profile of CFI-402257 through AUC(48 months)
- To evaluate the effect of CFI-402257 treatment on changes in variant allele function(48 months)