A PHASE 1B STUDY TO ASSESS THE SAFETY AND TOLERABILITY OF ZN-C5 IN CHINESE SUBJECTS WITH ADVANCED BREAST CANCER
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Incidence of treatment-emergent adverse events
研究概览
简要总结
The aim of this phase 1b study in Chinese patients with ER+/Her2- advanced breast cancer is to evaluate the safety and tolerability of ZN-c5 at dose of 50 mg and 150 mg QD well tolerance established in the previous oversea study in non-Chinese patients.
详细描述
Hormone receptor-positive, HER2-negative breast cancer is the most common subset of breast cancer. The estrogen receptor (ER) in these patients is a key driver of disease progression, and the primary reason for relapse in these patients is that endocrine therapies are only partially effective, typically causing cell cycle arrest rather than cell death. As a result, secondary resistance to endocrine therapy is a major clinical challenge. ZN-c5 is a novel and potent ZN-c5 is a novel and potent selective estrogen receptor degrader with oral bioavailability and strong activity in estrogen-dependent and tamoxifen-resistant tumor models.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Male or female
- •Age ≥ 18 years
- •Menopausal Status [Female subjects]
- •Histologically or cytologically confirmed diagnosis of advanced adenocarcinoma of the breast, not amenable to any potential curative intervention
- •Estrogen Receptor (ER) positive disease
- •Human Epidermal Growth Factor Receptor 2 (HER2) negative disease
- •Refractory to or intolerant of established therapy(ies) known to provide clinical benefit for their malignancy
- •Prior Hormonal Therapy:
- •Documented prior response to endocrine therapy for advanced or metastatic disease (SD, PR, or CR) lasting > 6 months24 weeks or disease recurrence after at least 24 months of adjuvant endocrine treatment.
- •Prior Chemotherapy: Up to 2 prior lines of chemotherapy for the treatment of advanced breast cancer
- •Prior treatment with a CDK4/6 inhibitor is allowed
- •Evaluable or measurable disease per RECIST v1.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1
- •All acute toxic effects of any prior anti-tumor therapy resolved to Grade ≤ 1 or baseline (with the exception of alopecia [any grade permitted])
- •Adequate organ function
- •[Premenopausal and perimenopausal female subjects]: Negative serum pregnancy test
- •Male and female subjects of childbearing potential or partners of subjects who engage in intercourse must agree to use protocol specified method(s) of contraception.
排除标准
- •Any of the following within the specified window prior to the first dose of study drug
- •Prior hematopoietic stem cell or bone marrow transplantation
- •Prior radiotherapy to > 25% of bone marrow
- •Brain metastases that require immediate treatment or are clinically or radiologically unstable (i.e., have been stable for < 1 month). If receiving steroids, subjects must be receiving a stable to decreasing corticosteroid dose during at least 1 week before enrollment.
- •Leptomeningeal disease that requires or is anticipated to require immediate treatment.
- •Presence of life-threatening metastatic visceral disease or symptomatic pulmonary lymphangitic spread
- •Other known active cancer(s) likely to require treatment in the next year that would impact the assessment of any study endpoints
- •[Female subjects]: Pregnant or breast-feeding
- •Unexplained symptomatic endometrial disorders (including, but not limited to endometrial hyperplasia, dysfunctional uterine bleeding, or cysts)
- •Impairment of gastrointestinal (GI) absorption for oral medications
- •Nausea, vomiting, or diarrhea > Grade 1
- •Myocardial infarction, symptomatic congestive heart failure (NYHA > Class II), unstable angina, or serious uncontrolled cardiac arrhythmia within the last 6 months
- •QTc interval > 480 msec (based on the mean value of the triplicate ECGs), family or personal history of long or short QT syndrome, Brugada syndrome or history of Torsade de Pointes
- •Concurrent use of food or drugs known to be moderate or strong CYP3A or CYP2C9 inducers and moderate or strong CYP3A4 or CYP2C9 inhibitors.
- •Positive serum virological tests (HBsAg, HCV-AB, HIV-AB, TP-AB) at screening stage will be excluded.
- •Any clinically significant disorder, condition, or disease that, in the opinion of the Investigator or Medical Monitor would pose a risk to subject safety or interfere with the study evaluations, procedures, or completion
研究组 & 干预措施
ZN-c5 50mg QD dose cohort
Phase 1b trial of monotherapy cohort with ZN-c5 as single agent will be evaluated with ZN-c5 50 mg administered orally, once daily. Safety lead in phase will be applied.
干预措施: ZN-c5 (Drug)
Zn-c5 150mg QD dose cohort
Once safety and tolerability are established in ZN-c5 150 mg Dose QD in Chinese population, then it is possible to initiate the second monotherapy cohort with 150 mg QD or alternative dose well established in oversea population for preliminary efficacy and safety.
干预措施: ZN-c5 (Drug)
结局指标
主要结局
Incidence of treatment-emergent adverse events
时间窗: until 30 days after the last dose of study drug
Investigate the safety and tolerability of dose of 150 mg QD of ZN-c5
Observed Dose Limited Toxicities (DLTs) in safety lead in phase
时间窗: At the end of Cycle 1 (each cycle is 28 days)
Safety lead in phase at dose of 50 mg QD: Determine a tolerated dose for ZN-c5 in monotherapy
次要结局
- bjective Response Rate (ORR)(2 year)
- CBR (CR [+ PR] + SD ≥ 24 weeks).(2 year)
- Duration of Response (DOR)(2 year)
- Progression-Free Survival (PFS)(2 year)