A Phase 1/2 Open Label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, and Anti-Tumor Activity of ZN-c5 Alone and in Combination With Palbociclib in Subjects With Estrogen-Receptor Positive, Human Epidermal Growth Factor Receptor-2 Negative Advanced Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 181
- 试验地点
- 38
- 主要终点
- Clinical Benefit Rate (CBR) for ZN-c5 as a Monotherapy
研究概览
简要总结
This is a Phase 1/2, open-label, multicenter, dose-escalation and expansion study to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of ZN-c5 administered orally in subjects with advanced estrogen receptor positive, human epidermal growth factor receptor 2 negative (ER+/HER2-) breast cancer. ZN-c5 will be evaluated both as monotherapy and in combination with palbociclib (IBRANCE®).
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
- •Age ≥ 18 years of age
- •Women can be postmenopausal, as defined by at least one of the following:
- •Age ≥ 60 years;
- •Age < 60 years and cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and serum estradiol and follicle-stimulating hormone level within the laboratory's reference range for postmenopausal females;
- •Documented bilateral oophorectomy; or can be peri- or premenopausal, however, they must receive a gonadotrophin-releasing hormone agonist beginning at least 4 weeks prior to the first dose of study medication.
- •Histologically or cytologically confirmed diagnosis of advanced (metastatic or locoregionally recurrent) 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
- •Documented prior response to endocrine therapy for metastatic disease (stable disease, partial response, or complete response by RECIST v1.1 criteria) lasting > 6 months
- •Evaluable or measurable disease by RECIST v1.
- •Tumor lesions previously irradiated or subjected to other locoregional therapy will only be deemed measurable if progression at the treated site after completion of therapy is clearly documented.
排除标准
- •Prior anticancer or investigational drugs for the treatment of ER+/HER2 negative advanced breast cancer within the following windows:
- •Tamoxifen, aromatase inhibitor, fulvestrant, or other anti-cancer endocrine therapy < 14 days before first dose of study treatment
- •Any chemotherapy < 28 days before first dose of study, except for Phase 2 monotherapy which requires no prior chemotherapy treatment.
- •Any investigational drug therapy < 28 days or 5 half-lives (whichever is shorter) prior to first dose of study treatment
- •Unexplained symptomatic endometrial disorders (including, but not limited to endometrial hyperplasia, dysfunctional uterine bleeding, or cysts)
研究组 & 干预措施
ZN-c5 + palbociclib combination therapy
Dose escalation cohorts are planned to determine maximum tolerated dose(MTD) or recommended phase 2 dose (RP2D) of ZN-c5 in combination with palbociclib as well as a Phase 2 cohort.
干预措施: Palbociclib (Drug)
ZN-c5 monotherapy
Dose escalation cohorts are planned to determine maximum tolerated dose(MTD) or recommended phase 2 dose (RP2D) of ZN-c5 as well as expansion cohorts and a Phase 2 cohort.
干预措施: ZN-c5 (Drug)
ZN-c5 + palbociclib combination therapy
Dose escalation cohorts are planned to determine maximum tolerated dose(MTD) or recommended phase 2 dose (RP2D) of ZN-c5 in combination with palbociclib as well as a Phase 2 cohort.
干预措施: ZN-c5 (Drug)
结局指标
主要结局
Clinical Benefit Rate (CBR) for ZN-c5 as a Monotherapy
时间窗: 24 weeks
CBR is defined as the number of participants who have at least 1 confirmed response of complete response (CR) or partial response (PR) (only if participant has measurable disease), or stable disease (SD) \>= 24 weeks (or non-CR/non-progressive disease (PD) \>=24 weeks for participants with non-measurable disease) prior to any evidence of progression.
Best Overall Response (BOR) for ZN-c5 as a Monotherapy
时间窗: 24 weeks
Best overall response was summarized categorically based on the four RECIST categories: CR, PR, SD and PD.
次要结局
- Monotherapy Only: Percentage of Participants With Progression-Free Survival at 8 Months(8 months)
- Monotherapy Only: Percentage of Participants With Overall Survival at 4 Months(4 months)
- Monotherapy Only: Percentage of Participants With Overall Survival at 8 Months(8 months)
- Monotherapy Only: Percentage of Participants With Overall Survival at 12 Months(12 months)
- Monotherapy Only: Percentage of Participants With Progression-Free Survival (PFS) at 2 Months(2 months)
- Monotherapy Only: Percentage of Participants With Progression-Free Survival at 4 Months(4 months)
- Monotherapy Only: Percentage of Participants With Progression-Free Survival at 6 Months(6 months)
- Monotherapy Only: Percentage of Participants With Overall Survival (OS) at 2 Months(2 months)
- Monotherapy Only: Percentage of Participants With Overall Survival at 6 Months(6 months)
- Monotherapy Only: Percentage of Participants With Overall Survival at 10 Months(10 months)
- Objective Response Rate (ORR) for ZN-c5 as a Monotherapy(24 weeks)
- Monotherapy Only: Percentage of Participants With Progression-Free Survival at 10 Months(10 months)
- Monotherapy Only: Percentage of Participants With Progression-Free Survival at 12 Months(12 months)