A Phase 2 Open-Label, Multicenter Study to Evaluate Efficacy and Safety of ZN‑c3 in Subjects with High-Grade Serous Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 194
- 试验地点
- 35
- 主要终点
- Part 1b: • Frequency and severity of TEAEs • Incidence of dose interruptions, dose reductions, and permanent discontinuations of ZN-c3 azenosertib due to related TEAEs
研究概览
简要总结
Part 1b: • To determine the safety and tolerability of azenosertib in subjects with PROC Part 2a: • To investigate the antitumor activity of 2 dose levels of azenosertib in subjects with cyclin E1-positive PROC • To investigate the safety and tolerability of 2 dose levels of azenosertib in subjects with cyclin E1-positive PROC
Part 2b: • To investigate the antitumor activity of azenosertib in subjects with cyclin E1-positive PROC at the selected dose
研究设计
- 分配方式
- Not Applicable
- 主要目的
- Follow-up Period
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Provision of signed ICF
- •Female Age ≥18 years (or age of majority in local region) at the time of informed consent.
- •Histologically or cytologically confirmed recurrent, high-grade serous ovarian, fallopian tube, or primary peritoneal cancer
- •Subject must have platinum-resistant disease
- •Subjects must have received 1-3 prior lines of therapy (up to 4 if prior mirvetuximab) for Part 2 (up to 4 if prior mirvetuximab)
- •Prior mirvetuximab is required if approved and available for eligible subjects
- •Subjects must have at least one measurable lesion as defined by RECIST Guideline Version 1.1
- •Performance Status: Eastern Cooperative Oncology Group (ECOG) score of ≤
- •Adequate hematologic and organ function during the Screening Period For the complete Inclusion Criteria, please refer to the study protocol
排除标准
- •Platinum refractory disease (in front line therapy)
- •Any of the following treatment interventions within the specified time frame prior to Cycle 1 Day 1 (C1D1): a. Hospitalization for any reason within 14 days c. Any chemotherapy or targeted tumor therapy within 14 days or 5 half-lives (whichever is shorter); d. Radiation therapy within 21 days; however, if the radiation portal covered ≤5% of the bone marrow, the subject is eligible irrespective of the end date of radiotherapy. e. Autologous or allogeneic stem cell transplant within 3 months. f. Current use of any other investigational drug therapy <28 days or 5 half-lives (whichever is shorter).
- •Prior therapy with azenosertib or any other WEE1 inhibitor, ATR inhibitor, CHK1/2 inhibitor, or PKMYT1 inhibitor.
- •A serious illness or medical conditions, listed in study protocol, including:
- •Unresolved toxicity of Grade >1 attributed to any prior therapies (excluding Grade ≤2 neuropathy, alopecia or skin pigmentation). For the complete Exclusion Criteria, please refer to the study protocol
结局指标
主要结局
Part 1b: • Frequency and severity of TEAEs • Incidence of dose interruptions, dose reductions, and permanent discontinuations of ZN-c3 azenosertib due to related TEAEs
Part 1b: • Frequency and severity of TEAEs • Incidence of dose interruptions, dose reductions, and permanent discontinuations of ZN-c3 azenosertib due to related TEAEs
Part 2a: Independent primary endpoints: ORR as defined by RECIST v1.1 and as assessed by the Investigator in subjects with centrally determined cyclin E1-positive status • Frequency and severity of TEAEs
Part 2a: Independent primary endpoints: ORR as defined by RECIST v1.1 and as assessed by the Investigator in subjects with centrally determined cyclin E1-positive status • Frequency and severity of TEAEs
Part 2b: • ORR as defined by RECIST v1.1 and as assessed by ICR in subjects with centrally determined cyclin E1-positive status
Part 2b: • ORR as defined by RECIST v1.1 and as assessed by ICR in subjects with centrally determined cyclin E1-positive status
次要结局
- Part 1b: • Summarized by cohort and overall: o ORR, DOR, TTR, PFS, and CBR as defined by RECIST v1.1 and as assessed by ICR and the Investigator o OS o CA-125 response by GCIG criteria • Plasma concentrations of azenosertib
- Part 2a: • DOR, TTR, PFS, and CBR as defined by RECIST v1.1 and as assessed by the Investigator • OS • CA-125 response by GCIG criteria • ORR and DOR as defined by RECIST v1.1 and as assessed by the Investigator • Systemic plasma concentrations of azenosertib
- Part 2b: • Frequency and severity of TEAEs • ORR, DOR, TTR, PFS, and CBR as defined by RECIST v1.1 as assessed by the Investigator • DOR, TTR, PFS, and CBR as defined by RECIST v1.1 as assessed by ICR • OS • CA-125 response by GCIG criteria • ORR and DOR as defined by RECIST v1.1 as assessed by the Investigator
研究者
Head of Medical Affairs
Scientific
K-Group Beta Inc.