NCT07546500招募中3 期
A Randomized, Open-Label Phase 3 Study of Azenosertib Versus Investigator's Choice of Chemotherapy in Platinum-Resistant High-Grade Serous Ovarian, Primary Peritoneal, or Fallopian Tube Cancers Positive for Cyclin E1 Protein Expression
K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc61 个研究点 分布在 11 个国家目标入组 420 人开始时间: 2026年4月17日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 420
- 试验地点
- 61
- 主要终点
- Progression free survival (PFS) per RECIST v1.1 as assessed by Investigator
研究概览
简要总结
This is a randomized, Phase 3 trial designed to evaluate the efficacy and safety of azenosertib compared to Investigator's choice of chemotherapy in subjects with platinum-resistant ovarian cancer whose tumors are positive for cyclin E1 protein expression.
详细描述
A Phase 3 study to evaluate the efficacy, safety, and overall clinical benefit of azenosertib (ZN-c3) compared with Investigator's choice of chemotherapy in subjects with Platinum-Resistant, High-Grade Serous Ovarian, Fallopian Tube, or Primary Peritoneal Cancer. Azenosertib is a selective and orally bioavailable inhibitor of WEE1. In HGSOC, high Cyclin E1 protein drives replication stress and increases tumor reliance on WEE1-mediated G2/M checkpoint control. Treating tumor cells with azenosertib promotes premature cell cycle progression leading to increased replication stress and accumulation of DNA damage pushing cells to mitotic catastrophe resulting in tumor cell death.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- Female
- 接受健康志愿者
- 否
入选标准
- •Female age ≥ 18 years
- •High-grade serous epithelial ovarian, primary peritoneal, or fallopian tube cancer
- •Measurable disease per RECIST Version 1.1
- •Eastern Cooperative Oncology Group (ECOG) performance status score 0-1
- •The subject's tumor tissue must be positive for cyclin E1 protein expression per the Sponsor's clinically validated cyclin E1 IHC investigational, in vitro diagnostic assay
- •Prior Therapy:
- •Subject must have platinum-resistant disease
- •One to 3 prior lines or regimens are allowed (1 to 4 prior lines are permitted, if prior mirvetuximab)
- •Prior bevacizumab treatment is required, if eligible per standard of care
- •Prior PARP inhibitor treatment is required if BRCA 1/2 mutation or HRD, if eligible per standard of care
- •Prior mirvetuximab treatment is required, if eligible per standard of care
- •Adequate hematologic and organ function during the screening period
排除标准
- •History of another malignancy in the previous 2 years, unless cured by surgery alone and continuously disease-free. Exceptions include appropriately treated carcinoma in situ of the cervix, nonmelanoma skin carcinoma, Stage 1 uterine cancer, or other malignancies with an expected curative outcome.
- •Subjects with primary platinum-refractory disease.
- •Prior therapy with azenosertib or any other WEE1 inhibitor, ATR inhibitor, CHK1/2 inhibitor, or (PKMYT1) inhibitor for PROC.
- •A serious illness or medical condition(s) including, but not limited to, the following:
- •Clinically or radiographically unstable brain metastases or leptomeningeal disease that requires immediate treatment. Subjects with asymptomatic brain metastases are eligible.
- •Acute kidney injury requiring intervention, or presence of indwelling urinary catheter or percutaneous nephrostomy.
- •Significant gastrointestinal abnormalities, including an inability to take oral medication, requirement for IV alimentation, active peptic ulcer, chronic diarrhea or vomiting considered to be clinically significant in the judgment of the Investigator, or prior surgical procedures affecting absorption.
- •Any evidence of small bowel obstruction as determined by air/fluid levels on computed tomography (CT) scan, recent hospitalization for small bowel obstruction within 3 months before randomization, or recurrent paracentesis or thoracentesis within 6 weeks before randomization.
- •Active, uncontrolled infection. Subjects with an infection receiving treatment (antibiotic, antifungal, or antiviral) must have completed such treatment and the infection must be considered controlled/resolved (and afebrile) by the Investigator for at least 7 days before randomization
- •Myocardial impairment of any cause resulting in heart failure by New York Heart Association criteria (Class II, III or IV).
- •Medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or may interfere with the interpretation of study results
- •Any of the following treatment interventions within the specified time frame before randomization:
- •Hospitalization within 14 days
- •Major surgery within 28 days
- •Any chemotherapy or targeted tumor therapy within 21 days or 5 half-lives (whichever is shorter)
- •Radiation therapy within 21 days
- •Autologous or allogeneic stem cell transplant within 3 months
- •Current use of any other investigational drug therapy < 28 days or 5 half-lives (whichever is shorter)
- •Inability to discontinue treatment with prescription or nonprescription drugs that are prohibited per protocol.
- •Inability to discontinue consumption of food and herbal supplements that are prohibited per protocol
- •Prior wide-field radiotherapy affecting ≥ 20% of the bone marrow.
- •Unresolved toxicity of Grade > 1 attributed to any prior therapies (excluding Grade ≤ 2 neuropathy, alopecia, or skin pigmentation).
- •Subjects who are immunocompromised or HIV-positive on highly active anti-retroviral therapy
- •Subjects with known active hepatitis B or hepatitis C infection
- •Individuals who are judged by the Investigator to be unsuitable as study subjects
研究组 & 干预措施
Experimental: Arm C Investigator's choice of chemotherapy at the dose defined by the protocol
Active Comparator
干预措施: Investigator's choice of Chemotherapy (Drug)
Arm A Azenosertib 400 mg administered daily on a 5 days on, 2 days off intermittent schedule
Experimental
干预措施: Azenosertib (Drug)
结局指标
主要结局
Progression free survival (PFS) per RECIST v1.1 as assessed by Investigator
时间窗: Up to approximately 24 months from the enrollment of the last subject
Time from randomization to the first documented tumor progression (per RECIST v1.1) or death from any cause, whichever occurs first.
次要结局
- Overall survival(Up to approximately 24 months from the enrollment of the last subject)
- PFS per RECIST 1.1 as assessed by blinded independent central review (ICR)(Up to approximately 24 months from the enrollment of the last subject)
- Objective Response Rate (ORR) per RECIST v1.1 and assessed by Investigator(Up to approximately 24 months from the enrollment of the last subject)
- Change from baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire score (EORTC QLQ)-Core 30 (C30) at each post baseline visit(Up to approximately 24 months from the enrollment of the last subject)
- Change from baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire score (EORTC QLQ)-OV28 at each post baseline visit(Up to approximately 24 months from the enrollment of the last subject)
- Change from baseline in EQ-5D-5L score at each post baseline visit(Up to approximately 24 months from the enrollment of the last subject)
- Number of Subjects experiencing treatment emergent adverse events (TEAEs)(Up to approximately 24 months and 30 days from the enrollment of the last subject)
研究者
研究点 (61)
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