A Phase 1/2 Dose-Escalation and Dose-Expansion Study of ZN-c3 in Combination with Niraparib and ZN-c3 Monotherapy in Subjects with Platinum-resistant Ovarian Cancer.
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 150
- 试验地点
- 6
- 主要终点
- ZN-c3 with niraparib: • Phase 1: Frequency and severity of dose-limiting toxicities (DLTs) in DLT-evaluable subjects during Cycle 1 (C1).
研究概览
简要总结
ZN-c3 in combination with niraparib: • Phase 1b: To investigate the safety and tolerability of ZN-c3 in combination with niraparib, including identification of the MTD and RP2D • Phase 2: To investigate the antitumor activity of ZN-c3 in combination with niraparib ZN-c3 monotherapy: • To determine the safety and tolerability of ZN-c3 monotherapy • To investigate the antitumor activity of ZN-c3 monotherapy
研究设计
- 分配方式
- Randomized
- 主要目的
- Zn-c3 Monotherapy
- 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
- •Histologically or cytologically confirmed recurrent high grade epithelial ovarian, primary peritoneal, or fallopian tube cancer with histologic subtypes of serous, clear cell or endometroid for which there is no known or established treatment available with curative intent.
- •Subjects must have platinum-resistant disease.
- •Must have evaluable or measurable disease according to RECIST v1.1 criterion: defined as at least one lesion that can be accurately measured.
- •Adequate hematologic and organ function.
- •Ability and willingness to take oral medication.
- •Subjects must provide formalin-fixed, paraffin-embedded tumor samples available from the primary or recurrent cancer.
排除标准
- •Major surgery within 28 days (any surgical incision should be fully healed prior to study drug administration).
- •Any chemotherapy or targeted tumor therapy within 14 days or 5 half-lives (whichever is shorter)
- •A minimum of 10 days between termination of the prior PARPi and administration of ZN-c3 and niraparib treatment is required.
- •Any investigational drug therapy <28 days.
- •Prior treatment with a WEE1 inhibitor.
- •Known hypersensitivity to any drugs similar to ZN-c3 and/or niraparib in class or its excipients.
- •Participant has any known history or current diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
- •Uncontrolled hypertension (Diastolic BP > 90 mmHg or Systolic BP > 140 mmHg).
- •Myocardial impairment of any cause (e.g., cardiomyopathy, ischemic heart disease, significant valvular dysfunction, hypertensive heart disease, and congestive heart failure) resulting in heart failure by New York Heart Association Criteria (Class III or IV). Significant gastrointestinal abnormalities, 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.
结局指标
主要结局
ZN-c3 with niraparib: • Phase 1: Frequency and severity of dose-limiting toxicities (DLTs) in DLT-evaluable subjects during Cycle 1 (C1).
ZN-c3 with niraparib: • Phase 1: Frequency and severity of dose-limiting toxicities (DLTs) in DLT-evaluable subjects during Cycle 1 (C1).
• Phase 2: – Stage 1 (Futility): Progression-free survival (PFS) at 4 months as defined by the revised Response Evaluation Criteria in Solid Tumors (RECIST) Guideline version 1.1. – Stage 2 (Promising Clinical Activity): Objective response rate (ORR) as defined by the revised RECIST Guideline version 1.1 and assessed by Independent Central Review (ICR).
• Phase 2: – Stage 1 (Futility): Progression-free survival (PFS) at 4 months as defined by the revised Response Evaluation Criteria in Solid Tumors (RECIST) Guideline version 1.1. – Stage 2 (Promising Clinical Activity): Objective response rate (ORR) as defined by the revised RECIST Guideline version 1.1 and assessed by Independent Central Review (ICR).
ZN-c3 monotherapy: • Frequency and severity of adverse events (AEs), including laboratory abnormalities, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. • Incidence of dose interruptions, dose reductions, and permanent treatment discontinuations due to treatment-related AEs • ORR as defined by the revised RECIST Guideline version 1.1 and assessed by ICR.
ZN-c3 monotherapy: • Frequency and severity of adverse events (AEs), including laboratory abnormalities, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. • Incidence of dose interruptions, dose reductions, and permanent treatment discontinuations due to treatment-related AEs • ORR as defined by the revised RECIST Guideline version 1.1 and assessed by ICR.
次要结局
- ORR based on Investigator assessment using RECIST v 1.1
- OS (median at 12 months and overall)
- • Duration of response (DOR) as a key secondary endpoint
- Clinical benefit rate (CBR), PFS (median and 4-month rate), as defined by the revised RECIST Guideline version 1.1.
- Frequency and severity of AEs, including laboratory abnormalities, graded according to the NCI-CTCAE version 5.0.
- Incidence of dose interruptions, dose reductions, and permanent treatment discontinuations due to treatment-related AEs
- Ongoing measurement of subject-reported symptomatic toxicity according to the PRO-CTCAE, and determination of change from Baseline in self-reported quality of life using EQ-5D-5L
- Plasma PK parameters of ZN-c3 (and its potential metabolites, as applicable) and niraparib.
研究者
Head of Regulatory Affairs
Scientific
K-Group Beta Inc.