A Phase 1/1b Study Evaluating the Safety, Pharmacology, and Clinical Effect of ZH9 Treatment in Patients With Non-Muscle Invasive Bladder Cancer
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 22
- 试验地点
- 4
- 主要终点
- Incidence of dose-limiting toxicities
研究概览
简要总结
This is a first-in-human, multicenter, Phase 1/1b, 3-part, double-blind study of ZH9 in patients with recurrent NMIBC who are eligible for intravesical therapy. In Part 1, the safety, tolerability, and pharmacology of ZH9 IVI will be evaluated in a single ascending dose (SAD) patient cohort. In Part 2, the safety, tolerability, and pharmacology of ZH9 oral prime followed by ZH9 IVI will be evaluated in 2 patient cohorts at the doses and schedule established in Part 1. In Part 3, the safety, pharmacology, and clinical efficacy of ZH9 will be further evaluated in 2 expansion cohorts of patients with recurrent intermediate- and high-risk NMIBC.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
盲法说明
All administrations of ZH9 as an IVI will be open-label in Parts 1, 2, and 3. In Part 2 only, patients will be randomized 1:1 to receive either ZH9 or placebo oral prime. The oral priming condition will be conducted in a double-blind, placebo-controlled manner. The randomization list will only be made available to the unblinded pharmacist dispensing the study drug. At each clinical site, an unblinded pharmacist will be assigned to prepare the blinded study drug for administration (ZH9 oral prime or placebo).
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years
- •Histologically documented recurrence of NMIBC
- •BCG unresponsive (BCG naïve patients may be enrolled if they have received at least 1 line of adequate intravesical standard of care (SOC) treatment and are either not candidates for BCG or do not have access to BCG (e.g., BCG shortage))
- •Eastern Cooperative Oncology Group Performance Status 0-1
- •Adequate organ and marrow function
- •Highly effective contraception if risk of conception exists.
- •A female participant is eligible if not pregnant, not breastfeeding, not a woman of childbearing potential (WOCBP) or is a WOCBP that uses highly effective contraception.
排除标准
- •Received treatment with any local or systemic antineoplastic therapy within 3 weeks or 5× the plasma half-life prior to first dose of ZH9
- •Major surgery or radiation within the 3 weeks prior to Screening (TURBT is not considered major surgery)
- •Concurrent urinary tract infection or history of clinically significant polyuria
- •Symptoms consistent with typhoid
- •Evidence of infection within 2 weeks of the first dose of ZH9
- •Significant 12-lead electrocardiogram abnormalities
- •History of malignancy within the previous 12 months
- •History of allogeneic tissue/solid organ transplant
研究组 & 干预措施
Dose Level 1 - ZH9
Part 1 will evaluate SAD of ZH9 administered as an IVI in patients with recurrent NMIBC. A standard 3+3 escalation design will be employed with the dose levels
干预措施: ZH9 (Drug)
Dose Level 2 - ZH9
Part 1 will evaluate SAD of ZH9 administered as an IVI in patients with recurrent NMIBC. A standard 3+3 escalation design will be employed with the dose levels
干预措施: ZH9 (Drug)
Dose Level 3 - ZH9
Part 1 will evaluate SAD of ZH9 administered as an IVI in patients with recurrent NMIBC. A standard 3+3 escalation design will be employed with the dose levels
干预措施: ZH9 (Drug)
Dose Level 4 - ZH9
Part 1 will evaluate SAD of ZH9 administered as an IVI in patients with recurrent NMIBC. A standard 3+3 escalation design will be employed with the dose levels
干预措施: ZH9 (Drug)
结局指标
主要结局
Incidence of dose-limiting toxicities
时间窗: 28 days
Toxicity will be evaluated according to the NCI CTCAE Version 5.0
次要结局
- Rate of complete pathologic response(3, 6, and 12 months)
- Rate of recurrence-free survival and duration or response(3, 6, and 12 months)
- Rate of CR(6 and 12 months)
- Proportion of patients with cystectomy-free survival(6 and 12 months)
- Rate of progression-free survival(12 months)
- Overall response rate and recurrence-free rate(6 and 12 months)
- Change from baseline in systemic and local inflammatory markers in the bladder(12 months)