A Phase 1/1b Study of ZH9 Treatment in Patients With Non-Muscle Invasive Bladder Cancer
- Conditions
- Non Muscle Invasive Bladder CancerNMIBCHigh Risk NMIBC
- Interventions
- Registration Number
- NCT06181266
- Lead Sponsor
- Prokarium Ltd
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 24
- 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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Dose Level 1 - ZH9 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 Dose Level 2 - ZH9 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 Dose Level 3 - ZH9 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 Dose Level 4 - ZH9 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
- Primary Outcome Measures
Name Time Method Incidence of dose-limiting toxicities 28 days Toxicity will be evaluated according to the NCI CTCAE Version 5.0
- Secondary Outcome Measures
Name Time Method Rate of complete pathologic response 3, 6, and 12 months Rate of complete pathologic response at determined timepoints by cystoscopy, urine cytology, and if needed for pathological confirmation, biopsy
Rate of recurrence-free survival and duration or response 3, 6, and 12 months Rate of recurrence-free survival and duration of response as determined by cystoscopy and urine cytology
Rate of CR 6 and 12 months Rate of CR as determined by biopsy in patients with CIS at baseline
Proportion of patients with cystectomy-free survival 6 and 12 months Proportion of patients with cystectomy-free survival as determined by cystoscopy and urine cytology
Rate of progression-free survival 12 months Rate of progression-free survival, including disease progression and all-cause death
Overall response rate and recurrence-free rate 6 and 12 months Overall response rate and recurrence-free rate in the bladder following IVI
Change from baseline in systemic and local inflammatory markers in the bladder 12 months Change from baseline in systemic and local inflammatory markers in the bladder as defined by clinical laboratory safety assessments (serum chemistry, hematology, urinalysis)
Trial Locations
- Locations (4)
Michael G. Oefelein Clinical Trials
🇺🇸Bakersfield, California, United States
Duke Health-Duke Cancer Center
🇺🇸Durham, North Carolina, United States
Carolina Urologic Research Center, LLC
🇺🇸Myrtle Beach, South Carolina, United States
Urology San Antonio Medical Center
🇺🇸San Antonio, Texas, United States