Overview
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.
Eligibility
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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