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.
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
