High Risk NMIBC, NMIBC, Non Muscle Invasive Bladder Cancer
Conditions
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.
Interventions
DRUGZH9
ZH9 is a live attenuated S. enterica serovar Typhi ZH9 \[Ty2 ΔaroC ΔssaV\]), a differentiated novel microbial immunotherapy.
Sponsors
Prokarium Ltd
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
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).
Intervention model description
In Part 1, the safety, tolerability, and pharmacology of ZH9 administered as an IVI will be evaluated in a single ascending dose cohort in patients with NMIBC. Part 1 may examine up to 4 dose levels. In Part 2, the safety, tolerability, and pharmacology of ZH9 oral prime followed by ZH9 IVI will be evaluated in 2 cohorts in patients with NMIBC at the doses and schedule established in Part 1. In Part 3, the safety, pharmacology, and clinical efficacy of ZH9 (oral prime and IVI) will be further evaluated in 2 expansion cohorts of patients with recurrent intermediate- and high-risk NMIBC.
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of dose-limiting toxicities | 28 days | Toxicity will be evaluated according to the NCI CTCAE Version 5.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 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 |
| 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) |
| Rate of progression-free survival | 12 months | Rate of progression-free survival, including disease progression and all-cause death |
Countries
United States
Outcome results
None listed