Clinical trial NCT06181266: A Phase 1/1b Study of ZH9 Treatment in Patients With Non-Muscle Invasive Bladder Cancer
Official title: A Phase 1/1b Study Evaluating the Safety, Pharmacology, and Clinical Effect of ZH9 Treatment in Patients With Non-Muscle Invasive Bladder Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: NMIBC
High Risk NMIBC
Non Muscle Invasive Bladder Cancer
Lead sponsor: Prokarium Ltd
Sponsor class: INDUSTRY
First posted: 2023-12-26
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Incidence of dose-limiting toxicities
timeFrame: 28 days
Secondary outcomes:
measure: Rate of complete pathologic response
timeFrame: 3, 6, and 12 months
measure: Rate of recurrence-free survival and duration or response
timeFrame: 3, 6, and 12 months
measure: Rate of CR
timeFrame: 6 and 12 months
measure: Proportion of patients with cystectomy-free survival
timeFrame: 6 and 12 months
measure: Rate of progression-free survival
timeFrame: 12 months
measure: Overall response rate and recurrence-free rate
timeFrame: 6 and 12 months
measure: Change from baseline in systemic and local inflammatory markers in the bladder
timeFrame: 12 months
Other outcomes:
Locations:
city: Bakersfield
country: United States
facility: Michael G. Oefelein Clinical Trials
state: California
city: Durham
country: United States
facility: Duke Health-Duke Cancer Center
state: North Carolina
city: Myrtle Beach
country: United States
facility: Carolina Urologic Research Center, LLC
state: South Carolina
city: San Antonio
country: United States
facility: Urology San Antonio Medical Center
state: Texas
Study officials:
affiliation: Prokarium Ltd
name: Josefin-Beate Holz, MD
role: STUDY_DIRECTOR
References: