A Phase 1/1b Study of ZH9 Treatment in Patients With Non-Muscle Invasive Bladder Cancer

NCT06181266 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: PRK-23101
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 4

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.

Conditions

NMIBC; High Risk NMIBC; Non Muscle Invasive Bladder Cancer

Outcome Measures

Primary Outcomes (1)

• Incidence of dose-limiting toxicities

  Toxicity will be evaluated according to the NCI CTCAE Version 5.0

  28 days

Secondary Outcomes (7)

• Rate of complete pathologic response

  3, 6, and 12 months

• Rate of recurrence-free survival and duration or response

  3, 6, and 12 months

• Rate of CR

  6 and 12 months

• Proportion of patients with cystectomy-free survival

  6 and 12 months

• Rate of progression-free survival

  12 months

Study Arms (4)

Dose Level 1 - ZH9

EXPERIMENTAL

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

Drug: ZH9

Dose Level 2 - ZH9

EXPERIMENTAL

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

Drug: ZH9

Dose Level 3 - ZH9

EXPERIMENTAL

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

Drug: ZH9

Dose Level 4 - ZH9

EXPERIMENTAL

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

Drug: ZH9

Interventions

ZH9 DRUG

ZH9 is a live attenuated S. enterica serovar Typhi ZH9 \[Ty2 ΔaroC ΔssaV\]), a differentiated novel microbial immunotherapy.

Dose Level 1 - ZH9; Dose Level 2 - ZH9; Dose Level 3 - ZH9; Dose Level 4 - ZH9

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Prokarium Ltd: lead

Study Sites (4)

Michael G. Oefelein Clinical Trials

Bakersfield, California, 93301, United States

Location

Duke Health-Duke Cancer Center

Durham, North Carolina, 27710, United States

Location

Carolina Urologic Research Center, LLC

Myrtle Beach, South Carolina, 29572, United States

Location

Urology San Antonio Medical Center

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Non-Muscle Invasive Bladder Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urinary Bladder Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Josefin-Beate Holz, MD

  Prokarium Ltd

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: 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).
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: December 12, 2023
• First Posted: December 26, 2023
• Study Start: January 8, 2024
• Primary Completion: August 30, 2025
• Study Completion (Estimated): July 30, 2027
• Last Updated: August 19, 2025

Record last verified: 2025-08

Locations

US (4)