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

Prokarium

Status and phase: Enrolling; Phase 1

Conditions: NMIBC; High Risk NMIBC; Non Muscle Invasive Bladder Cancer

Treatments: Drug: ZH9

Study type: Interventional

Funder types: Industry

Identifiers

NCT06181266

PRK-23101

Details and patient eligibility

About

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.

Enrollment: 24 estimated patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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24 participants in 4 patient groups

Dose Level 1 - ZH9

Experimental group

Description:

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

Treatment:

Drug: ZH9

Dose Level 2 - ZH9

Experimental group

Description:

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

Treatment:

Drug: ZH9

Dose Level 3 - ZH9

Experimental group

Description:

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

Treatment:

Drug: ZH9

Dose Level 4 - ZH9

Experimental group

Description:

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

Treatment:

Drug: ZH9