Study launches exploring immunotherapy regimen in NMIBC

The first patient has been dosed in the PARADIGM-1 phase 1/1b clinical trial (NCT06181266) assessing the investigational immunotherapy ZH9 in patients with non–muscle-invasive bladder cancer (NMIBC), announced Prokarium, the developer of the therapy, in a news release.¹

Primary completion of the study is expected in the first quarter of 2025.

ZH9 is a proprietary bacterial immunotherapy administered to patients via a single-dose intravesical induction regimen. The first-in-human, double-blind, multicenter PARADIGM-1 study will assess the safety, tolerability, and pharmacology of the therapy in patients with NMIBC.²

“We are excited to have dosed our first patient in Prokarium’s PARADIGM-1 study. The trial provides us the opportunity to explore an innovative treatment approach for our NMIBC patients who are facing significant gaps in available effective treatment options,” said Daniel Zainfeld, MD, in the news release.¹ Zainfeld is a urologic oncologist at Urology San Antonio in Texas.

The study is enrolling patients across multiple clinical sites throughout the US and is being conducted with a 3-part design.

Part 1 of the study will assess the safety, tolerability, and pharmacology of ZH9 in a single ascending dose cohort. Up to 4 dose levels may be assessed in this phase of the study, which will be conducted in a standard 3+3 escalation design. Patients will receive ZH9 via intravesical induction (IVI).

Part 2 of the study will randomly assign patients 1:1 to receive either ZH9 or placebo oral prime followed by ZH9 IVI to further assess the safety, tolerability, and pharmacology of the therapy in patients with NMIBC. Patients will receive ZH9 at the dose level and schedule determined in part 1 of the study.

Part 3 of the study will assess the safety, pharmacology, and clinical efficacy of the ZH9 oral prime and IVI treatment regimen in patients with recurrent intermediate- or high-risk NMIBC. This phase of the study will include 2 dose expansion cohorts.

The primary end point for the study is the incidence of dose-limiting toxicities according to NCI CTCAE version 5.0 within 28 days of therapy administration. Secondary outcome measures include the complete pathologic response rate, the complete response rate, recurrence-free survival and duration of response, and progression-free survival.

Primary completion of the study is expected in the first quarter of 2025.

ZH9 is a part of Prokarium’s larger immunotherapy platform called Living Cures, which was granted an investigational new drug (IND) application acceptance by the FDA in November 2023.³ The IND includes explorations of the ZH9 treatment regimen in the dose expansion cohorts.

Kristen Albright, CEO of Prokarium, concluded in the news release, "We are grateful to the patients and urologists involved in the PARADIGM-1 clinical trial. This achievement represents a pivotal moment for Prokarium as we introduce Living Cures, a novel class of immunotherapies built with synthetic biology.”¹

References

1. Prokarium achieves milestone with first patient dosing in PARADIGM-1 non-muscle invasive bladder cancer clinical trial. News release. Prokarium. February 7, 2024. Accessed February 8, 2024. https://www.businesswire.com/news/home/20240207504370/en/

2. A Phase 1/​1b study of ZH9 treatment in patients with non-muscle invasive bladder cancer (PARADIGM-1). ClinicalTrials.gov. Last updated January 19, 2024. Accessed February 8, 2024. https://clinicaltrials.gov/study/NCT06181266

3. Prokarium achieves major milestone with FDA’s IND approval for bladder cancer program. News release. Prokarium. November 2, 2023. Accessed February 8, 2024. https://www.businesswire.com/news/home/20231102543739/en/Prokarium-Achieves-Major-Milestone-with-FDAs-IND-Approval-for-Bladder-Cancer-Program