ASCO GU 2023: A Phase 1, Open-Label Trial to Evaluate Feasibility and Safety of Intramural Injection of Belzupacap Sarotalocan (AU-011) in Non-Muscle–invasive Bladder Cancer (NMIBC)

(UroToday.com) On the second day of the American Society for Clinical Oncology (ASCO) Genitourinary Cancer Symposium 2023 focussing on urothelial cancer, the Trials in Progress Poster Session B included a presentation from Dr. Seth Lerner presented the design of the phase I AU-011 trial assessing the feasibility and safety of intramural injection of belzupacap sarotalocan in non-muscle–invasive bladder cancer (NMIBC).

There is a large unmet clinical need for bladder sparing therapies in patients with NMIBC, in order to avoid subsequent development of recurrence and progression leading, ultimately, cystectomy. One novel treatment paradigm involves celzupacap sarotalocan, a novel investigational virus-like drug conjugate (VDC), which has a dual mechanism of action designed to provide both selective binding to malignant cells, causing acute necrosis upon light activation, and long-term anti-tumor immunity as demonstrated in pre-clinical models.

In this Phase 1 trial (NCT05483868), the authors aim to evaluate the feasibility and safety of intramural injection with or without intratumoral injection of belzupacap sarotalocan for treatment of NMIBC, testing the hypothesis that, after near infrared light activation, targeted distribution of belzupacap sarotalocan at high concentrations at the tumor base could necrose the tumor where it is most likely to be invasive. The authors hypothesize that such a tumor targeted pro-immunogenic cell death could potentially lead to an anti-tumor immune response decreasing the risk for recurrence, progression and metastasis.

To test this hypothesis, they are performing an actively enrolling “window of opportunity” trial in low, medium or high risk NMIBC subjects scheduled to undergo TURBT or cystectomy per standard of care. A pre-treatment biopsy will be performed in up to 23 adult subjects enrolled in 4 cohorts, who will be given belzupacap sarotalocan +/- laser.

The primary endpoint is incidence and severity of treatment-related adverse events, serious adverse events regardless of attribution, and incidence of dose-limiting toxicities. Each cohort will have a safety review for the injection procedure and laser (as needed), after 3 subjects have been treated and followed for 28 days. Beyond the primary safety and feasibility endpoints, secondary endpoints are based on histopathology and include assessment of local biodistribution of belzupacap sarotalocan measured via immunohistochemical staining, tumor necrosis, and evidence of an immune response via comparison of pre-treatment biopsy to TURBT/cystectomy samples after treatment. These endpoints will be assessed in a descriptive fashion.