Bel-Sar Shows Tolerability and Preliminary Antitumor Activity in NMIBC

Bel-Sar in NMIBC | Image Credit:

© Sebastian Kaulitzki – stock.adobe.com

Belzupacap sarotalocan (AU-011; bel-sar), an investigational virus-like–drug conjugate, demonstrated a tolerable safety profile and preliminary signs of biologic activity in patients with non–muscle-invasive bladder cancer (NMIBC), according to results from a phase 1 window-of-opportunity study (NCT05483868) presented at the 40th Annual European Association of Urology (EAU) Congress.1,2

Among patients in the light-activated cohort (n = 10), 4 of 5 patients with intermediate-risk NMIBC achieved a clinical complete response (CR), defined as the absence of tumor cells on histopathological evaluation, and 3 had necrosis.2 Among the 5 patients with high-risk disease, 1 achieved a clinical CR, and 3 experienced visible tumor shrinkage on cystoscopy. Furthermore, 57% of evaluable patients (n = 4/7) with multifocal disease in this cohort experienced a clinical CR in at least 1 non-target lesion.

All patients (n = 5) who received bel-sar without light activation had intermediate-risk NMIBC; in this group, no patients had a clinical CR, and tumor shrinkage was not reported.

Multiplex immunofluorescence staining from biopsies obtained post-treatment in 3 patients revealed significant infiltration of CD4- and CD8-positive T cells, and the presence of tertiary lymphoid structures in both target and non-target lesions. Additionally, de novo formation of mature tertiary lymphoid structures (TLS) occurred in 2 of these 3 patients following treatment, and early TLS were observed in distant, non-target lesions.

Bel-sar was well-tolerated; grade 1 treatment-related adverse effects (TRAEs) were reported in less than 10% of patients. No grade 2 or higher TRAEs and no serious AEs were reported. No significant differences between the light-activated and non–light-activated cohorts were observed.

“The positive data presented at [the] EAU [Congress] are compelling and suggest that bel-sar has the potential to introduce a new front-line focal treatment approach instead of or ahead of transurethral resection of bladder tumor [TURBT] in patients across different risk categories,” presenting study author Seth Lerner, MD, of the Scott Department of Urology at Dan L. Duncan Comprehensive Cancer Center of Baylor College of Medicine in Houston, Texas, stated in a news release. “With its favorable safety profile and the ability to be administered without general anesthesia, this novel modality could expand treatment options for patients and may represent a shift in how we approach NMIBC management.”

Phase 1 Study Design

The phase 1 window-of-opportunity trial was an open-label, 2-part clinical study designed to evaluate the safety, feasibility, and preliminary biological activity of bel-sar in patients with NMIBC. The trial was conducted in patients scheduled to undergo TURBT, the standard of care in this population, and assessed the intravesical administration of bel-sar prior to surgery.

A total of 15 patients were enrolled across 2 study parts. In part 1 (n = 5), patients received a single dose of bel-sar without subsequent light activation. Part 2 enrolled 10 patients who received either 100 µg or 200 µg of bel-sar administered as a single intravesical dose. Among these 10 patients, 5 had intermediate-risk NMIBC, and 5 had high-risk disease. Eight of the 10 patients had a history of recurrent bladder cancer with prior treatments that included multiple TURBT procedures, Bacillus Calmette–Guérin (BCG), mitomycin, gemcitabine, cetrelimab, and tamoxifen.

Bel-sar was administered 7 to 12 days prior to the scheduled TURBT, enabling the evaluation of bel-sar's biologic effects in the pre-surgical setting. Patients were followed for safety monitoring over a 56-day period post-treatment.

The primary objective of the trial was to assess safety and feasibility of bel-sar. Histopathologic evaluation of tumor tissue collected during TURBT was a secondary end point.

“The clinical CRs and the immune responses seen with a single low dose of bel-sar in such a short time frame are highly encouraging. This reinforces our belief that this novel mechanism of action could be the key to generating long term durable responses,” Sabine Brookman-May, MD, FEBU, senior vice president, therapeutic area head of Urologic Oncology at Aura Biosciences, stated in a news release.

References

1. Kates M, Brookman-May SD, McQuaid J, et al. Safety and efficacy of Bel-sar (AU-011), a Virus-like-Drug-Conjugate (VDC) in patients with Non-Muscle Invasive Bladder Cancer (NMIBC). Presented at: 40th Annual European Association of Urology Congress; March 21-24, 2025; Madrid, Spain. Abstract LB15.
2. Positive data from phase 1 trial of bel-sar in patients with non–muscle-invasive bladder cancer (NMIBC) presented at the 40th Annual European Association of Urology Congress. News release. Aura Biosciences. March 24, 2025. Accessed April 4, 2025. https://ir.aurabiosciences.com/news-releases/news-release-details/positive-data-phase-1-trial-bel-sar-patients-non-muscle-invasive