Bel-Sar Shows Promising Clinical and Immune Activity in NMIBC

Illustration of bladder cancer

A novel investigational therapy, belzupacap sarotalocan (bel-sar; AU-011), has demonstrated encouraging clinical and immune responses in patients with non–muscle-invasive bladder cancer (NMIBC), according to phase 1 data (NCT05483868) presented at the 40th Annual European Association of Urology (EAU) Congress in Madrid.¹

The window-of-opportunity trial evaluated bel-sar, a targeted therapy activated by light, in 15 patients with NMIBC. Ten patients received bel-sar plus light activation and 5 were given bel-sar alone.

Four out of 5 patients with intermediate-risk NMIBC treated with bel-sar and light achieved a clinical complete response, while 3 out of 5 high-risk patients showed visual tumor shrinkage on cystoscopy. Additionally, 57% of patients with multiple tumors exhibited complete responses in at least 1 non-target lesion, accompanied by infiltration of CD8+ and CD4+ T-cells, suggesting a systemic immune effect.

“The clinical complete responses 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,” said Sabine Brookman-May, MD, FEBU, senior vice president, therapeutic area head urologic oncology of Aura Biosciences, in the press release. “We look forward to our virtual urologic oncology investor event, where we will outline the phase 1b/2 trial to further evaluate bel-sar’s clinical activity and future development plans.”

Additional findings showed that no responses were observed among patients treated without light activation. Multiplex immunofluorescence in posttreatment biopsies in 3 patients revealed significant cytotoxic immune cell infiltration, de novo tertiary lymphoid structure formation in target and non-target lesions, and evidence of a bladder-wide urothelial field effect, which indicates potential immune surveillance beyond treated tumors.

For safety, bel-sar was well tolerated, with drug-related grade 1 adverse events (AEs) reported in less than 10% of patients. No grade 2 or higher drug-related AEs and no serious AEs were reported. There were also no significant differences between the light-activated and non-light activated cohorts observed.

“The positive data presented at EAU 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,” said Seth Lerner, MD, Scott Department of Urology, Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, in the press 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 Trial Design

The phase 1 window of opportunity trial is a 2-part, open-label study evaluating the safety and feasibility of bel-sar for the treatment of patients with NMIBC.² Enrollment is open to patients with a confirmed diagnosis of urothelial carcinoma of the bladder who have no evidence of metastatic disease. Patients must also have adequate bone marrow, renal, and hepatic function.

In the completed phase 1 window of opportunity trial, 5 patients received a single dose of bel-sar without light activation in part 1 and 10 patients with a confirmed tumor at time of treatment received either 100 ug or 200 ug of bel-sar as a single dose in part 2.

Incidence and severity of treatment-related AEs and serious AEs and incidence of dose-limiting toxicities served as the primary end points of the study. Secondary end points include distribution of bel-sar, area of necrosis of bladder tumor, and degree of necrosis of bladder tumor.

Of the 10 patients enrolled in this portion of the study, 5 patients had intermediate-risk disease and 5 had high-risk disease at the time of treatment. Eight patients had a history of recurrent bladder cancer and had undergone multiple TURBTs and adjuvant treatments like Bacillus Calmette-Guerin, mitomycin, gemcitabine, cetrelimab, and tamoxifen prior to trial enrollment.¹

References

1. 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, Inc. March 24, 2025. Accessed March 25, 2025. https://tinyurl.com/2dw8jz98

2. A phase 1, open-label trial of belzupacap sarotalocan (AU-011) in bladder cancer. ClinicalTrials.gov. Updated June 12, 2024. Accessed March 25, 2025. https://clinicaltrials.gov/study/NCT05483868