Belzupacap sarotalocan (bel-sar; AU-011), a novel therapy developed by Aura Biosciences, has shown promising early results in patients with non-muscle-invasive bladder cancer (NMIBC). Initial data from an ongoing phase 1 trial (NCT05483868) indicate encouraging clinical activity and a favorable safety profile following single, low-dose administration of the drug.
The open-label, phase 1 trial is being conducted in two parts. The first part involved five patients with low-grade NMIBC who received a single dose of bel-sar without light activation. The second part is ongoing and includes ten patients, eight of whom have been treated at the time of data cutoff. Among these, five had low-grade disease and three had high-grade disease. Participants in the second part received bel-sar with light activation, administered either intratumorally or intramurally at doses of 100 µg or 200 µg. Notably, seven of the eight patients in this cohort had a history of recurrent cancer and had undergone multiple transurethral resections of bladder tumor (TURBTs) and prior adjuvant treatments.
Clinical Response and Immune Activation
Bel-sar was administered 7 to 14 days before TURBTs. Results showed that 4 of 5 patients with low-grade disease who received bel-sar with light activation achieved a complete clinical response, defined as the absence of tumor cells on histopathological evaluation post-treatment. Furthermore, immune activation was observed in all treated tumors, as well as in untreated tumors. Aura Biosciences suggests that this finding provides evidence of a bladder urothelial field effect with a single low dose of bel-sar.
Safety Profile
The safety profile of bel-sar has been favorable, with no grade 2/3 adverse events (AEs) or serious AEs reported. Less than 10% of patients experienced a grade 1 AE. The safety profiles were similar between patients who received bel-sar with and without light activation.
Mechanism of Action and T Cell Infiltration
Bel-sar is designed with a dual mechanism of action, inducing direct tumor cell necrosis and pro-immunogenic cell death, which elicits a robust and durable anti-tumor immune response. Post-treatment analysis of the tumor microenvironment revealed significant infiltration of effector CD8+ and CD4+ T cells in the target tumors of patients who received bel-sar with light activation, detectable as early as 7 days. T cell infiltration was also observed in non-target tumors of the five patients with available biopsies at the data cutoff.
Expert Commentary
"Bladder cancer patients are faced with limited treatment options and a shortage of BCG. A large proportion of patients endure persistent recurrences, leading to multiple surgeries and adjuvant treatments over time, considerably impacting their quality of life," said Neal Shore, MD, FACS, U.S. Chief Medical Officer of Surgery and Oncology at GenesisCare. "Bel-sar’s immune ablative mechanism of action may offer patients an effective, minimally invasive treatment option with a favorable safety profile that may prevent recurrence of the disease and preserve the bladder function. This novel therapy with a focal delivery is administered as an in-office procedure without the need for general anesthesia, representing an opportunity to provide a less invasive option for patients. With the potential to obviate the need for multiple surgeries, bel-sar could completely change the treatment paradigm in this disease."
Trial Expansion and Future Plans
The phase 1 trial plans to enroll a total of 21 patients with NMIBC across clinical trial sites in the United States. To be eligible, patients must have a confirmed diagnosis of urothelial carcinoma of the bladder, no evidence of metastatic disease, and adequate bone marrow, renal, and hepatic function. Aura Biosciences intends to expand the phase 1 trial to further evaluate the optimal dose and treatment regimen and prepare for a phase 2 trial that could potentially support registration. The agent was granted fast track designation by the FDA in July 2022.
