Low-dose bel-sar shows promising safety, efficacy in NMIBC in phase 1 study

Single, low-dose belzupacap sarotalocan (bel-sar; AU-011) demonstrated encouraging clinical activity with a favorable safety profile in patients with non–muscle-invasive bladder cancer (NMIBC), according to initial data from an ongoing phase 1 trial (NCT05483868).¹

The company plans to expand the phase 1 trial to further evaluate the optimal dose and treatment regimen.

According to a news release from Aura Biosciences, the developer of the therapy, “Bel-sar is a virus-like particle conjugated to a light-activatable drug payload and is designed to have a dual mechanism of action, inducing direct tumor cell necrosis and pro-immunogenic cell death that elicits a robust and durable anti-tumor immune response.”

The agent was granted a fast track designation by the FDA in July 2022.²

The open-label, phase 1 trial of bel-sar is structured in 2 parts. In part 1, 5 patients with low-grade NMIBC were treated with single dose bel-sar without light activation.

Part 2 of the study is ongoing, with 8 of 10 patients having been treated at the time of data cutoff. Of these, 5 patients had low-grade disease, and 3 patients had high-grade disease. Each participant in this portion of the trial received bel-sar with light activation, injected either intratumorally or intramurally at the dose level of either 100 µg or 200 µg. Of the 8 patients enrolled in the cohort, 7 had a history of recurrent cancer and had undergone multiple transurethral resections of bladder tumor (TURBTs) and prior adjuvant treatments.

Bel-sar was administered to all patients 7 to 14 days prior to TURBTs.

Overall, 4 of 5 patients with low-grade disease who received bel-sar with light activation achieved a complete clinical response, defined as no tumor cells detected on histopathological evaluation post-treatment. Immune activation was observed in all treated tumors, as well as all untreated tumors. According to Aura Biosciences, this finding provides “evidence of a bladder urothelial field effect with a single low dose of bel-sar.”¹

Regarding safety, no grade 2/3 adverse events (AEs) and no serious AEs have been reported. Less than 10% of patients have experienced a grade 1 AE. There were no significant differences in the safety profiles of patients who received bel-sar with vs without light activation.

An analysis of changes to the tumor microenvironment post-treatment showed a significant infiltration of effector CD8+ and CD4+ T cells in the target tumors of patients who received bel-sar with light activation, with detection as early as 7 days. T cell infiltration was also seen in non-target tumors of the 5 patients who had available biopsies at the time of data cutoff.

“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. 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,” said Neal Shore, MD, FACS, U.S. Chief Medical Officer of Surgery and Oncology at GenesisCare, in the news release.¹ “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.”

In total, the phase 1 trial plans to include 21 patients with NMIBC. Enrollment for the study is taking place across clinical trial sites in the United States. To be eligible for enrollment, 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.³

According to Aura Biosciences, the company plans to expand the phase 1 trial to further evaluate the optimal dose and treatment regimen. They also plan to “prepare a Phase 2 trial that could potentially be expanded to support registration.”

References

1. Multiple clinical complete responses demonstrated following single low dose administration of bel-sar in patients with non-muscle-invasive bladder cancer (NMIBC) in ongoing phase 1 trial. News release. AURA Biosciences. October 17, 2024. Accessed October 18, 2024. https://ir.aurabiosciences.com/news-releases/news-release-details/multiple-clinical-complete-responses-demonstrated-following

2. Aura Biosciences receives FDA fast track designation for belzupacap sarotalocan (AU-011) for the treatment of non-muscle invasive bladder cancer. News release. Aura Biosciences. June 30, 2022. Accessed October 17, 2024. https://bwnews.pr/3yAoEPt

3. A Phase 1, open-label trial of belzupacap sarotalocan (AU-011) in bladder cancer. ClinicalTrials.gov. Last updated June 12, 2024. Accessed October 17, 2024. https://clinicaltrials.gov/study/NCT05483868