Bel-Sar Elicits Complete Responses in NMIBC

Neal Shore, MD, FACS

A single, low dose of belzupacap sarotalocan (bel-sar; AU-011) generated complete responses (CRs) in patients with low-grade non–muscle-invasive bladder cancer (NMIBC), according to interim results from a phase 1 trial (NCT05483868) announced by Aura Biosciences.¹

Findings showed that among 5 patients with low-grade NMIBC treated with bel-sar without light activation in part 1 of the study, 4 achieved a clinical CR with no tumor cells detected in a post-treatment histopathological evaluation in the target and several non-target tumors.

Across the 2 parts of the study, 13 patients with NMIBC have been treated with bel-sar, including 8 additional patients who received bel-sar with light activation in part 2 of the study. Notably, 5 patients enrolled in part 2 had low-grade NMIBC, and 3 had high-grade disease. Following a single dose of bel-sar, clinical activity was observed in the form of tumor shrinkage, immune activation, and histopathological evidence of cancer cell absence or necrosis.

“We are highly encouraged by this positive early data, which shows that bel-sar has the potential to be a transformative cancer treatment,” Sabine Brookman-May, MD, FEBU, senior vice president and therapeutic area head of Urologic Oncology at Aura Biosciences, stated in a news release. “A potentially differentiating aspect of this novel treatment is the rapid tumor response accompanied by an immuno-oncology [IO] effect such as a marked CD8+ T-cell infiltration observed in just a matter of days with a single low dose. We believe this could have the potential to translate into a durable response. In parallel with expanding the ongoing phase 1 trial, we are preparing for a phase 2 trial to further evaluate bel-sar’s clinical activity and durability of response.”

Bel-sar is a virus-like drug conjugate. The agent features a dual mechanism of action intended to induce direct tumor cell necrosis and generate a robust and durable antitumor immune response.

The ongoing phase 1 study is enrolling patients at least 18 years of age with a confirmed diagnosis urothelial carcinoma of the bladder.² Patients need to have recurrence of prior NMIBC confirmed by biopsy or pathology within 12 months of enrollment, or newly diagnosed NMIBC via biopsy within 6 months of screening. Patients with MIBC are allowed to enroll if the malignancy is confirmed pathologically. Other key inclusion criteria consist of no evidence of metastatic disease, and adequate bone marrow, renal, and hepatic function.

Patients are being excluded if they received an investigational drug or medical device within 30 days or 5 half-lives of the first visit; are concurrently enrolled in another investigational trial; have active bacterial, fungal, or viral infections; or have chronic, active hepatitis B/C or HIV.

In part 1 of the study, which has been completed, patients with low-grade NMIBC received a single dose of bel-sar without light activation.¹ In part 2, patients are receiving bel-sar with light activation, and this part of the trial is investigating 2 injection methods and 2 dose levels of bel-sar (100 µg and 200 µg). Across both parts, bel-sar is being administered 7 to 12 days prior to standard-of-care transurethral resection of bladder tumor (TURBT).

The incidence of dose-limiting toxicities and serious adverse effects (AEs) is serving as the trial’s primary end point.²

Among the 8 patients treated thus far in part 2, 7 had a history of recurrent NMIBC and underwent multiple TURBTs and adjuvant therapies, including BCG, mitomycin, gemcitabine, cetrelimab, and tamoxifen before enrollment.¹

Regarding safety, bel-sar was well-tolerated; grade 1 treatment-emergent AEs related to the agent occurred in less than 10% of patients, and no patients had grade 2 or higher AEs related to bel-sar. No patients experienced serious AEs. Notably, safety data were consistent irrespective of the use of light activation.

“Bel-sar has the potential to change the treatment paradigm for NMIBC. Based on this early data, bel-sar’s positive clinical activity and evidence of a bladder urothelial field effect with a single dose, may position bel-sar to be the first immune ablative treatment option for early-stage bladder cancer patients delivered with an in-office procedure,” Neal Shore, MD, FACS, United States chief medical officer of Surgery and Oncology at GenesisCare, added in the news release.

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 17, 2024. https://www.globenewswire.com/news-release/2024/10/17/2965223/0/en/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-T.html
2. A phase 1, open-label trial of belzupacap sarotalocan (AU-011) in bladder cancer. ClinicalTrials.gov. Updated June 12, 2024. Accessed October 17, 2024. https://www.clinicaltrials.gov/study/NCT05483868