Bel-Sar Generates Tumor Control, Preserves Visual Acuity in Early Choroidal Melanoma

First-line treatment with bel-sar (AU-011) led to tumor control and preservation of visual acuity in patients with early-stage choroidal melanoma, according to end-of-study data from a phase 2 trial (NCT04417530) announced by Aura Biosciences and presented at the 2024 Retina Society Annual Meeting.

Findings showed that phase 3–eligible patients (n = 10) treated with the investigative agent achieved a tumor control rate of 80%. Complete cessation of growth following treatment was also observed with a post-treatment average growth rate of 0.011 mm per year among responders compared with 0.351 mm per year prior to study entry (P < .0001).

Furthermore, visual acuity preservation was achieved in 90% of patients treated. In this population, 80% of patients were at high risk for vision loss with tumors close to the fovea or optic disc.

“Many patients with early-stage choroidal melanoma currently face the difficult choice of whether to treat the cancer and risk losing their vision in the treated eye, or delay treatment and risk the tumor progressing,” Ivana K. Kim, MD, stated in a news release. “Bel-sar has the potential to become the first treatment that achieves the dual goals of treating the tumor while also preserving vision, which could change the treatment paradigm for patients with this disease.”

Kim is the Evangelos S. Gragoudas Chair in Ophthalmology, director of the Macular Degeneration Unit, and director of the Ocular Melanoma Center at Massachusetts Eye and Ear, and an associate professor of Ophthalmology at Harvard Medical School, both located in Boston.

Radiotherapy is the current standard of care for patients who present with choroidal melanoma, which can lead to visual acuity of worse than 20/200—the cutoff for legal blindness—in the treated eye in up to 87% of patients. Due to the typically poor prognosis associated with choroidal melanoma, Aura Biosciences noted that these phase 2 results are a significant achievement, particularly because there are no currently approved vision-preserving therapies.

The open-label, ascending, single and repeat dose-escalation trial evaluated the safety, tolerability, and efficacy of bel-sar in patients with early-stage choroidal melanoma, defined as small choroidal melanoma and indeterminate lesions. Furthermore, a total of 22 patients were enrolled onto the trial between the single and multiple ascending-dose cohorts. Upon enrollment, eligible patients were monitored over a 12-month follow-up period to assess tumor control, visual acuity preservation, and tumor growth rate.

Safety data for bel-sar was favorable in all patients, regardless of dose. No treatment-related serious adverse effects (AEs) were reported. Ocular treatment-related AEs (TRAEs) were mild (grade 1), including anterior chamber inflammation (18%) or cell (9%), and both were resolved without sequelae. Approximately 70% of these anterior chamber inflammation/cell events were self-limited, required no treatment, and resolved in a median of 6 days. In patients where these TRAEs required treatment, topical steroid eye drops were administered for a median of 6 days and achieved complete resolution of the inflammation.

Additionally, 9% of patients experienced mild grade 1 eye pain. However, no treatment-related posterior inflammation AEs, including vitritis, choroiditis, retinitis, retinal pigment epithelium changes, or vasculitis, were reported.

“We believe these phase 2 results provide clinical evidence for bel-sar as a potential vision-sparing, first-line treatment option for patients with early-stage choroidal melanoma,” Jill Hopkins, MD, chief medical officer and president of Research and Development at Aura Biosciences, added in the news release. “Bel-sar is potentially a first-in-class novel therapy and we are excited to continue to advance this program, which is currently enrolling patients in our ongoing global phase 3 CoMpass trial [NCT06007690].”

Notably, Aura Biosciences reached an agreement with the FDA through a Special Protocol Assessment for the design and proposed analysis of the global phase 3 CoMpass trial. If successful, the study will be sufficient to meet the objectives required to support Aura’s planned submission of a biologics license application for bel-sar.

Reference

Aura Biosciences reports positive phase 2 end of study results evaluating bel-sar as a first-line treatment for early-stage choroidal melanoma. Aura Biosciences. September 12, 2024. Accessed September 12, 2024. https://ir.aurabiosciences.com/news-releases/news-release-details/aura-biosciences-reports-positive-phase-2-end-study-results