The light-activated agent AU-011 continues to show promise in early trials of its use in choroidal melanoma, said Carol L. Shields, MD, speaking on Friday during the “Late-Breaking Developments, Part 1” session (Ret10V) at Retina Subspecialty Day.
Mechanism of action. AU-011 (Aura Biosciences) is a viral-like nanoparticle that is conjugated to infrared-activated small molecules. The nanoparticles are modeled on the human papillomavirus (HPV) and bind specifically to heparin-sulfated proteoglycans expressed by ocular melanoma cells. After being activated by an ophthalmic laser, the nanoparticles disrupt the tumor cell membrane, leading to acute cellular necrosis and a secondary antitumor immune response, Dr. Shields said. Healthy surrounding tissue is unharmed.
Method of delivery. AU-011 can be delivered by either intravitreal or suprachoroidal injection.
Study 1: Intravitreal delivery. In a phase 1b/2 trial, 57 patients with a clinical diagnosis of choroidal melanoma were enrolled; to date, 56 have been treated, Dr. Shields said. Four single-dose cohorts, four multiple-dose cohorts, and two dose-expansion cohorts have been completed, she noted.
- Safety profile. “This is a fairly safe medication,” Dr. Shields said. “Overall, the most common side effects include inflammation—of the anterior chamber in about 70% of cases and of the vitreous in about 86% of cases.” Increased intraocular pressure (IOP) also was observed in 41% of cases. Following treatment, the majority of the adverse events resolved without clinical sequelae, she said.
- Impact on vision. Vision was preserved in 91% of the patients, with visual acuity results staying relatively “flat,” Dr. Shields said. “People really don’t lose vision with this medication.”
- Tumor control. All told, tumor control was evident in 55% of patients at a mean of 15 months of follow-up, Dr. Shields said. However, this includes those whom Dr. Shields described as “underdosed”—that is, they received the lowest dose of the drug. In contrast, 80% of those who underwent two cycles with the highest dose showed tumor control at a mean of eight months of follow-up.
Study 2: Suprachoroidal administration. This method of delivery should lower the incidence of intraocular inflammation, and it has the potential to increase the number of treatable patients, Dr. Shields said.
A phase 2 study was initiated in August, and enrollment is anticipated to be completed in January 2021. To date, three single-dose cohorts have completed treatment, and the researchers are proceeding with two multiple-dose cohorts. The safety profile is favorable at this time.
Looking ahead. AU-011 has the potential to be the first targeted therapy for the treatment of small choroidal melanomas and indeterminate lesions, Dr. Shields said. And in response to positive feedback in the chat box, she wrote, “This is the first new thing in ocular oncology [in] 50 years!” —Jean Shaw
Watch the Retina Subspecialty Day. If you are registered for AAO 2020 Virtual, you have access to the archived presentations on the virtual meeting platform until Feb. 15, 2021. Log in to the virtual meeting platform: Next, from the Lobby screen, select “Sessions” from the top navigation; click “Agenda” from the drop-down menu; and click on the “Friday” tab.
Financial disclosures. Dr. Shields: Aura Biosciences: C; Immunocore: C.
Disclosure key. C = Consultant/Advisor; E = Employee; L = Speakers bureau; O = Equity owner; P = Patents/Royalty; S = Grant support.
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