Targeted therapy could ultimately prove to be primary treatment for disease
AU-011 (Aura Biosciences) is a first-in-class drug being investigated as a treatment for choroidal melanoma with promising early results being reported from an ongoing phase Ib/II clinical trial, according to Amy Schefler, MD.
Dr. Schefler is an ocular oncologist in private practice, Retina Consultants of Houston, Houston, TX.
AU-011 is a bioconjugate combining recombinant viral-like particles (VLPs) derived from the human papillomavirus with a small molecule photosensitizer that is activated by 689-nm near infrared light (IR700DX).
Related: Targeted therapy for ocular melanoma
The VLPs bind selectively to uniquely modified heparan-sulfated proteoglycans that are overexpressed on the membrane of ocular melanoma cells. Laser irradiation with near-infrared light causes focused activation of the bioconjugate, leading to generation of reactive oxygen species that damage the melanoma cell membrane, causing acute tumor cell necrosis.
Damage to healthy surrounding tissue is avoided because of the dual specificity of the investigational agent’s mechanism of action, Dr. Schefler explained.
“Its dual specificity and ability to cause targeted necrosis likely confers a safety advantage for AU-011 compared with brachytherapy and explains the findings that are being observed in the clinical trial regarding change in tumor thickness and vision preservation,” she said.
Safety is being investigated as the primary objective of the phase Ib/II study, which has an ascending single and repeat dose design followed by two expansion cohorts. It initially enrolled patients with small to medium choroidal melanomas that met the clinical diagnosis agreed upon with the FDA and that would have been candidates for plaque brachytherapy.
Subsequently, patients with documented tumor growth and thinner tumors were enrolled to better evaluate the safety and efficacy in a broader range of tumor sizes with early stage disease, consisting of subjects with small choroidal melanoma or high-risk melanoma suspects.
In the current cohort, which is the last cohort being enrolled, there is a requirement for documented tumor growth within the past two years. Subjects in this cohort receive two cycles of treatment at an interval of three months. Each cycle consists of three weekly intravitreal injections of AU-011; each injection is followed by two laser light applications.
A total of 46 subjects have been treated in the phase Ib/II clinical trial. Safety data show that AU-011 has been well-tolerated in the majority of subjects.
In the overall population, the most common adverse events were anterior chamber inflammation, posterior chamber inflammation, and increased IOP, all of which are manageable with steroid and/or ocular anti-hypertensive therapy.