A Phase 1b/2 Open-label Clinical Trial to Evaluate the Safety and Efficacy of AU-011 for the Treatment of Choroidal Melanoma

Abstract

Purpose : Choroidal melanoma (CM) is the most common primary ocular malignancy. Most small CMs are treated with radiotherapy which is associated with several adverse effects including vision loss. The safety and efficacy of AU-011, a novel targeted investigational therapy for the treatment of CM, is beingevaluated in an open-label, multi-center, dose escalation and expansion trial.

Methods : Subjects with a clinical diagnosis of CM with tumor thickness 1.2 - 3.4 mm and largest basal diameter ≤ 16 mm received intravitreal administration of a viral-like particle bioconjugate (AU-011) at doses of 20 µg, 40 µg, or 80µg followed by light-activation with a 689 nm laser at a fluence of 50 J/cm². Regimens consisting of 1, 2 or 3 weekly treatments with AU-011 each followed by 1 or 2 laser applications have been evaluated in 8 escalation cohorts and 1^stexpansion. Enrollment is ongoing in the 2^ndexpansion with subjects receiving two cycles of three weekly treatments with 80 µg /2 laser administrations separated by 12 weeks.

Results : 50 subjects have been treated in the trial. Interim results show local tumor control in 33/50 (66%) subjects (23/29 [79%] at therapeutic dose) and maintenance of visual acuity in 46/50 (92%) subjects (27/29 [93%] at therapeutic dose) with up to 24 months follow up. Linear regression was used to estimate tumor growth rates using tumor thickness measurements before and after treatment in subjects with historical documented growth (n=19). Tumor control was seen in 15/19 subjects and the post-treatment growth rate was significantly reduced compared to their historical growth rate (p=0.0056; paired t-test). There has been one treatment-related SAE of severe vision loss. Expected AEs related to treatment including intraocular inflammation and increased IOP were clinically manageable.

Conclusions : Interim results from this ongoing trial show preliminary safety and efficacy of AU-011. The therapy was well tolerated with maintenance of vision and tumor control in majority of subjects.AU-011 may offer an alternative to radiotherapy for treating small melanomas and high risk indeterminate lesions and further studies are planned to confirm the safety and efficacy.

This is a 2020 ARVO Annual Meeting abstract.