842P A phase II trial of AU-011, an investigational, virus-like drug conjugate (VDC) for the treatment of primary indeterminate lesions and small choroidal melanoma (IL/CM) using suprachoroidal administration

Abstract

Choroidal melanoma is the most common primary intraocular malignancy in adults. Many subjects with a melanocytic choroidal tumor of indeterminate malignancy (i.e., ‘indeterminate lesion’) or small choroidal melanoma (IL/CM) are monitored clinically or treated with radiotherapy, which may lead to severe and irreversible vision loss. AU-011 (belzupacap sarotalocan) is a virus-like drug conjugate (VDC) currently being investigated as a potential first-line vision-sparing treatment. The dual mechanism of action consists of AU-011 selectively binding to malignant melanoma cells, causing acute necrosis upon light activation and potential long term anti-tumor immunity. The current Phase 2 trial is designed to evaluate the safety and efficacy of AU-011 when administered via suprachoroidal (SC) injection. Trial design using SC administration and interim safety from the open-label dose escalation phase will be presented. Phase 2, multicenter trial being conducted at 22 ocular oncology sites in the US. The trial included 6 single- and multiple-dose escalation cohorts to be followed by a randomized confirmatory phase. In dose escalation, adult subjects received up to 3 cycles of 3 weekly AU-011 treatments via SC administration with a maximum dose of 80μg with 2 laser applications. Preliminary safety results include 17 subjects in the dose escalation phase. The most common adverse events (AE) related to drug or laser were anterior chamber inflammation in 4 subjects, conjunctival hyperemia, eye pain, and punctate keratitis in 2 subjects each. There were no dose-limiting toxicities, treatment-related serious or grade 3/4 AEs, vitritis or serious AEs of vision loss. Two subjects developed 5 serious AEs unrelated to treatment. Preliminary results indicate AU-011 to have a favorable safety profile, supporting its potential to be a first-line therapy for the treatment of IL/CM, especially in early-stage disease where observation may be commonly employed. Efficacy data including visual acuity and tumor control from the dose escalation phase will be reported later this year.