988 An open-label phase 2 clinical trial of topical remetinostat gel for basal cell carcinoma

Abstract

There is a great need for non-surgical therapies for patients with frequent basal cell cancers (BCCs) as the repeated surgeries can lead to severe morbidity and functional impairment. We conducted a systematic computational drug repositioning screen which identified histone deacetylase (HDAC) inhibitors as a potential therapy for BCC. We showed that HDAC inhibitors can suppress Hedgehog signaling and growth of BCC cells and murine BCC allografts, though optimal therapeutic effect was limited by systemic toxicity. Here, we report interim results of an open-label clinical trial of the topical HDAC inhibitor, remetinostat, as a neoadjuvant treatment for BCC. Remetinostat is designed to be metabolically labile so that topical application produces effective local HDAC inhibition in tumors while minimizing systemic HDAC inhibition and toxicity. Enrolled subjects had at least 1 BCC of any subtype between 5 and 25mm in size. Participants applied remetinostat gel 1% 3 times/day under bandage occlusion to BCC(s) for 6 weeks prior to undergoing surgical excision. The primary outcome was overall response rate (ORR) measured by at least a 30 percent decrease in BCC greatest diameter. Secondary objectives include suppression of Gli1 mRNA expression and the safety and tolerability of remetinostat. This trial has enrolled 11 patients with 27 BCCs, ranging in baseline size from 6-25 mm greatest diameter, with enrollment goal of 30 tumors. Among the 8 BCCs that completed the trial, the ORR was 75%. The longest diameter of BCCs shrank by an average of 73%, and tumor area lowered by an average of 81%. 50% (4) of tumors achieved complete clinical resolution. Grade 2 eczematous local site reactions occurred in 100% (8) tumors treated with topical remetinostat. No systemic toxicities have been observed. In conclusion, initial results suggest that remetinostat gel offers a potentially effective, non-surgical intervention for treatment of localized BCCs. We will report updated trial results in May.