468 Is topical remetinostat gel an effective and safe treatment for basal cell carcinoma? Results of a phase 2, open label, single arm trial

Abstract

Surgical excision remains the gold standard treatment for basal cell carcinoma (BCC). However, it is associated with potential morbidity, particularly for patients with multiple or recurrent tumors. To identify novel treatment option for BCC, we previously used molecular data from human BCCs to conduct a drug repositioning screen. Our results identified histone deacetylase (HDAC) inhibitors as the leading predicted therapeutic, strongly opposing the BCC gene-expression signature. We conducted a phase 2, open label, single arm and institution trial of the topical pan-HDAC inhibitor, remetinostat, as the first proof-of-principle study of this medication class for BCC. Participants with at least one BCC referred for excision at Stanford were recruited and instructed to apply 1% remetinostat gel three times daily for six weeks. Measurements of tumor diameter and photography were conducted at baseline and week 8, and remaining tumor was then excised for histological examination, with a subset also sent for immunohistochemistry (IHC). 25 participants with 33 BCCs were included in the per-protocol analysis. The objective response rate (the proportion of tumors achieving at least a 30% decrease in the longest diameter from baseline to week 8) was 69.7% (90% confidence interval 54-82.5%), and 54.8% of the tumors demonstrated complete resolution on histological examination. IHC staining supported the pharmacodynamic effect of the remetinostat, demonstrating increased acetylated histone H3 in the excised biopsies compared to baseline. No systemic adverse events were reported, and the medication was well tolerated. Remetinostat, a topical pan-HDAC inhibitor, is a safe and effective topical treatment for BCC, reducing disease burden in a clinically significant manner. Our results provide the first in-human validation of HDAC inhibitors as a potential therapeutic.