Topical remetinostat gel is well-tolerated and can reduce tumor burden in patients with basal cell carcinoma (BCC), according to results of a phase 2 trial published in Clinical Cancer Research.

To develop novel treatments for BCC, researchers previously conducted an in silico drug repositioning screen using molecular data from human BCCs. The screen revealed histone deacetylase (HDAC) inhibitors as a potential treatment option. Subsequent preclinical studies showed that HDAC inhibitors could inhibit the growth of BCC cell lines and allografts. 

Remetinostat is an inhibitor of several HDAC isoforms (HDAC 1, 3, and 6) that was designed to “retain potency within the skin but be rapidly metabolized upon absorption, thus producing effective local activity in cutaneous lesions with negligible systemic effects,” the researchers noted.

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They tested topical remetinostat gel in a first-in-human, phase 2 trial of patients with BCC ( Identifier: NCT03180528).

The study included 25 patients with 33 tumors in the per-protocol analysis. All patients applied 1% remetinostat gel 3 times daily for 6 weeks. Tumor diameter was measured at baseline and week 8.

Remetinostat yielded an overall response rate (ORR) of 69.7%, including 6 partial and 17 complete responses. The average change in the longest tumor diameter was a 62.3% decrease. None of the tumors increased in size.

Remetinostat was most effective against the superficial subtype of BCC. The ORR was 100% for the superficial (n=6), 68.2% for the nodular (n=22), 66.7% for the infiltrative (n=3), and 0% for the micronodular (n=2) subtype.

Pathologic examination showed complete histologic resolution of BCC in 17 tumors (54.8%), while 14 (45.2%) had microscopic residual tumor.

Analysis of drug penetration and pharmacologic activity in pre- and post-treatment biopsies showed similar levels of acetylated histone H3 in the skin tissue. However, phosphorylation increased after treatment.

The most common adverse event (AE) was an eczematous reaction that occurred at the site of drug application. There were 27 of these AEs in all — 5 grade 1, 21 grade 2, and 1 grade 3.

There were no serious or systemic AEs reported during treatment or follow-up.

“Given the tolerability and clinical and pathologic response rates demonstrated in this trial across several histological subtypes, HDAC inhibitors could be a realistic new class of topical agents for BCC,” the researchers wrote. “In patients suffering from recurrent disease, an effective topical treatment could have a revolutionary impact on patient outcomes, morbidity, and quality of life.”

Disclosures: This research was partly supported by Medivir AB. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Kilgour JM, Shah A, Urman NM, et al. Phase II open-label, single-arm trial to investigate the efficacy and safety of topical remetinostat gel in patients with basal cell carcinoma. Clin Cancer Res. Published online August 6, 2021. doi: 10.1158/1078-0432.CCR-21-0560