Pilot study of topical imiquimod combined with pembrolizumab for unresectable cutaneous metastatic melanoma.

Cutaneous metastases occur in up to 20% of patients with advanced melanoma and can be difficult to manage with systemic therapy alone. Pembrolizumab is a standard therapy with limited local treatment options for cutaneous manifestations. Imiquimod has shown activity in other skin cancers but is less well studied in melanoma. We conducted a pilot trial to evaluate the feasibility, safety, and preliminary efficacy of combining topical imiquimod with intravenous pembrolizumab in patients with unresectable melanoma with cutaneous metastases. This was a single-center, open-label, non-randomized interventional study (NCT03276832). Eligible patients received pembrolizumab IV every 21 days plus topical imiquimod 5% applied Monday-Friday each cycle. The primary endpoint was objective response rate per RECIST v1.1. Secondary endpoints included progression-free survival, and safety. In this study, seven patients were enrolled, five were male and two females; one was Hispanic and six were non-Hispanic White. Median treatment exposure was 8 cycles. ORR was 57.1%, with 3 patients (42.9%) achieving complete response, 1 partial response, and 2 stable disease. The 7-month PFS rate was 57.1%. At study closure, 4 patients remained alive without progression, 2 were alive following progression, and 1 had died of disease. Toxicities were mostly grade 1, with fatigue and anemia most common with minimal grade 2 events. The combination of topical imiquimod and pembrolizumab was feasible, safe, and demonstrated promising antitumor activity in unresectable cutaneous melanoma. A 42.9% CR rate in this small elderly cohort supports further evaluation of local immune modulation with systemic PD-1 blockade for cutaneous melanoma.