{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T05:00:00Z","timestamp":1781067600829,"version":"3.54.1"},"reference-count":17,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>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\u2013Friday 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.<\/jats:p>","DOI":"10.3389\/fonc.2026.1797703","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T04:29:48Z","timestamp":1781065788000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Pilot study of topical imiquimod combined with pembrolizumab for unresectable cutaneous metastatic melanoma"],"prefix":"10.3389","volume":"16","author":[{"given":"Joseph B.","family":"Parker","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Mayo Clinic Florida","place":["Jacksonville, FL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard W.","family":"Joseph","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Mayo Clinic Florida","place":["Jacksonville, FL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera J.","family":"Suman","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences, Mayo Clinic","place":["Rochester, MN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyi","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Mayo Clinic Florida","place":["Jacksonville, FL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruqin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Mayo Clinic Florida","place":["Jacksonville, FL, United 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