This record contains raw data related to article "Immunotherapy followed by cetuximab in locally advanced/metastatic cutaneous squamous cell carcinomas: the I-TACKLE trial" Abstract Background: Immunotherapy with pembrolizumab and cemiplimab achieves an overall response rate (ORR) of 34-51 % in locally advanced/metastatic (LA/M) cSCC, but primary and acquired resistance remains a challenge. This study evaluates whether adding cetuximab to pembrolizumab can overcome resistance by reducing immune escape. Patients and methods: I-TACKLE is a phase II, open-label trial conducted at three Italian centers. Patients received intravenous pembrolizumab 200 mg every 3 weeks, and cetuximab was added in cases of stable disease or progression. The primary endpoint was cumulative ORR by a single agent or by combination strategy. Secondary endpoints included safety, progression-free survival (PFS), overall survival (OS), and response duration. Results: From May 2019 to April 2021, 43 patients were enrolled and treated with pembrolizumab, and 23 received combination therapy. Median treatment durations were 3 months (pembrolizumab) and 4 months (combination). Cumulative ORR was 63 % [95 % CI 48-77], with 19/43 (44 %) responding to pembrolizumab and 8/21 (38 %) responding to the combination after resistance. Both patients experiencing an acquired resistance to pembrolizumab obtained partial response when cetuximab was introduced. Overall, 10/23 (44 %) responded to the combination. One-year PFS was 51 % with pembrolizumab and 42 % with combination therapy. Grade 3-4 treatment-related adverse events occurred in 7/43 (16 %) during pembrolizumab and 8/23 (35 %) during combination therapy, primarily dermatitis (30 %). Conclusions: In LA/M cSCC, the addition of cetuximab to pembrolizumab reverts primary and acquired resistance with manageable toxicities. This sequential approach warrants further study. Keywords: Cetuximab; Cutaneous squamous cell carcinoma; Pembrolizumab; Resistance to immune-checkpoint inhibitors.