Avelumab plus cetuximab in patients with unresectable stage III or IV cutaneous squamous cell carcinoma: clinical activity and safety results from AliCe, a single-arm multicentre phase II DeCOG trial

BACKGROUND: In cutaneous squamous cell carcinoma (cSCC), programmed cell death protein 1 (PD-1) and epidermal growth factor receptor (EGFR) inhibitors are effective in a considerable proportion of patients. However, there is an unmet medical need for patients with perianogenital cSCC or cSCC refractory to PD-1 therapy. OBJECTIVES: To evaluate the combination avelumab (programmed death ligand 1 inhibitor) and cetuximab (EGFR inhibitor) in people with advanced cSCC treated for up to 1 year. METHODS: This multicentre phase II trial enrolled patients with advanced cSCC (prior systemic therapy allowed) to receive avelumab (10 mg kg-1 Q2W) plus cetuximab (500 mg m-2 Q2W) for up to 1 year. The primary endpoint was objective response. Predefined subgroups were line of therapy and localization of the primary tumour (perianogenital/other locations). RESULTS: Of 52 enrolled patients, 49 received at least 1 treatment dose. Of these patients, 20 achieved an objective response [41%, 95% confidence interval (CI) 27-56; 9 partial responses/11 complete responses (CRs)]. While treatment-naïve patients (n = 35) achieved a higher objective response rate (46%, 95% CI 29-63) than those who were pretreated (29%, 95% CI 8-58), 4 of 14 pretreated patients experienced an objective response, 2 with prior PD-1 inhibition. Five of 14 patients with perianogenital cSCC achieved an objective response (36%, 95% CI 13-65), including 4 CRs. At a median follow-up of 35 months, median progression-free and overall survival were 8.4 and 23.1 months, respectively. Grade 1 and 2 treatment-related adverse events (TRAEs) were common, while grade ≥ 3 events occurred in only 10 patients (20%) and 7 experienced serious TRAEs (14%); 2 discontinued treatment due to drug-related toxicity. Notably, quality of life improved, especially in patients with perianogenital primaries. CONCLUSIONS: Avelumab in combination with cetuximab demonstrates encouraging clinical activity in advanced cSCC, including patients with challenging subgroups such as perianogenital primaries or those with disease that has progressed on anti-PD-1 monotherapy. This is especially true when patients are carefully selected for their ability to undergo treatment for at least 12 weeks.