Avelumab + Cetuximab (PD‑L1 / EGFR) Halves Progression Risk vs Avelumab Alone in Advanced cSCC

Avelumab, an anti‑PD‑L1 IgG1, was paired with the EGFR antibody cetuximab in the Alliance A091802 randomized phase 2 trial (NCT03944941) enrolling 60 patients (57 evaluable) with unresectable or metastatic cutaneous SCC who were PD‑1/PD‑L1‑naïve. Over up to 2 years of treatment, median PFS improved to 11.1 mo (95% CI 7.6‑NR) with the doublet versus 3.0 mo (95% CI 2.7‑13.6) for avelumab alone (HR 0.48, p = .018); confirmed ORR was 27.6% vs 21.4%. Grade 3+ treatment‑related AEs rose to 48.3% with the combo (rash and infusion reactions each 20.7%) versus 21.5% for monotherapy. For context, single‑agent cemiplimab shows ORR ~44‑50% and median PFS ≈14‑18 mo in similar populations, while pembrolizumab reports ORR ~35% and median PFS ≈8 mo.