Metronomic carboplatin/paclitaxel + PD-1 blocker cemiplimab delivers 42.5% ORR (15% CR) in 1L R/M HNSCC, with cytokine shifts tied to outcome

Cemiplimab is an anti–PD-1 monoclonal antibody combined here with metronomic weekly carboplatin (AUC1) and paclitaxel (25 mg/m²) to potentially retain chemo–immune priming with less toxicity than standard-dose regimens. In a single-arm Phase II trial (NCT04862650) in first-line recurrent/metastatic HNSCC, 40 evaluable patients (35% HPV-positive) achieved ORR 42.5% with 15% CR and median OS 14.8 months (95% CI, 10.3–23.9) at 10-month median follow-up; as a benchmark, KEYNOTE-048 reported median OS 13.0 months with pembrolizumab + platinum/5-FU in the total population (and ~10.7 months with cetuximab + platinum/5-FU), with best results in PD-L1 CPS≥20 (14.7 months). Cytokine profiling (baseline, week 3, week 6) linked higher IFN-β to response (P=.008–.04), baseline IL-4/IL-5/IL-10 to improved ORR, and early rises in IFN-γ and IL-4Rα (baseline→week 3) to worse OS (HR 3.23, P=.006; HR 3.06, P=.008); notably, safety/tolerability outcomes were not reported in this abstract, which is a central question given the “metronomic = better tolerated” premise.