Ficerafusp alfa (EGFR×TGF-β trap) + pembrolizumab drives deeper shrinkage and ~10-mo mPFS in 1L HPV− R/M HNSCC

Ficerafusp alfa (BCA101) is a bifunctional EGFR-directed antibody engineered to trap TGF-β, combined here with pembrolizumab (anti–PD-1) in two Phase 1/1b first-line dose-expansion cohorts for PD-L1 CPS≥1, HPV-negative recurrent/metastatic HNSCC (NCT04429542). Among efficacy-evaluable patients (750mg n=30; 1500mg n=28), confirmed ORR was similar (57% vs 54%) but the 1500mg cohort showed more “deep” responses (≥80% shrinkage in 80% vs 47% of responders), longer median DOR (21.7mo vs NR), and longer mPFS (9.9mo vs 6.9mo), with mOS 21.3mo (NR at 750mg); paired biopsies/blood also showed dose-related pharmacodynamic shifts consistent with stronger TGF-β pathway inhibition and immune activation (e.g., pSMAD2 −33.2% vs −16.4%). Versus pembrolizumab monotherapy in KEYNOTE-048 for CPS≥1 disease (ORR ~19% and mOS 12.3mo) and pembrolizumab+chemo (mOS benefit vs EXTREME in CPS≥1), this single-arm Phase 1/1b dataset looks efficacy-competitive on response depth/durability—though cross-trial comparisons and selection effects are major caveats.