BCA101 (EGFR/TGF‑β bifunctional antibody) + pembrolizumab drives 54% ORR in 1L HPV− R/M HNSCC

Ficerafusp alfa (BCA101) is a bifunctional EGFR-targeting antibody fused to a TGF‑β “trap,” designed to counter EGFR-driven signaling and TGF‑β–mediated immune exclusion; it was combined with pembrolizumab (anti–PD-1) as first-line therapy in a Phase I/Ib expansion cohort (NCT04429542) enrolling PD‑L1 CPS≥1 R/M HNSCC (n=42 treated; 39 efficacy-evaluable; median follow-up 26.3 months). Grade 3 TRAEs occurred in 45% and grade 4 TRAEs in 2%, with the most common grade ≥3 events anemia (14%) and acneiform dermatitis (12%). Confirmed ORR was 54% in HPV− disease (CR 21%; n=28) and 27% in HPV+ disease (n=11); in HPV− tumors, median DOR was 21.7 months, median PFS 9.9 months, and median OS 21.3 months—numerically above pembrolizumab monotherapy benchmarks in PD‑L1 CPS≥1 R/M HNSCC (ORR ~19%, mPFS ~3.2 months, mOS ~12.3 months in KEYNOTE‑048), though cross-trial comparisons are inherently noisy and this is a small, nonrandomized cohort.