Ficerafusp alfa (EGFR/TGF‑β) + Pembrolizumab Achieves 64% ORR in HPV‑Negative R/M HNSCC

In a Phase 1/1b expansion (N=42; 39 evaluable), the combination yielded a 54% ORR overall and 64% in HPV‑negative patients—with 21% achieving complete response—with durable responses (≥ 6 months in 72% overall and 73% in HPV‑negative patients). The median PFS was 7.4 months overall and 9.8 months in HPV‑negative participants. In HPV‑negative patients, the mOS exceeded the data cutoff of 20 months. Safety was consistent with known profiles, and pSMAD2 downregulation confirmed TGF‑β inhibition. These findings support advancing the combination into the FORTIFI‑HN01 phase 2/3 trial for first‑line PD‑L1‑positive, HPV‑negative R/M HNSCC.