Bi-specific antibodies are an emerging frontier in HNSCC therapy, with MCLA-158 (petosemtamab) demonstrating a preliminary ORR of approximately 30% inR/M HNSCC by targeting EGFR and LGR5, surpassing the 23.5% ORR in CheckMate 651 (see above) and 17–18% in EAGLE (see above) (Table 2) [114,115]. This evidence concerns the gene EGFR and head and neck squamous cell carcinoma.