EGFR-directed bispecific + PD-1 blockade

This combination pairs an EGFR-directed bispecific antibody, petosemtamab or ficerafusp alfa, with the PD-1 inhibitor pembrolizumab in head and neck squamous cell carcinoma. EGFR blockade with ADCC-competent antibodies induces immunogenic cell death and, in the case of ficerafusp, also removes TGF-beta-mediated immune exclusion; PD-1 blockade then sustains the resulting T-cell response. In phase 2 single-arm studies, petosemtamab with pembrolizumab produced a response rate far above that expected with immunotherapy alone, and ficerafusp alfa with pembrolizumab produced durable responses in HPV-negative disease. Both pairings are now in registrational phase 3 trials, LiGeR-HN1 and FORTIFI-HN01, so the evidence remains uncontrolled for the moment.