Eftilagimod alfa is a soluble LAG-3 protein that improves antigen presentation by interacting with major histocompatibility complex class II (MHCII). Irene Brana, MD, Vall d’Hebron University Hospital and Institute of Oncology (VHIO), Barcelona, Spain, discusses the updated results of a Phase II trial (NCT03625323) investigating the efficacy of eftilagimod alfa and pembrolizumab in patients with PD-L1 unselected metastatic second-line squamous head and neck carcinoma. Eftilagimod alfa/pembrolizumab achieved a high overall response rate (ORR), almost double that of pembrolizumab found in the KEYNOTE-040 trial (NCT02252042); the highest response rate was found in patients with tumor proportion scores (TPSs) greater than 1. These promising findings will facilitate the trailing of eftilagimod alfa/pembrolizumab as a first-line treatment in metastatic squamous head and neck carcinoma and in patients with varying TPSs. This interview took place at the American Society of Clinical Oncology (ASCO) 2021 Virtual Meeting.