Phase 2 cemiplimab PD-1 inhibitor ± fianlimab LAG-3 antibody with induction chemo for NPC.

This Memorial Sloan Kettering–sponsored pilot randomized trial tests whether adding immune checkpoint blockade to induction therapy can maintain control while enabling de-escalated definitive chemoradiation in locoregionally advanced, non-metastatic nasopharyngeal carcinoma. Patients are randomized to induction cemiplimab (Regeneron/Sanofi; an anti–PD-1 monoclonal antibody that reinvigorates exhausted T cells) versus cemiplimab + fianlimab (Regeneron; an anti–LAG-3 monoclonal antibody intended to deepen T-cell activation by blocking a second inhibitory checkpoint), given alongside gemcitabine (a nucleoside analog that impairs DNA synthesis) and cisplatin (a DNA–crosslinking platinum). After induction, participants receive a reduced-intensity chemoradiation strategy, aiming to preserve cure rates while potentially lowering long-term toxicity (swallowing dysfunction, xerostomia, hearing loss). Today’s care for fit patients with locoregionally advanced NPC is induction gemcitabine/cisplatin followed by definitive concurrent chemoradiation (typically cisplatin-based), with growing global interest in bringing PD-1–based regimens earlier—this study’s angle is whether dual-checkpoint (PD-1 + LAG-3) can justify safely dialing back chemoradiation intensity.