NBTXR3 (hafnium oxide radioenhancer) + SBRT reirradiation followed by anti–PD-1 drives 48% ORR in recurrent/metastatic HNSCC

NBTXR3 is an intratumoral hafnium oxide nanoparticle “radioenhancer” designed to locally amplify radiation effects and potentially augment immune priming; in Study 1100 (Phase I dose escalation/expansion; NCT03589339), patients with previously irradiated recurrent (R) or recurrent+metastatic (R+M) HNSCC received NBTXR3 injection (22% or 33% of gross tumor volume), SBRT 35Gy/5 fractions, then nivolumab or pembrolizumab (30 treated; 27 efficacy-evaluable; 16 ICI-naïve and 14 ICI-resistant; 55% HPV-negative). Grade ≥3 events included 13.3% injection-related, 26.7% RT-related, and 20% NBTXR3-related toxicities; notably, carotid injury was not observed, while injection-site pain (10%) and soft tissue necrosis (6.7%) were among the more frequent injection/NBTXR3-related AEs. Across all disease sites (injected + non-injected), ORR was 48.1% (13/27) and DCR 77.8% (21/27); outcomes separated sharply by pattern of disease—R only: ORR 64.7% (11/17), DCR 88.2% vs R+M: ORR 20% (2/10), DCR 60%—and these response rates look well above anti–PD-1 monotherapy benchmarks in platinum-refractory R/M HNSCC (ORR ~13%–16% in CheckMate 141 nivolumab and KEYNOTE-040 pembrolizumab), though cross-trial comparison is confounded by the addition of SBRT and different eligibility.