Multinational phase 1 trial of intratumoral radioenhancer nanoparticle NBTXR3 followed by radiotherapy in head and neck cancer

A phase 1 dose-expansion nonrandomized clinical trial at 20 centers in Europe evaluated intratumoral delivery of the radioenhancer nanoparticle NBTXR3 followed by radiotherapy (RT) for locally advanced head and neck squamous cell carcinoma (LA HNSCC) in cisplatin-ineligible and cetuximab-ineligible patients. The trial included 56 patients with unresectable T3-4 or overall stage III/IVA HNSCC (median age 72 years; range 44-89; 71% men; 61% aged 79 years or older; 64% with age-adjusted Charlson Comorbidity Index score of 4 or greater). Patients received a single intratumoral admistration of NBTXR3 in the primary tumor followed by RT (70 Gy over 35 fractions). NBTXR3-related treatment-emergent adverse events occurred in 9 patients (16%), of which 11% were grade 3 or higher. Objective tumor response was assessed in 44 patients. In this population, the objective response rate of the primary tumor was 82% (95% CI 67-92) and the ORR of all lesions was 80% (65-90). Among all 56 patients, the median progression-free survival was 11.4 months (95% CI 6.7-NR) and the median overall survival was 18.1 months (9.7-NR). The authors conclude that these findings suggest that intratumoral NBTXR3 followed by RT in a high-risk patient population unable to receive cisplatin or cetuximab was feasible and had a preliminary efficacy signal that supports a benefit-risk profile being evaluated in a randomized phase 3 trial.