Reirradiation with NBTXR3/SBRT in combination with nivolumab or pembrolizumab for the treatment of patients with recurrent or metastatic head & neck squamous cell carcinoma (HNSCC) in the phase I trial study 1100.

6034 Background: HNSCC reirradiation with stereotactic body radiation therapy (SBRT) has emerged as a potential option for the management of locoregionally recurrent (R) or metastatic (M) HNSCC, however treatment toxicity remains a limiting factor. NBTXR3 is a novel intratumoral radioenhancer composed of functionalized hafnium oxide nanoparticles which locally amplifies radiation therapy (RT). In pre-clinical models, NBTXR3/RT has demonstrated an ability to generate cell killing effects at low RT doses as well as trigger local and systemic immune responses. Here we report outcomes in pts with R or R+M HNSCC who were treated with reirradiation with NBTXR3/SBRT followed by immune checkpoint inhibitors (ICIs). Methods: A phase I dose escalation/expansion trial [NCT03589339] evaluating NBTXR3/SBRT followed by ICI (nivolumab or pembrolizumab) included a subgroup with R or R+M HNSCC that were either naïve or resistant to prior ICI. Pts received an intra-tumoral NBTXR3 injection at dose of 22% or 33% of gross tumor volume (GTV), SBRT (35 Gy in 5 fractions), and ICI. Primary objective was safety and establishing RP2D of NBTXR3/SBRT/anti-PD-1 combination. The expansion part tested the RP2D (33% of GTV). Secondary objectives include efficacy. Results: From June 2019 to February 2025, 30 pts were treated: 16 ICI naïve, 14 ICI resistant with median age of 67 years, 90% ECOG 0-1, and 55% HPV negative. 20 pts (66.7%) had R disease, 10 (33.3%) pts had R+M disease. All injected lesions were in a previously irradiated H&N field. Median time from end of prior radiotherapy to NBTXR3 injection was 21.3 [5-229] months. Median GTV was 16.1 [3-110] mL. 4 pts (13.3%) experienced G≥3 injection-related AEs, 8 (26.7%) G≥3 RT-related AEs, and 6 (20%) G≥3 NBTXR3-related AEs. Carotid injury was not observed. Most frequent injection or NBTXR3-related AEs were injection site pain (10%), oropharyngeal pain (6.7%), tumor pain (6.7%), dysphagia (6.7%), and soft tissue necrosis (6.7%). 27 pts (90%) were evaluable for efficacy. For all disease (i.e. injected and non-injected), the objective response rate (ORR) was 48.1% (13/27) and disease control rate (DCR) was 77.8% (21/27). In R pts, ORR was 64.7% (11/17) and DCR was 88.2% (15/17). In R+M pts, ORR was 20% (2/10) and DCR was 60% (6/10). Survival outcomes in reirradiation pts with R and R+M HNSCC will be presented. Conclusions: Reirradiation with NBTXR3 with SBRT and anti-PD1 was feasible in R or R+M HNSCC with an adverse effect profile expected for this clinical setting. Encouraging preliminary efficacy outcomes have been observed, thus warranting further investigation. Clinical trial information: NCT03589339 .