Early signs of efficacy in patients with anti-PD-1 naïve and anti-PD-1 resistant HNSCC treated with NBTXR3/SBRT in combination with nivolumab or pembrolizumab in the phase I trial Study 1100.

6035 Background: Overcoming resistance to immune checkpoint inhibitors (ICIs) is a major clinical challenge. NBTXR3, a novel radioenhancer composed of functionalized hafnium oxide nanoparticles administered by a single intratumoral injection, locally amplifies radiotherapy (RT) dose without adding toxicity to surrounding healthy tissue. NBTXR3/RT enhances tumor cell death, tumor antigen release, and effectively expands T-cell repertoire in preclinical models, thus potentially triggering local and systemic immune responses to help improve ICI treatment. NBTXR3 has demonstrated favorable local control in pts with LA-HNSCC. Here we report early outcomes from the ongoing Study 1100 trial in pts with locoregionally recurrent (LRR) or metastatic (M+) head lung 45 Gy/ 5 fxns; liver 45 Gy/ 3 fxns; soft tissue as per investigator. Primary objective is safety of NBTXR3/RT/anti-PD-1 combination and its RP2D. Secondary objectives include efficacy. Results: The RP2D was 33%. There were 55 pts with HNSCC treated in the dose escalation/expansion parts. NBTXR3 injection was feasible and safe. There were 11pts (20%) who experienced G≥3 treatment related AEs, of which 3 pts experienced G≥3 AEs (5.5%) related to NBTXR3. Preliminary results of 33 pts, who were evaluable for efficacy: are reported. 6 pts with LRR disease: (2 ICI resistant, 4 naïve);. 27 pts with M+ disease (18 ICI resistant, 9 naïve). In ICI-resistant pts, objective tumor responses were observed in 25% (5/20), and the disease control rate (DCR) was 75% (15/20). In the ICI-naïve population, objective tumor responses were observed in 54% (7/13) of pts and DCR was 77% (10/13). There were observed improvements in injected lesions as well as in some noninjected target lesions. Updated efficacy data including OS in resistant and naïve pts will be presented. Conclusions: NBTXR3/RT/anti-PD-1 combination was feasible and well tolerated. Early data suggest the addition of NBTXR3/RT to ICI showed evidence of efficacy, including in patients who failed prior ICI, opening up an opportunity to further explore the ability of NBTXR3/RT to mitigate primary or secondary resistance to ICI. Clinical trial information: NCT03589339 .