489P Analysis of 3-dimensional volumetric distribution and dispersion of the radioenhancer NBTXR3 in various solid malignancies

Abstract

NBTXR3, a first-in-class radioenhancer composed of functionalized hafnium oxide nanoparticles, is administered by one-time intratumoral (IT) injection and activated by radiotherapy (RT). It is designed to locally amplify the tumor-killing effect of RT without additional toxicity to surrounding healthy tissue. EU marketing approval was obtained in preoperative treatment of locally advanced soft tissue sarcomas (STS). Investigation in multiple tumor types is ongoing. Here we report feasibility and intra-tumor dispersion of IT NBTXR3 injection in patients with various solid malignancies: STS, head and neck squamous cell carcinoma (HNSCC), hepatocellular carcinoma (HCC), liver and lung metastases, pancreatic ductal adenocarcinoma (PDAC), esophageal cancer, and intra-prostate injection in patients with prostate adenocarcinoma. Patients with STS received NBTXR3+RT or RT alone followed by tumor resection in the phase II/III randomized Act.in.Sarc [NCT02379845] trial. NBTXR3 IT injection feasibility and safety is evaluated in phase I trials: HNSCC [NCT01946867], HCC or liver metastases [NCT02721056], advanced cancers in combination with anti-PD-1 [NCT03589339], PDAC [NCT04484909], esophageal cancer [NCT04615013], and prostate adenocarcinoma [NCT02805894]. IT injection in patients with STS, HNSCC, HCC, liver and lung metastases, PDAC, esophageal cancer, and intra-prostate injection is feasible. CT scan did not detect leakage in surrounding healthy tissues. IT dispersion ranged from 4.9-28.2% of tumor volume, depending on tumor size, with NBTXR3 treatment doses ranging from 5-22% in HNSCC, HCC, lung metastasis, STS, and prostate. Tumor responses were observed indicating the potential for NBTXR3 to improve patient outcomes at the doses tested and with dispersion within the tumor of up to 28.3%. Results from PDAC and esophageal cancer will be presented. IT injection of NBTXR3 is feasible in multiple tumor types and has shown favorable safety in several phase I studies. NBTXR3 demonstrated efficacy in a phase II/III study in patients with STS, and promising signs of efficacy have been observed in other tumor types.