Summary

The enclosed abstract was presented at the 35th Annual Chemotherapy Foundation Symposium, New York. The abstract Hafnium oxide nanoparticles: an emergent promising treatment for solid tumors describes the story of hafnium oxide nanoparticles, NBTXR3, from the preclinical to the clinical development up to date.

Preclinical studies have demonstrated increase of cancer cells death in vitro and marked antitumor efficacy in vivo in presence of these nanoparticles (HfO2-NP) exposed to RT, when compared to RT alone. Hafnium oxide nanoparticles efficacy was assessed in cancer epithelial and mesenchymal tumor models and on patient-derived tumor xenografts in nude mice, showing superior anti-tumor effects, over radiation therapy alone in terms of complete response and overall survival. Additionally, in vivo cancer epithelial models in immunocompetent mouse have showed that HfO2-NP + RT triggers immunogenic conversion of the tumor microenvironment and generate an abscopal effect while this effect is not observed with RT alone.

HfO2-NP (NBTXR3), administered as a single intratumoral injection and activated by radiotherapy, is currently evaluated in clinical trials including soft tissue sarcoma (STS) [NCT02379845], head and neck [NCT01946867], prostate [NCT02805894], liver [NCT02721056; NCT02721056] and rectum cancers [NCT02465593]. Patients treated in phases I have had a good tolerance to the product and received radiotherapy as planned, confirming a very good local safety profile.

Besides, consistently with non-clinical studies, preliminary results of the phase II/III in patients with STS, beyond the expected cytotoxic effect induced by NBTXR3 + RT, suggest a release of tumor neoantigens during cancer cell death and stimulation of local immunological effects. This immunogenic cell death might convert “cold” tumor into “hot” tumor. Further analyses are ongoing to reinforce these findings.