Authors
Christophe Le Tourneau1, Victor Moreno Garcia2, Bernard Doger2, Andrzej Urban3, Katell Bernois3, Xavier Liem4, Sébastien Salas5, Stéphanie Wong5, Nicolas Fakhry5, Mikaela Dimitriu3, Valentin Calugaru1, Caroline Hoffmann1
1 – Institut Curie, Paris, France
2 – START Madrid, Madrid, Spain
3 – Nanobiotix, SA ; Paris, France
4 – Centre Oscar Lambret, Lille, France
5 – Hôpital Timone, APHM, Marseille, France
Summary
Introduction: New therapeutic approaches are needed for elderly or frail head and neck squamous cell carcinoma (HNSCC) patients (pts) ineligible for standard of care. NBTXR3, hafnium oxide nanoparticles injected intratumorally, may represent an option. Otherwise inert, NBTXR3 augments the radiation therapy (RT) dose within tumor cells when activated by RT, increasing tumor cell death compared to RT alone.
Objectives: The purpose of this Phase I was to evaluate safety (dose limiting toxicity; DLT) and determine the NBTXR3 recommended phase 2 dose (RP2D) in elderly or frail HNSCC pts.
Methods: Eligible pts had stage III or IV HNSCC of oral cavity or oropharynx, were aged ≥70 years or ≥65 years and unable to receive cisplatin but eligible for RT [NCT01946867]. A 3+3 dose escalation design was employed, with NBTRX3 dose levels of 5%, 10%, 15% and 22% of baseline tumor volume. Following intratumoral NBTXR3 injection, pts received IMRT (70 Gy; 35 fractions/7 weeks). Primary endpoints were RP2D and DLT. Localization of NBTXR3 and preliminary efficacy (RECIST 1.1) were also evaluated.
Results and Conclusion: Dose escalation is complete; 19 pts received NBTXR3: 3 at 5%, 3 at 10%, 5 at 15% and 8 at 22%. No NBTXR3-related DLTs or SAEs were observed. Four related AEs were reported: one AE at 15% (G1 tumor hemorrhage) and 3 AEs at 22% (G2 oral pain; G1 asthenia, G1 injection site hemorrhage). IMRT toxicity was as expected and post-injection CT scan showed NBTXR3 localized within the injected tumor. DSMB determined RP2D to be 22%. Among 13 evaluable pts at doses ≥10%, 9 had a complete response of injected tumor. Results demonstrate that NBTXR3 activated by RT is a well-tolerated therapy with encouraging anti-tumor activity. RP2D expansion is ongoing. NBTXR3 may be an option for elderly or frail pts with locally advanced HNSCC.
