NBTXR3, a new therapeutic option for elderly/frail HNSCC patients

ASCO, Chicago · 2019, C. Le Tourneau et al.


Christophe Le Tourneau1, Victor Moreno Garcia2, Sébastien Salas3, Xavier Mirabel4, Emiliano Calvo2, Bernard Doger2, Carmen Florescu5, Juliette Thariat5, Jacek Fijuth6, Tomasz Rutkowski7 Nicolas Magné8, Xavier Liem4, Nicolas Fakhry3, Stéphanie Wong3, Valentin Calugaru1, Caroline Hoffmann1

1 – Institut Curie, Paris, France
2 – START Madrid, Madrid, Spain
3 – Hôpital Timone, APHM, Marseille, France
4 – Centre Oscar Lambret, Lille, France
5 – Unicancer – François Baclesse Center, Caen, France
6 – Provita Prolife, Tomaszów Mazowiecki, Poland
7 – Maria Skłodowska-Curie Institute of Oncology, Gliwice, Poland
8 – Institut de Cancérologie Lucien Neuwirth, Saint-Priest-en-Jarez, France


Background: New therapeutic approaches are needed for elderly or frail head and neck squamous cell carcinoma (HNSCC) patients (pts) ineligible for standard of care treatment. NBTXR3, a crystalline solution of hafnium oxide nanoparticles may represent such an option. Injected intratumorally, NBTXR3 enters tumor cells and yields an increased cell-localized energy deposit upon exposure to radiotherapy (RT), leading to increased tumor cell death compared to the same dose of RT alone.

Methods: Phase I study of NBTXR3 activated by RT in pts ≥70 years old or ≥65 years old and unable to receive cisplatin, eligible for exclusive RT with stage III or IV HNSCC of the oral cavity or oropharynx [NCT01946867]. A 3+3 dose escalation design was implemented with dose levels corresponding to 5%, 10%, 15% and 22% of baseline tumor volume, followed by an expansion phase. Pts received an intratumoral (IT) injection of NBTXR3 and intensity modulated RT (IMRT; 70 Gy/35fractions/7 weeks). Determination of Recommended Phase 2 Dose (RP2D) and Dose Limiting Toxicities (DLT) were primary endpoints of phase I. Absence of NBTXR3 leakage and preliminary efficacy using RECIST 1.1 principles were also evaluated.

Results: The doseescalation is complete. Nineteen pts were enrolled: 3 at 5%, 3 at 10%; 5 at 15% and 8 at 22% with no observed DLT or SAE related to NBTXR3 or IT injection. One grade 1 NBTXR3-related AE (asthenia at 22%) and four IT injection-related AE (grade 2 oral pain; grade 1 tumor hemorrhage; grade 1 asthenia, and grade 1 injection site hemorrhage) were reported. RT-related toxicity was as expected with IMRT. RP2D has been determined to be 22%. CTscan assessment between 24h and 7 weeks post-IT injection demonstrated absence of NBTXR3 leakage in the surrounding tissues. Among 13 evaluable pts treated at doses ≥10%, 9 achieved a complete response of the injected lesion.

Conclusions: These results show that NBTXR3 activated by RT is safe and well tolerated at all doses with preliminary encouraging efficacy results. It thus represents a promising future treatment for frail and elderly pts with locally advanced HNSCC with limited therapeutic options. Expansion phase has started at the RP2D.

Clinical trial information: NCT01946867

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