NBTXR3 for the treatment of locally advanced HNSCC in frail and/or elderly patients: a phase I/II study

RSNA 2019 · Le Tourneau C, Calugaru V, Garcia VM, Mirabel X, Doger B, Calvo E, et al.


Le Tourneau1, V. Calugaru1, V. Moreno Garcia2, X. Mirabel3, B. Doger2, E. Calvo2, J. Fijuth4, T. Rutkowski5, N. Magne6, M. Sanz Taberna7, J. Contreras8, I. Brana Garcia9, Z. Papai10, Z. Takacsi-Nagy11, X. Liem3, S. Salas12, S. Wong Hee Kam13, C. Florescu14, J.O. Thariat15, and C. Hoffmann1

1 — Institut Curie, Paris, France
2 — START Madrid, Madrid, Spain
3 — Centre Oscar Lambret, Lille, France
4 — Provita Prolife, Tomaszow Mazowiecki, Poland
5 — Skłodowska-Curie Institute of Oncology, Gliwice, Poland
6 — Lucien Neuwirth Cancer Institute, Saint Priest en Jarez, France
7 — Institut Catala d’Oncologia (ICO L’Hospitalet) Hospital Duran i Reynals, Barcelona, Spain
8 — Hospital Universitario Regional de Malaga, Malaga, Spain
9 — Vall D’Hebron Institute of Oncology, Barcelona, Spain
10 — Magyar Honvedseg Egeszsegugyi Kozpont, Budapest, Hungary
11 — National Institute of Oncology, Budapest, Hungary
12 — Assistance Publique Hôpitaux de Marseille, Timone Hospital, Marseille, France
13 — Hôpital Timone, APHM, Marseille, France
14 — Unicancer – François Baclesse Center, Caen, France
15 — Centre François Baclesse, Caen, France


Purpose: Elderly head and neck squamous cell carcinoma (HSNCC) patients (pts) ineligible for standard of care treatment require new therapeutic approaches. NBTXR3, hafnium oxide nanoparticles, may represent such an option. NBTXR3 is activated by radiotherapy, enhancing its effects, leading to physical destruction of cancer cells. A Phase I/II trial [NCT01946867] is underway to evaluate NBTXR3 in elderly (≥70 years) or frail pts with HNSCC of the oral cavity and oropharynx ineligible for cisplatin or intolerant to cetuximab.
Method and materials: Pts received a single intratumoral injection of NBTXR3 and intensity modulated radiation therapy (IMRT; 70 Gy/35 fractions/7 weeks). The study was a 3 + 3 dose escalation to test the NBTXR3 dose equivalent to 5, 10, 15, and 22% of baseline tumor volume, followed by a dose expansion. Primary endpoints include Recommended Phase 2 Dose (RP2D) determination and early dose limiting toxicities (DLT). Presence of NBTXR3 in surrounding healthy tissues and efficacy (RECIST 1.1 principles) were also evaluated.

Results: Enrollment for the dose escalation phase was completed at all dose levels: 5% (3 pts), 10% (3 pts), 15% (5 pts), and 22% (8 pts). No early DLT or SAE related to NBTXR3 or injection were observed. One G1 AE (asthenia; 22%) related to NBTXR3 and four AEs (G2 oral pain, G1 tumor hemorrhage, G1 asthenia, and G1 injection site hemorrhage) related to injection were reported. RT-related toxicity was as expected. The RP2D has been determined to be 22%. CT-scan assessment demonstrated absence of NBTXR3 in surrounding tissues. Among 13 evaluable pts treated at doses ≥10%, 9 achieved complete response of the injected lesion. The final dose escalation safety results will be presented herein.

Conclusion: NBTXR3 was well tolerated at all tested doses and demonstrated a good safety profile. A dose expansion phase has started with the identified RP2D.
NBTXR3 is currently being evaluated in a phase II/III trial in soft tissue sarcoma [NCT02379845] and phase I/II trials in prostate [NCT02805894], liver [NCT02721056] and rectal [NCT02465593] cancers.

Clinical relevance: The results of this study highlight the potential of NBTXR3 as a novel treatment option for elderly and/or frail pts with locally advanced HNSCC and address an unmet medical need.

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