Abstract 417P
Background
New approaches are needed for frail or elderly patients (pts) with locally advanced head and neck squamous cell carcinoma (LA HNSCC) unfit to concurrent cisplatin radiotherapy (RT). NBTXR3 (functionalized hafnium oxide nanoparticles) is a first-in-class radioenhancer that locally amplifies RT anti-tumoral response without adding toxicity to surrounding healthy tissue. This two-part study: dose-escalation followed by the dose-expansion part reported here, evaluated safety and preliminary efficacy of NBTXR3+RT in elderly or frail cisplatin ineligible pts.
Methods
Previously untreated pts with AJCC 8th Stage III-IVA or T3,T4 oral cavity or oropharynx (OPC) SCC received NBTXR3 IT injection at RP2D (22% baseline tumor volume) followed by IMRT (70 Gy, 35 fractions). Primary objectives were RP2D safety, and preliminary evidence of efficacy. Secondary objectives included PFS and OS.
Results
56 pts were treated from April 2019-January 2022; 44 were evaluable for objective tumor response. All treated (AT) population median age: 72 years. 67% had age-adjusted Charlson Comorbidity Index scores ≥4, 55.4% had OPC (45.2% HPV+) and 80% had T3-4. Median NBTXR3 injected volume was 13.6 [0.6-57.1] mL. Grade ≥ 3 treatment emergent adverse events (TEAE) reported as potentially related to NBTXR3 or injection procedure were 1.3% of all TEAEs. In the evaluable (EV) population, ORR of NBTXR3 injected lesion was 81.8%; complete response rate was 63.6%. ORR of injected and non-injected lesions was 79.5%. Median PFS by independent central review was 11.4 mos (AT) and 16.9 mos (EV). Median OS was 18.1 mos (AT) and 23.1 mos (EV). PFS of injected lesion (LPFS) was 16.9 mos (AT) and not reached (EV). Exploratory analyses of additional endpoints will be presented.
Conclusions
NBTXR3 IT injection followed by activation with RT was confirmed feasible and well tolerated in elderly or frail LA HNSCC pts with significant comorbidities. High ORR suggests NBTXR3+RT is effective. These results support our ongoing phase III study comparing NBTXR3/RT±cetuximab vs. RT±cetuximab in platinum-based chemotherapy ineligible elderly pts with LA-HNSCC: NANORAY 312 (NCIT04892173).
Clinical trial identification
NCT01946867.
Editorial acknowledgement
Legal entity responsible for the study
Nanobiotix.
Funding
Nanobiotix.
Disclosure
C. Le Tourneau: Financial Interests, Personal, Advisory Board: BMS, MSD, Merck Serono, Nanobiotix, Roche, Rakuten, Seattle Genetics, GSK, Celgene, ALX Oncology, Exscientia. X. Liem: Financial Interests, Personal, Invited Speaker: Nanobiotix. L. Finzi, A. Debard, O.I. Vivar: Financial Interests, Personal, Full or part-time Employment: Nanobiotix. All other authors have declared no conflicts of interest.