887P - Antitumor activity of the radioenhancer NBTXR3 on injected lesions to estimate overall survival: Exploratory analyses from a phase I in cisplatin-ineligible locally advanced HNSCC patients

Background

Assessment of treatment effect on surrogate and OS outcomes is a challenge for novel therapies. NBTXR3 is a first-in-class radioenhancer, composed of hafnium oxide nanoparticles, injected once intratumorally (IT) and activated by radiotherapy (RT) amplifying RT anti-tumoral response. Preliminary signs of NBTXR3 anti-tumor activity were evaluated in the dose expansion part of a phase I in cisplatin-ineligible patients (pts) with LA-HNSCC. Due to the unique features of NBTXR3, exploratory analyses aimed at defining if anti-tumor activity is a valuable metric for estimating OS.

Methods

Analyses were performed in 56 pts treated (April 2019-January 2022) with IT NBTXR3 in primary tumor followed by RT for primary tumor and involved lymph node. 44 pts were evaluable for objective tumor response. Correlation between response-related endpoints of IT lesion and LPFS with OS were compared with those using overall response and PFS. Restricted mean survival time (RMST) analyses were performed to assess if the RMST of response duration of the IT lesion and LPFS could estimate the probability of “success” for OS over clinically meaningful time points.

Results

In the evaluable population, best IT lesion and overall response rates were 81.8% and 79.5%, respectively: CR of 63.6% for IT lesion and 52.3 % for overall lesions. Median duration of response of IT lesion and overall lesions were 19 and 12 months, respectively. OS was 23 Months. Correlation between IT lesion response, LPFS, and OS tends to be higher than between overall response, PFS, and OS. RMST of LPFS and IT lesion response duration are closer to RMST of OS than PFS and overall response duration for all timepoints.

Conclusions

NBTXR3 radioenhancement may drive the objective response duration effect as noted in the difference between injected and non-injected lesions treated with the same dose of RT. Correlation and RMST analyses suggest that NBTXR3 effects on injected lesions might better estimate OS. These results support our ongoing phase III NANORAY-312 study design which allows injection of involved lymph nodes, and might be translated in higher OS than in our phase I.

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. Z. Takacsi-Nagy: Financial Interests, Personal, Speaker, Consultant, Advisor: Nanobiotix. X. Liem: Financial Interests, Personal, Speaker, Consultant, Advisor: Nanobiotix. V. Moreno Garcia: Financial Interests, Personal, Advisory Board: BMS, Janssen, Roche, Basilea, Bayer, AstraZeneca; Financial Interests, Personal, Full or part-time Employment: START; Financial Interests, Institutional, Local PI, AbbVie, AceaBio, Adaptimmune, ADC Therapeutics, Aduro, Agenus, Amcure, Amgen, Astellas, AstraZeneca Bayer BeiGene BioInvent International AB, BMS, Boehringer, Boheringer, Boston, Celgene, Daiichi Sankyo, Debiopharm, Eisai, e-Terapeutics, Exelisis, Forma Therapeutics, Genmab, GSK, Harpoon, Hutchison, Immutep, Incyte, Inovio, Iovance, Janssen, Kyowa Kirin, Lilly, Loxo, MedSir, Menarini, Merck, Merus, Millennium, MSD, Nanobiotix, Nektar, Novartis, Odonate Therapeutics, Pfizer, Pharma Mar, PharmaMar, Principia, PsiOxus, Puma, Regeneron, Rigontec, Roche, Sanofi, Sierra Oncology, Synthon, Taiho, Takeda, Tesaro, Transgene, Turning Point Therapeutics, Upshersmith.: Multiple. E. Calvo: Financial Interests, Personal, Advisory Board: Adcendo, Amunix, Anaveon, AstraZeneca, BMS, Janssen, MonTa, MSD, Nanobiotix, Nouscom, Novartis, Servier, TargImmune, T-knife, Chugai, Elevation Oncology, Ellipses Pharmacy, SyneosHealth, Genmab, Diaccurate; Financial Interests, Personal, Invited Speaker: OncoDNA, PharmaMar, Roche/Genentech; Financial Interests, Personal, Full or part-time Employment, Director, Clinical Research: HM Hospitales Group; Financial Interests, Personal, Full or part-time Employment, Medical Oncologist. Clinical Investigator. Director, Clinical Research: START Madrid - CIOCC (Centro Integral Oncológico Clara Campal); Financial Interests, Personal, Member of Board of Directors, External Independent member of Board of Directors: PharmaMar; Financial Interests, Personal, Ownership Interest: START, Oncoart Associated; Financial Interests, Personal, Steering Committee Member, Member of Data Monitoring Committee: BeiGene, Sanofi, Merus; Financial Interests, Personal, Steering Committee Member: Novartis; Non-Financial Interests, Other, Non-for-profit Foundation. President and co-founder: INTHEOS (Investigational Therapeutics in Oncological Sciences) non-for-profit Foundation; Non-Financial Interests, Advisory Role: PsiOxus; Non-Financial Interests, Other, Chair of the Independent Data Monitoring Committee: EORTC IDMC; Non-Financial Interests, Member of Board of Directors, Non-for-profit Foundation, trustee member: Non-for-profit Foundation PharmaMar; Non-Financial Interests, Advisory Role, Non-for-profit foundation: CRIS Cancer Foundation, non-for-profit ; Non-Financial Interests, Member: ASCO, ESMO, SEOM, EORTC. A. Debard, L. Finzi, O.I. Vivar, L.A. Farber: Financial Interests, Personal, Full or part-time Employment: Nanobiotix. M. Lesnik: Financial Interests, Personal, Speaker, Consultant, Advisor: Nanobiotix. All other authors have declared no conflicts of interest.