A Phase I Study of NBTXR3 Activated by Radiotherapy for Patients with Advanced Cancers Treated With an Anti-PD-1 Therapy

Annals of Oncology, 2019 · Dicker AP, Shen C, De Baere T, Hoffmann C, Welsh JW, Rolland Y, et al.


C.Shen1, K.Jameson2, J.Weiss1T.Hackman3, D.Corum2, J.A.Akulian4, R.Dixon1, A.Pearson5, J.Frakes6, P.Said7, H.Miraoui2, E.Baskin-Bey8, T.Seiwert9

1 — Radiation Oncology, University of North Carolina, Chapel Hill, NC, USA
2 — Clinical Development, Nanobiotix SA, Cambridge, MA, USA
3 — Department of Otolaryngology and Head and Neck Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
4 — Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
5 — Medicine, University of Chicago, Chicago, IL, USA
6 — Radiation Oncology, Moffitt Cancer Center, Tampa, FL, USA
7 — Biometry, Nanobiotix SA, Paris, France
8 — CMO, Nanobiotix SA, Paris, France
9 — Oncology, Johns Hopkins, Baltimore, MD, USA


Background and Rationale: The majority of cancer patients are resistant to immune therapy; only around 15% respond to immune checkpoint inhibitors (ICI). Thus, strategies able to increase ICI response are of great interest. Recent work suggests radiotherapy (RT) can act as an immunomodulator to increase the proportion of ICI responders and improve clinical outcomes. However, RT dose and ultimate efficacy are limited by toxicity related to exposure of healthy tissues. NBTXR3 is a first-in-class radioenhancer administered by intratumoral injection, designed at the nanoscale to increase RT energy dose deposition within the tumor. The result is increased radiation-dependent tumor cell killing, without increasing radiation exposure of healthy tissues. Preclinical and early clinical data suggest NBTXR3 activated by RT can increase the anti-tumor immune response, producing both local and systemic (abscopal) effects. We hypothesize that NBTXR3 activated by RT, in combination with anti-PD-1 therapy (R3/RT/PD-1), will act synergistically to maximize the local RT effect while also producing a systemic response sufficient to increase the proportion of ICI responders or convert ICI non-responders to responders.

Clinical Trial Design: NANORAY-1100 [NCT03589339] is a multicenter, open-label, phase 1 study to evaluate safety and tolerability of R3/RT/PD-1 in three cohorts: (1) Locoregional recurrent or recurrent and metastatic head and neck squamous cell carcinoma (HNSCC) amenable to re-irradiation of the HN field, (2) Lung metastases from any primary cancer eligible for anti-PD-1, or (3) Liver metastases from any primary cancer eligible for anti-PD-1. Approximately two-thirds of each cohort will be composed of anti-PD-1 non-responders. NBTXR3 injection volume is based on a percentage of gross tumor volume (GTV) determined by central review. The primary objective is to determine R3/RT/PD-1 RP2D. Secondary objectives are to evaluate anti-tumor response (objective response rate; ORR) of R3/RT/PD-1, safety and feasibility of NBTXR3 injection, and NBTXR3 body kinetic profile. Exploratory objectives will assess biomarkers of R3/RT/PD-1 response, including PD-L1 status by IHC, mRNA and cytokine immune marker profiling.

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