NBTXR3 in the treatment of liver cancers

ASCO, Chicago · 2019, E. Chajon et al.


Enrique Chajon1, Marc Pracht1, Yann Rolland11, Thierry de Baere2, France Nguyen2, Jean-Pierre Bronowicki3, Véronique Vendrely4, Antonio Sa Cunha7, Anne-Sophie Baumann5, Valérie Croisé-Laurent3, Emanuel Rio6, Samuel Le Sourd1, Pierre Gustin2, Christophe Perret6, Didier Peiffert55, Eric Deutsch2

1 – Centre Eugene – Marquis, Rennes, FR
2 – Institut Gustave Roussy, Villejuif, FR
3 – Hôpital de Brabois, Vandoeuvre Les Nancy, FR
4 – Groupe Hospitalier Sud – Hôpital Haut-Lévêque, Pessac, FR
5 – Institut de Cancérologie de Lorraine, Nancy, FR
6 – Institut de cancérologie de l’Ouest, Nantes, FR
7 – Centre Hépato-Biliaire Paul Brousse, Villejuif, FR


Background: Hafnium oxide nanoparticles, NBTXR3, increase the effect of radiotherapy (RT) by enhancing local energy dose deposit within tumor cells, resulting in increased cell death compared to the same dose of RT alone. NBTXR3 efficacy was demonstrated in a phase II/III study in soft tissue sarcoma (NCT02379845) and is currently evaluated in other solid tumors including liver cancers. The use of this radio enhancer is particularly relevant in liver cancer management, a difficult to treat heterogenous population, due to the presence of underlying liver dysfunction.

Methods: Phase I/II study of NBTXR3 activated by RT in patients (pts) with HCC (with/without portal vein tumor thrombus) or liver metastasis (mets) [NCT02721056]. The dose escalation part followed a 3+3 design with tested dose levels equivalent to 10%, 15%, 22% and 33% of baseline tumor volume. Patients were treated with a single intralesional injection (ILI) of NBTXR3 followed by Stereotaxic Body RT (SBRT: 45 Gy/3 fractions/5 to 7 days). Determination of recommended dose(s) and early dose limiting toxicities (DLT) were primary endpoints. Secondary endpoints include assessment of global safety profile, liver function evaluated by Child-Pugh score (CPS), AST to Platelet Ratio Index (APRI), and response rate (mRECIST/RECIST 1.1).

Results: The 4 levels of ILI dose escalation were finalized (n = 17): 6 pts at 10% (2 SBRT doses tested due to organs constraints), 4 pts at 15% and 22% (due to fiducial displacement and ILI shift) and 3 pts at 33% were included. ILIs were successful and SBRT was delivered as planned with no observed DLT or NBTXR3-related SAE at all levels. Only one grade 1 AE (fatigue) related to NBTXR3 was reported at dose level 33%. No relevant change of CPS or APRI was observed over time. Among 7 evaluable HCC pts the best target lesion responses by mRECIST were: 3 CR and 4 PR and among 5 evaluable mets pts: 2 PR, 1 SD and 2 PD.

Conclusions: This study demonstrated the feasibility and good tolerance of the first in class NBTXR3 ILI. These results have supported a protocol amendment adding a higher dose of NBTXR3 (42% of the tumor volume). This innovative approach might constitute a valuable solution for patients with unresectable liver tumors and liver dysfunction.

Clinical trial information: NCT02721056

By continuing to use the site, you agree to the use of cookies.En poursuivant votre navigation sur ce site, vous acceptez l’utilisation de cookies. More information.En savoir plus.

The cookie settings on this website are set to “allow cookies” to give you the possibility to switch between languages in a way that this will not interfere with page navigation. If you continue to use this website without changing your cookie settings or you click “Accept” below then you are consenting to this.Par défaut, les paramètres de ce site autorisent les cookies pour vous permettre notamment de naviguer entre les différentes langues disponibles. Nous utilisons des cookies pour vous proposer un site internet facile d'utilisation, sécurisé et fonctionnel. Si vous les autorisez également, cliquez sur « Accepter » ou poursuivez simplement votre navigation.