NBTXR3 in advanced liver cancers

ASTRO, Virtual, 2020, de Baère T. et al.

Authors

Thierry de Baère1, Marc Pracht2, Yann Rolland2, Jérôme Durand-Labrunie1, Nicolas Jaksic2, France Nguyen1, Jean-Pierre Bronowicki3, Véronique Vendrely4, Valérie Croisé-Laurent3, Emanuel Rio5, Samuel Le Sourd2, Patricia Said6, Pierre Gustin1, Christophe Perret5, Didier Peiffert7, Eric Deutsch1, Enrique Chajon2

1 – Institut Gustave Roussy, Villejuif, France
2 – Centre Eugene – Marquis, Rennes, France
3 – CHRU de Nancy – Hôpital de Brabois, Vandoeuvre-lès-Nancy, France
4 – CHU de Bordeaux – Hôpital Haut-Lévêque, Pessac, France
5 – Institut de cancérologie de l’Ouest, Nantes, France
6 – Nanobiotix, SA, Paris, France
7 – Radiotherapy, Institut de Cancérologie de Lorraine, Nancy, France

Summary

Background: Stereotactic body radiotherapy (SBRT) is a well-tolerated and valuable alternative for patients with unresectable hepatocellular carcinoma (HCC) or liver metastases (mets) who are not eligible for standard treatment such as surgery, local ablation or chemoembolization. Yet, the energy dose delivered to the tumor is limited due to potential toxicity to healthy tissues and the need to preserve liver function. Thus, achieving local control in liver cancers remains a challenge. The first-in-class radioenhancer NBTXR3 (hafnium oxide nanoparticles), administered by intratumoral (IT) injection once prior to RT treatment, augments the energy dose deposit within tumor cells when activated by RT. The result is increased tumor cell death compared to RT alone without increasing radiation exposure to surrounding tissues. Patients with HCC or mets may benefit from this new approach. Here we report on a phase I/II study evaluating NBTXR3 activated by SBRT in these patients.

Methods: In the phase I part of the study [NCT02721056], five NBTXR3 dose levels equivalent to 10, 15, 22, 33, and 42% of baseline tumor volume are tested following a traditional 3+3 design. NBTXR3 is administered by IT injection followed by SBRT (45 Gy / 3 fractions / 5-7 days or 50 Gy / 5 fractions / 15 days). Primary endpoints include determination of the recommended phase 2 dose (RP2D) based on the incidence of the early DLTs. Secondary endpoints include the safety profile, liver disease scores evolution, and early efficacy by target lesions response rate (mRECIST/RECIST 1.1).

Results: To date, 22 patients have been treated and the 4 first dose levels are completed with 6 patients at 10% (2 SBRT doses tested due to organ constraints), 4 patients each at 15% and 22% (due to fiducial displacement and incomplete injected dose) and 3 patients at 33%. The last dose level (42%) is ongoing with 5 patients treated so far. No early DLT has been observed at any dose level. Five AEs (3 G1-2; 2 G3) related to the injection and 4 AEs related to NBTXR3 (3 G1-2; 1 G3), including 1 SAE (bile duct stenosis, also related to RT) were observed. No grade 4-5 AEs were observed. CT-scan showed no leakage of NBTXR3 into surrounding healthy tissues and SBRT safety profile was as expected. No clinically meaningful changes in CPS and APRI were observed post-treatment. In patients evaluable for efficacy, best observed target lesion responses were 5 complete response and 3 partial response in HCC patients (n=8) and, 5 partial response and 1 stable disease in liver mets patients (n=6).

Conclusions: NBTXR3 intratumoral injection is feasible and NBTXR3 demonstrates a very good safety and tolerability profile thus far. Recruitment is nearly completed at the 42% dose level. Early efficacy results highlight the potential for NBTXR3 to improve the clinical outcomes of patients with unresectable primary or metastatic liver cancer.

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.

CloseFermer