A Phase I-II Study of NBTXR3 Activated by Sterostatic Body Radiation Therapy (SBRT) In the Treatment of Liver Cancers

PHASE I PART: Dose escalation and Recommended Dose (Volume) The purpose of the Phase I part of the study is to determine the Recommended Dose (volume), the safety profile and the feasibility of the treatment of NBTXR3 administered either by intrahepatic lesion injection or super selective transcatheter arterial injection and activated by stereotactic body radiation therapy (SBRT), in patients with liver cancers. Primary objective

• To determine the Recommended Dose(s) (volume(s)) and the early Dose Limiting Toxicity (DLT) of NBTXR3 administered either by intralesional injection or by super selective transcatheter arterial injection and activated by stereotactic body radiation therapy (SBRT) in patients with liver cancers

PHASE II PART: Safety and Efficacy evaluation Primary objectives

The primary objectives of the Phase II part are:

• To assess and characterize the safety profile, including liver function evaluation using MELD/MELD-Na and Child-Pugh scores, of NBTXR3 activated by SBRT, at the Recommended Dose(s)(Volume(s)) as determined previously in the Phase I part, in patients with liver cancers Clinical Investigation Plan - NBTXR3/103
• To evaluate the antitumor activity in terms of Complete Response Rate (CRR) of target lesions, as per mRECIST for HCC and RECIST version 1.1 for liver metastases at 12 weeks' post radiotherapy, of NBTXR3 activated by SBRT, at the Recommended Dose(s) (Volume(s)) as determined previously in the Phase I part, in patients with liver cancer.