Date: 2015-06-09
Type of information: DSMB assessment
phase: 1-2
Announcement: DSMB assessment
Company: Nanobiotix (France)
Product: NBTXR3
Action
mechanism: NBTXR3 is a nanoparticle consisting of hafnium oxide crystals and it is intended to enhance the local destruction of the tumor mass during radiotherapy. Once injected into the tumor, NBTXR3 accumulates in the cancer cells. Due to the physical properties of hafnium oxide, the particles emit huge amounts of electrons upon radiation. This leads to the formation of radicals within the tumor cell, which in turn damage the cancer cells and cause their targeted destruction. NBTXR3 particles are inert and emit electrons only during their exposure to radiotherapy. As a result, the destructive power of standard radiation therapy could be locally and selectively enhanced within the tumor cells.
Disease: head and neck cancer
Therapeutic area: Cancer - Oncology
Country: France
Trial
details: The phase I trial will be an open-label non-randomized, dose escalation study of safety and tolerability evaluation of NBTXR3. The product will be implanted by intra-arterial (IA) or intra-tumor (IT) injection, and activated by high precision radiation therapy (Intensity-modulated radiation therapy - IMRT) delivered as per current medical practice. Patients with locally advanced squamous cell carcinoma of the oral cavity or oropharynx constitute the targeted population which includes frail and elderly patients. Two different administration schedules of NBTXR3 will be investigated simultaneously in 2 different groups of patients. Allocation of patients to the intra-tumor injection or intra-arterial injection depends on the patient and tumor singularity. Based on the observed safety, the recommended doses for further evaluation of NBTXR3 as intra-arterial or intra-tumor injection with radiotherapy will be selected.
The secondary objectives of the study include assessment of the tumor Response Rate and complete Response Rate by MRI, and the evaluation of local and general Progression Free Survival of NBTXR3. Furthermore, the feasibility of local administration, either intra-tumor or intra-arterial injection of NBTXR3, then activated by radiotherapy will be evaluated. Approximately, 24 patients are expected to be treated in any schedule (IT or IA) of the trial, with a total of maximum 48 patients.
Latest
news: * On June 9, 2015, Nanobiotix announced positive preliminary safety results for its lead NanoXray product NBTXR3, in its head and neck cancer Phase I/II clinical trial. An independent safety committee of experts just gave a positive assessment of the safety profile of NBTXR3 injection, based on the 2 first dose levels preliminary results of the phase I/II of Head and Neck clinical trial. The intermediate results show the feasibility of NBTXR3 injection at the 2 first dose levels evaluated. Volumes equivalent to 5% and 10% of the tumor size have been tested by intra tumoral injection. For the record, 10% is the recommended volume in the Soft Tissue Sarcoma indication, currently evaluated in a study for registration (phase II/III). These results also confirm NBTXR3 good safety profile, as no Serious Adverse Events related to the product have been observed and as the product appears to stay within the tumor with no leakage in the surrounding healthy tissues. In this trial, patients are being assessed particularly on their tolerance to the product. Exploratory efficacy endpoints will be evaluated and shown at the end of this clinical trial. The first part of this phase I/II clinical trial has targeted frail and elderly patients who cannot receive chemotherapy with radiotherapy and need new innovative treatments. These patients represent approximately 11% of the Head and Neck cancer population.
The positive safety results on the first levels and additional preclinical data that have been generated, allow to enlarge the scope of patients that could be targeted within the Head and Neck indication. As a consequence, Nanobiotix plans to include in the continuation of this Phase I/II clinical trial, patients that are receiving cisplatin in combination with radiotherapy. Currently, the combinasion of Cisplatin with radiotherapy is given to 35-40% of patients with Head and Neck carcinomas. The inclusion of these patients would magnify the total potential treatable population for NBTXR3 in this indication.
* On June 13, 2013, Nanobiotix has announced that its lead compound NBTXR3 has received authorization from the French Medicine Agency, ANSM, to start a clinical trial in patients with locally advanced cancers of the oral cavity or oropharynx (head and neck cancer), at the Institut Curie, Paris, France, a French leading cancer treatment center. This represents a second indication for NBTXR3 which is also in clinical trials for soft tissue sarcoma.
