Date: 2015-11-13
Type of information: update on patient enrollment
phase: 2-3
Announcement: update on patient enrollment
Company: Nanobiotix (France)
Product: NBTXR3
Action
mechanism: nanoparticle. 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: soft tissue sarcoma
Therapeutic area: Cancer - Oncology
Country: Belgium, Canada, France, Hungary, The Netherlands, Poland, Romania, South Africa, Spain
Trial
details: A multi-center randomized, open-label, two-arm Phase II/III trial in patients with locally advanced soft tissue sarcoma of the extremity and trunk wall. Patients in the experimental treatment arm (Arm A) will receive an intratumoral injection of NBTXR3 followed by radiotherapy and surgery. Patients in the control arm (Arm B) will be treated with radiotherapy alone followed by surgery only. It is expected to enroll approximately 180 patients to have 78 evaluable patients in each arm. The primary objective of this study is to increase the pathological complete response rate (pCR) of intratumoral injection of NBTXR3 activated by external beam radiation therapy (EBRT), versus EBRT alone in patients with locally advanced STS of the extremity and trunk wall. Secondary objectives are to assess the safety profile of NBTXR3 activated by radiotherapy (incidence of early and late adverse events), to compare the objective response rate (ORR), tumor volume changes after NBTXR3 and carcinological resection rates, and to evaluate limb amputation rates. Exploratory objectives are to assess the tumor response, to evaluate the time-to-local recurrence, Local Recurrence Rate (LRR) at 12 months and to evaluate the time-to-distant recurrence and Distant-Recurrence Rate (DRR) at 12 months. Based on the results of the Phase I pilot trial, the recommended NBTXR3 volume for the pivotal study is equivalent to 10% of the tumor volume. Hence, the injected amount of NBTXR3 will be based on each patient’s tumor volume as determined by MRI. (NCT02379845)
Latest
news: * On November 13, 2015, Nanobiotix announces the expansion of its pivotal phase II/III trial for NBTXR3 in Soft Tissue Sarcoma (“act.in.sarc” study) in 29 sites in 7 countries. The patient recruitment rate is increasing in line with the Company’s expectations. The international multi-center pivotal study (phase II/III) began end of 2014 in France. By June 2015, the trial was running in 12 European clinical centers of reference in France, Belgium, Spain and Hungary. Three additional countries (Poland, Romania and South-Africa) and 17 additional clinical centers are now involved. Clinical authorization requests are ongoing in Canada and other Asia-Pacific and European countries. This study is expected to be the final step before CE mark which is anticipated towards the end of 2016. * On May 11, 2015, Nanobiotix announced the expansion of the pivotal phase II/III trial for NBTXR3 in Soft Tissue Sarcoma (STS). The pivotal phase trial was launched following positive phase I results presented at ASCO 2014, which provided NBTXR3 proof of concept data. This international multi-center pivotal study is expected to be completed towards the end of 2016 (156 patients) with interim results in mid-2016 (104 patients). The results will mark the last step required before product registration (CE mark) which is anticipated towards the end of 2016. The trial is already running in clinical centers of excellence in four European countries so far (France, Belgium, Spain, Hungary) and clinical authorization requests are ongoing in other European countries. This is in line with Nanobiotix’s strategy to broaden the number of trial sites up to 25-30. Patient recruitment rate is increasing in opened centers; in the past 30 days, 10 patients have been recruited. Beyond Europe: Nanobiotix’s Taiwanese partner PharmaEngine which joined the pivotal trial to accelerate NBTXR3’s development in the Asia-Pacific Region, will develop the trial in several Asian countries. Clinical request has also been requested for this NBTXR3 pivotal trial in Canada, in line with Nanobiotix’s strategy for North America. The trial will compare the antitumor activity of NBTXR3 (administered by intratumoral injection) and radiotherapy compared with radiotherapy alone. Patients in both treatment arms will have a regular protocol which means five weeks of radiotherapy, followed by surgical resection of the tumor. An interim efficacy analysis will be performed once two-thirds of patients have been recruited, it is expected mid 2016. An Independent Data Monitoring Committee (IDMC) will be in charge of the reviewing the formal statistical interim analysis, to ensure the safety of all patients enrolled in the study, the quality of the data collected and the continued scientific validity of the study design. * On October 16, 2014, Nanobiotix announced that it has received approval from the French National Security Agency for Medicines and Health Products (ANSM) to start its Phase II/III registration trial of its lead product, NBTXR3, in patients with locally advanced soft tissue sarcoma (STS). This international multi-center pivotal study will start in France and then be conducted in around 25-30 sites throughout Europe once further authorizations are received. This pivotal trial is expected to be the final step before registration in Europe (CE mark) and should be –completed towards the end of 2016. In the Asia-Pacific region, as announced recently, PharmaEngine intends to participate in this pivotal study by opening clinical sites in several countries.
In parallel, Nanobiotix is establishing industrialization, market access and reimbursement strategies for NBTXR3 to prepare for a potential product launch at the end of 2016.
