- Primary endpoint was the pathological Complete Response Rate
- The main secondary endpoint was the resection margin status evaluating the quality of surgery
- NBTXR3 accumulates in tumors and is activated by radiation therapy
NANOBIOTIX (Euronext: NANO - ISIN: FR0011341205) announced on 6/22/2018 positive topline results of the Phase II/III act.in.sarc trial evaluating NBTXR3 in Soft Tissue Sarcoma (STS).
"Data are exceptional and show without any doubt an improvement of radiation therapy impact with a significant number of complete response. NBTXR3 can bring real benefit to patients and it can change the standard of care. This innovation will play a role in many other indications and particularly where radiotherapy is used alone."
Pr. Sylvie Bonvalot, MD, Head of Sarcoma and Complex Tumor Surgery Unit at Institut Curie, Paris, France and Global Principal Investigator of the PII/III study
NBTXR3 is a first-in-class product with a new mode of action physically destroying cancer cells when activated by radiation therapy. NBTXR3 is designed to directly destroy tumors and activate the immune system for both local control and systemic disease treatment.
The Phase II/III study was a prospective, randomized (1:1), multinational, open label and active controlled two-armed study of 180 patients with locally advanced STS. The objective of the Phase II/III trial was to evaluate the efficacy and the safety of NBTXR3 activated by radiotherapy compared to the standard of care (radiotherapy alone). Patients have been treated with the standard dose of radiation (25x2 Gy) and efficacy endpoints have been measured on surgically resected tumors.
The primary endpoint is the pathological Complete Response Rate (pCRR) defined as the rate of patients showing less than 5% of residual viable cancer cells in the tumor post treatment. This primary endpoint is related to NBTXR3's mode of action and product efficacy. Twice as many patients (16.1% vs 7.9%) achieved a pathological Complete Response (pCR) with NBTXR3 compared to the control arm (p = 0.0448). The significant difference observed between both arms validates the superiority of the treatment with NBTXR3 versus radiation alone.
The main secondary endpoint is the resection margin status evaluating the quality of surgery. The main objective is to achieve compartmental clean margins (negative margin defined as R0) i.e. no more cancer cells found within the surgical margins. NBTXR3 demonstrated a statistically significant increase in R0 surgical margin rate compared to radiotherapy alone (relative increase of 20%, p = 0.042). The resection with negative margins is a validated surrogate endpoint for systemic and long-term benefit for patients such as local progression free survival (PFS) and distant PFS.
The company is developing therapies using its NanoXray technology. The process works by first applying relevant coatings to hafnium oxide particles. Then particle size and coating enable accumulation in tumors. On exposure to ionizing radiation, the hafnium oxide contained in the nanoparticles generates large quantities of electrons, which amplify the dose of energy delivered to the tumor. The dose of X-ray delivered to the tumor is magnified, whilst the dose passing through healthy tissues remains unchanged.
NBTXR3 nanoparticles are designed to be administered by a single intratumoral injection directly into the tumor before the first radiotherapy session.