Topline results announced of the Phase II/III act.in.sarc trial, evaluating NBTXR 3 in SoftTissue Sarcoma- Nanobiotix.

Nanobiotix, a late clinical-stage nanomedicine company pioneering new approaches in the treatment of cancer, announced positive topline results of the Phase II/III act.in.sarc trial, evaluating NBTXR 3 in SoftTissue Sarcoma (STS).

�Data are exceptional and show without any doubt an improvement of radiation therapy impact with a significant number of complete response. NBTXR 3 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.

NBTXR 3 is a first-in-class product with a new mode of action physically destroying cancer cells when activated by radiation therapy. NBTXR 3 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 NBTXR 3 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. Primary endpoint achieved in the intend-to-treat population (ITT) : 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 NBTXR 3�s mode of action and product efficacy. Twice as many patients (16.1% vs 7.9%) achieved a pathological Complete Response (pCR) with NBTXR 3 compared to the control arm (p = 0.0448). The significant difference observed between both arms validates the superiority of the treatment with NBTXR 3 versus radiation alone. Secondary Endpoint : achieved in the ITT - Resection margins status and operability. 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. NBTXR 3 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.

Safety and feasibility: NBTXR 3 demonstrated a good local tolerance among this patient�s population. Findings showed a very similar radiation-related safety in both arms. The patients in both the control and tested arms of the study received the planned radiotherapy (dose and schedule). Notably, feasibility and follow-up of surgery were also equivalent.

Acute immune adverse events of short duration observed in 7.9% of patients. The Injection site caused pain in 13.5% of patients. In addition, 6.7% of patients experienced grade 1 injection site hematoma / ecchymosis. Regarding long-term toxicity, less serious adverse events were reported for NBTXR 3 arm.

Comment: Currently, the company is evaluating NBTXR 3 in seven clinical trials with a focus on head and neck cancers and Immuno-Oncology programs.