Nanobiotix, a late clinical-stage nanomedicine company pioneering new approaches to the treatment of cancer, announced the US Food and Drug Administration (FDA) has approved its Investigational New Drug (IND) Application for NBTXR3, a first-in-class nanoparticle designed for direct injection into cancerous tumours, activated by stereotactic ablative radiotherapy (SABR) and administered in combination with an anti-PD1 antibody (nivolumab or pembrolizumab).
Laurent Levy, CEO of Nanobiotix, stated: "The FDA's approval of Nanobiotix's IND application for this trial is a major milestone for our company. We're ready and excited to launch our first immuno-oncology clinical trial in the US combining NBTXR3 with a checkpoint inhibitor. Advancing our demonstration of NBTXR3's potential to turn checkpoint inhibitor non-responders into responders could be game-changing, and the approach could address the unmet medical needs of a significant number of patients. Based on existing pre-clinical and clinical data, NBTXR3 could become a backbone in immuno-oncology."
The IND approval enables Nanobiotix to initiate NBTXR3-1100, a Phase I/II prospective, multi-center, open-label, and non-randomized clinical trial evaluating the efficacy and safety of NBTXR3 activated by SABR combined with checkpoint inhibitors (nivolumab or pembrolizumab). NBTXR3-1100 includes three cohorts of patients with recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC), or with metastatic non-small cell lung cancer (NSCLC). The study will be conducted in two consecutive phases. The first of these will be dose escalation, followed by a dose expansion phase. The study will seek to enroll between 36 to 72 patients in phase I and 40 patients in phase II.
NBTXR3-1100's dose escalation phase is based on a classical 3+3 phase I study and planned as a 3-level program to identify the appropriate dose of NBTXR3 injected into the tumor as well as the activation dose of SABR. While NBTXR3 and Radiotherapy doses will be escalated, the anti-PD1 antibody dose will remain constant. One approved anti-PD1 antibody for the dose expansion phase will be selected based on the preliminary risk-benefit ratio assessment observed in phase I portion of the trial.
Primary and secondary endpoints will evaluate efficacy and safety, while exploratory endpoints further characterize the treatment-induced genomic alterations previously reported, including enriched cytokine activity and markers of adaptive immune response and T-cell receptor signalling pathways.
The NBTXR3-1100 trial will be led by coordinating investigator Tanguy Seiwert, M.D., of The University of Chicago Medical Center, and principal investigator Jared Weiss, M.D., of The University of North Carolina - Chapel Hill.
The potential for immuno-oncology agents to boost immune system response by priming it for active attack against tumor cells has long been a source of excitement.
While the response to checkpoint inhibitors in so-called "hot" tumors, infiltrated by T-cells and characterized by an inflammatory profile, has been striking with long-lasting clinical benefits in some cancer patients, most patients exhibit little or no response to existing treatments.
According to published data, only 15% to 20% of non-small-cell lung cancer patients (NSCLC), and 13% to 22% of head and neck squamous cell carcinoma patients (NHSCC) respond to current immunotherapy treatments.
The physical mode of action by which NBTXR3 works induces a different immunogenicity and could be the key to significantly increasing the number of cancer patients who can benefit from immuno-oncology therapies.
As presented earlier this year at ASCO & SITC 2017, NBTXR3 activated by radiotherapy was shown to induce a specific adaptive immune pattern that could potentially convert a non-responder into an immune-responsive patient receptive to treatment with available checkpoint inhibitors.
On top of NBTXR3's core developments as a single agent across seven oncology indications, Nanobiotix's immuno-oncology combination program opens the door to new developments, potential new indications, and important value creation opportunities.
The first patient first visit in the potentially paradigm changing trial is expected in Q2 2018 with first expected results in the summer of 2019.
NBTXR3 is an injectable aqueous suspension of hafnium oxide nanoparticles designed as an innovative therapeutic agent for the treatment of solid tumours, currently in clinical development by Nanobiotix.
Once injected intratumorally, NBTXR3 can deposit high energy within tumours only when activated by an ionizing radiation source, notably radiotherapy. Upon activation, the high energy radiation is physically designed to kill the tumor cells by triggering DNA damage and cell destruction and improve clinical outcomes.
Promising results indicate that NBTXR3 activity could be applicable across solid tumours triggering immunogenic cell death, leading to an immune response, reinforcing a local and potentially systemic effect, and contributing to transform "cold" tumours into "hot" tumours. NBTXR3's major characteristics are represented by a high degree of biocompatibility, one single administration before and during the whole therapy and the ability to fit into current standards of radiotherapy care.
NBTXR3 entered clinical development in 2011 in a phase I/II with patients suffering from advanced soft tissue sarcoma of the extremities and is currently in the final stages of its subsequent phase II/III. In parallel, it is currently being tested in numerous phase I/II clinical trials with patients suffering from locally advanced squamous cell carcinoma of the oral cavity or oropharynx (head and neck), liver cancer (hepatocellular carcinoma and liver metastasis), locally advanced or unresectable rectal cancer in combination with chemotherapy, head and neck cancer in combination with concurrent chemotherapy, and prostate adenocarcinoma.