FDA approves Nanobiotix’s first immuno-oncology trial: A Phase I/II study of NBTXR3 activated by radiation therapy for patients with non-small cell lung cancer or head and neck squamous cell carcinoma cancer treated with an anti-PD1 antibody.
Nanobiotix, a late clinical-stage nanomedicine company pioneering new approaches to the treatment of cancer, announced that the U.S. Food and Drug Administration has approved its Investigational New Drug application for NBTXR3, a first-in-class nanoparticle designed for direct injection into cancerous tumors, activated by stereotactic ablative radiotherapy and administered in combination with an anti-PD1 antibody (nivolumab or pembrolizumab).
The Investigational New Drug 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 stereotactic ablative radiotherapy 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, or with metastatic non-small cell lung cancer. 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 stereotactic ablative radiotherapy. 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 signaling 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 interest.
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 percent to 20 percent of non-small-cell lung cancer patients, and 13 percent to 22 percent 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, 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 may open the door to new developments, potential new indications, and creation opportunities.
The first patient first visit in the trial is expected in Q2 2018 with with first expected results in the summer of 2019.
Filed Under: Drug Discovery