In an interview with PharmaShots, Laurent Levy, Co-Founder & CEO at Nanobiotix shares his views on the first patient enrollment of NBTXR3 in P-III (NANORAY-312) study for the treatment of head and neck squamous cell carcinoma

Shots:

• The first patient has been enrolled in P-III (NANORAY-312) study to evaluate the efficacy & safety of NBTXR3 with/out cetuximab vs radiotherapy with/out cetuximab in a ratio (1:1) in 500 patients with LA-HNSCC across US, EU & Asia. The study is based on the P-I (Study 102)
• The 1EPs of the study are PFS & 2EPs include OS, response rates & QoL. The company is expected a futility analysis at 18mos. & interim in 30mos.
• Preliminary data showed that the treatment was feasible & well tolerated while an exploratory efficacy showed a high target lesion ORR (85.4%), CR rate (63.4%), m-PFS (10.6 mos.) & m-OS of 18.1mos. in the evaluable patient population. NBTXR3 has received FTD from the US FDA

Tuba: Tell us more about NANORAY-312.

Laurent Levy: As our press release indicates, NANORAY-312 is an open-label, two-arm, randomized phase III registration study designed to investigate the efficacy and safety of radiotherapy-activated NBTXR3 with or without cetuximab versus radiotherapy alone with or without cetuximab in high-risk, cisplatin-ineligible elderly patients with locally advanced head and neck squamous cell carcinoma. The reason that this study is important has everything to do with the fact that elderly patients with locally advanced head and neck cancer desperately need new options for treatment.

Tuba: Please share with us the trial designs and results of the study

Laurent Levy: As we have only recently launched enrollment for the NANORAY-312 study, there are no results available from this study as yet. Regarding the trial design, individual study investigators will have the choice of whether to prescribe cetuximab to eligible patients as part of the study. Once the investigator’s choice has been made, patients will be randomized to receive NBTXR3 plus radiotherapy or radiotherapy alone at a 1:1 ratio

Tuba: Discuss the clinical MOA, ROA of the NANORAY-312

Laurent Levy: NBTXR3 is a novel, potentially first-in-class oncology product composed of functionalized hafnium oxide nanoparticles that are administered via one-time intratumoral injection and activated by radiotherapy. The product candidate’s physical mechanism of action (MoA) is designed to induce significant tumor cell death in the injected tumor when activated by radiotherapy, subsequently triggering an adaptive immune response and long-term anti-cancer memory. Please see the attached infographic which describes and illustrates the mechanism of action and route of administration of NBTXR3 for more information.

Tuba: Can we have a glance at the U.S FDA approval of NANORAY-312

Laurent Levy: While we cannot offer any specific insights at this time as to the exact timing of potential FDA approval of NBTXR3, we can say that the U.S. Food and Drug Administration has granted Fast Track designation for the investigation of radiotherapy-activated NBTXR3 in the NANORAY-312 population, which includes the opportunity for Priority Review and Accelerated Approval.

Tuba: Discuss the survival data of the study.

Laurent Levy: The primary endpoint of the pivotal study is Progression-free Survival (PFS) and secondary endpoints include Overall Survival (OS), response rates, and quality of life. A futility analysis is planned at 18 months and an interim readout at 30 months after the first randomized patient randomized.

Tuba: What geographical locations are you aiming for the study?

Laurent Levy: NANORAY-312 aims to enroll 500 patients across sites in the United States, Europe, and Asia. To date, 128 sites have been qualified in 29 countries.

Tuba: Discuss the safety and efficacy of NANORAY-312.

Laurent Levy: It is important to note that NANORAY-312 is the name of the study, while the drug being studied in this research is NBTXR3. Regarding NBTXR3, the NANORAY-312 study builds on Nanobiotix Study 102, a phase I trial evaluating the safety and early signs of efficacy for radiotherapy-activated NBTXR3 in high-risk elderly LA-HNSCC patients who are chemotherapy-ineligible and intolerant to cetuximab. Preliminary data presented at the 2021 Annual Meeting of the American Society for Radiation Oncology (ASTRO) showed that the treatment was feasible and well-tolerated at all dose levels. Exploratory efficacy data showed a high target lesion objective response rate of 85.4% and a target lesion complete response rate of 63.4%, along with a median PFS of 10.6 months and median OS of 18.1 months in the evaluable patient population.

Tuba: Are you planning for other products in the field of oncology (please mention the indications)?

Laurent Levy: The company’s resources are primarily devoted to the development of its lead product candidate NBTXR3, which is the product of its proprietary oncology platform and has already achieved market authorization in Europe for the treatment of patients with soft tissue sarcoma under the brand name Hensify. Given the physical mechanism of NBTXR3 is its activation by radiotherapy, the radio enhancer is being developed as both a solid tumor- and therapeutic combination-agnostic therapeutic candidate. To date, NBTXR3 has been injected in patients with soft tissue sarcoma, head and neck cancer, prostate cancer, liver cancer, non-small cell lung cancer, colorectal cancer, and pancreatic cancer. Moreover, radiotherapy-activated NBTXR3 is being evaluated in combination with nivolumab or pembrolizumab in order to improve treatment outcomes for IO naïve patients and in those whom prior anti-PD-1 treatment has failed. have failed previously anti-PD-1-containing treatment. NBTXR3 plus chemoradiation is also being evaluated in some trials.

Source: 1mg

About Author:

Laurent Levy is the Co-Founder of Nanobiotix and has served as CEO since March 2003. Laurent has extensive experience in sciences and techniques related to nanotechnologies. He holds a Doctorate in Physical Chemistry, specializing in nanomaterials, from the Pierre and Marie Curie University in Paris (Université Paris VI Pierre et Marie Curie) and from the CEA and a DEA (advanced studies and diplomas) in Physics of Condensed Matter from the UPVI-ESPCI. Laurent completed his studies with a post-doctoral fellowship at the Institute for Lasers, Photonics and Biophotonics at the State University of New York at Buffalo (SUNY Buffalo)

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