A first patient in has been randomized in NANORAY-312, a global Phase 3 registration trial evaluating NBTXR3 (also known as PEP503) for the treatment of elderly patients with locally advanced head and neck squamous cell carcinoma (“LA-HNSCC”) who are ineligible for platinum-based chemotherapy.
Today, the majority of head and neck cancers are derived from the mucosal epithelium in the oral cavity, pharynx and larynx. Collectively they are known as head and neck squamous cell carcinoma (HNSCC). And while oral cavity and larynx cancers are generally associated with tobacco consumption, alcohol abuse or both, cancers of the pharynx cancers are increasingly attributed to infection with human papillomavirus (HPV). 
Surgery and radiotherapy are considered the baseline treatment options for most initial stage HNSCC patients, but these treatments are associated with significant morbidity and poor prognosis. Hence, there is a major unmet medical need requiring novel treatment options. 
The investigational agent, a hafnium oxide (HfO2) nanoparticle NBTXR3, being developed by Nanobiotix, is activated by radiotherapy and will be evaluated alone or in combination with cetuximab and is a potentially first-in-class radioenhancer with broad application across solid tumors, with prioritized focus in head and neck cancer.
In this study, eligible participants will be treated with NBTXR3 at a 1:1 ratio after an Investigator’s Choice of radiotherapy alone or radiotherapy in combination with cetuximab (Erbitux®; Eli Lilly and Company).
Earlier studies with NBTXR3 investigated the drug candidate activated by radiotherapy versus radiotherapy alone as a pre-operative treatment in patients with locally advanced soft-tissue sarcoma.These studies validated the mode of action of this new class of radioenhancer, potentially opens a large field of clinical applications in soft-tissue sarcoma and possibly other cancers.
Other studies confirmed that NBTXR3 was internalized by cancer cells and persisted within the tumors throughout radiotherapy treatment. When activated by radiotherapy, NBTXR3 was also more effective in killing cancer cells and in controlling tumor growth than radiotherapy alone. Furthermore, beyond the effects of NBTXR3 as single agent, studies have shown that the antitumor efficacy of cisplatin-based chemoradiotherapy treatment was improved when combined with NBTXR3.
NBTXR3 is composed of functionalized hafnium oxide nanoparticles that is 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 adaptive immune response and long-term anti-cancer memory. Given the physical MoA, researchers involved in the development of the agent believe that NBTXR3 could be scalable across any solid tumor that can be treated with radiotherapy and across any therapeutic combination, particularly immune checkpoint inhibitors.
“Our pivotal, global Phase 3 NANORAY-312 trial for lead candidate NBTXR3 continues to build momentum with sites now active in the United States, Europe and Asia,” said Laurent Levy, co-founder of Nanobiotix and chairman of the executive board.
“NANORAY-312 is the first of our prioritized registrational trials in head and neck cancer and is designed to prove that our innovation can make a difference for elderly patients around the world, a growing patient population with high unmet medical need. We believe data on survival and anti-tumoral response in our proof-of-concept Phase 1 Study 102 continue to support the potential of NBTXR3 as a single agent activated by radiotherapy for the treatment of elderly patients with head and neck cancer and we look forward to reporting additional milestones from our head and neck cancer franchise studies in 2023.”
The first patient in NANORAY-312 was randomized in Europe by Nanobiotix in January of 2022, followed by randomization of the first patient in Asia by Nanobiotix’ strategic collaborator LianBio in August of 2022. The addition of the first patient in the United States completes the Company’s planned study initiation milestones in 2022. Nanobiotix remains focused on expanding the trial’s site footprint, building on the 80 sites currently activated; driving patient recruitment; and preparing for planned milestone reporting in 2023.
NANORAY-312 is being conducted in partnership with LianBio. LianBio is leading clinical development in Asia and holds exclusive rights to develop and commercialize NBTXR3 in Greater China, South Korea, Singapore and Thailand. Nanobiotix is leading clinical and commercial development in all other regions.
NBTXR3 With or Without Cetuximab in LA-HNSCC – NCT04892173
NBTXR3, Radiation Therapy, and Pembrolizumab for the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Cancer – NCT04862455
NBTXR3 Crystalline Nanoparticles and Radiation Therapy in Treating Patients With Soft Tissue Sarcoma of the Extremity – NCT01433068
NBTXR3 and Radiation Therapy in Treating Patients With Locally Advanced SCC of the Oral Cavity or Oropharynx – NCT01946867
Re-irradiation With NBTXR3 in Combination With Pembrolizumab for the Treatment of Inoperable Locoregional Recurrent Head and Neck Squamous Cell Cancer – NCT04834349
Highlights of Prescribing information
Cetuximab (Erbitux®; Eli Lilly and Company) [Prescribing Information]
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Featured image: The hands of two radiation therapists are shown fitting a short face mask to a patient model to steady the head during radiation therapy. Photo courtesy: © 2010 National Cancer Institute on Unsplash Used with permission.