FDA Accepts Protocol Amendment to Phase 3 NANORAY-312 Trial in HNSCC

The FDA has accepted an amendment to the protocol of the phase 3 NANORAY-312 trial (NCT04892173) evaluating JNJ-1900 (NBTXR3) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC), according to a news release from the developer, Nanobiotix.¹

Specifically, the protocol amendment removed the previously planned interim analysis and modifies the readout of the final analysis to include fewer events, with the analysis being conducted sooner. According to the developers, this decision could accelerate and expand the global registration pathway for the agent in this HNSCC population. Moreover, they anticipate that the final analysis should occur in a similar timeframe as the previously planned interim analysis. However, the timing will be dependent on when the clinical events threshold is met.

The study is currently evaluating the efficacy of JNJ-1900 compared with standard-of-care therapy for this HNSCC group. Patients enrolled on the study were randomly assigned 1:1 to receive JNJ-1900 or placebo with radiotherapy with or without cetuximab (Erbitux).² Those who were 60 years and older with biopsy-confirmed SCC of the oral cavity, oropharynx, hypopharynx, or supraglottic larynx, and T3 to 4 and N or T2 and N2 or greater disease per American Joint Committee on Cancer tumor-node-metastasis staging classification of malignant tumors v8 (AJCC TNM v8) were eligible for trial enrollment.

Those who were treated received investigator’s choice of radiotherapy alone or in combination with cetuximab, with receipt of investigational treatment occurring the following day. JNJ-1900 was given under local or general anesthetic as an intratumoral or intranodal injection at a dose level of 33% of the gross tumor volume. Following the injection, the patient was closely monitored. Radiotherapy was given at 70 Gy of intensity-modulated radiation therapy (IMRT) across 35 fractions over approximately 7 weeks; cetuximab was given at 400 mg/m² over 120 minutes of body surface area at 1 week prior to start of radiation, followed by 250 mg/m² over 60 minutes weekly for the duration of radiotherapy treatment.

The primary end point of the trial is progression-free survival (PFS) per central imaging assessments. Overall survival is a key secondary end point, with time to locoregional progression, time to distant progression, HNC-specific event-free survival and HNC-specific survival all being additional secondary end points.

“Cisplatin-ineligible [older] patients with LA-HNSCC have limited therapeutic options, underscoring the high unmet need for effective treatments. The NANORAY-312 approach of combining the radioenhancer [JNJ-1900] with [radiotherapy with or without] cetuximab holds promise for improving treatment outcomes in this patient population, and results from this study are eagerly awaited,” Christophe Le Tourneau, MD, PhD, head of the Department of Drug Development and Innovation (D3i) and the Head and Neck Clinic, as well as a senior medical oncologist at the Institut Curie and full professor of Medicine at Paris-Saclay University, wrote in a publication of the phase 3 protocol with study coinvestigators.²

JNJ-1900 was developed as a potentially first-in-class oncology product containing radiation-activated functionalized hafnium oxide nanoparticles administered via a single intratumoral injection. The mechanism of action is intended to induce tumor cell death in the injection lesion when activated by radiotherapy, triggering an adaptive immune response and long-term anti-cancer memory. According to the developers, this product could be scalable across any solid tumor that can be managed with radiotherapy given the physical mechanism of action, with potential use in therapeutic combinations including immune checkpoint inhibition.

References

1. Nanobiotix announces protocol amendment to ongoing global phase 3 head and neck cancer study. News release. Nanobiotix. May 4, 2026. Accessed May 5, 2026. https://tinyurl.com/4p7rx5ej
2. Le Tourneau C, Takácsi-Nagy Z, Nuyts S, et al. Nanoray-312: phase III study of NBTXR3 + radiotherapy ± cetuximab in elderly, platinum-ineligible locally advanced HNSCC. Future Oncol. 2025;21(12):1489-1499. doi:10.1080/14796694.2025.2496131