Results on Dose Expansion for R3 Combined with RT for Cisplatin-Ineligible LA HNSCC Patients

Presenting author:
Christophe Le Tourneau, MD, PhD

By Jonathan D. Schoenfeld MD, MPH, Dana-Farber Brigham Cancer Center

Chemoradiation with concurrent cisplatin is standard treatment for patients with locally advanced head and neck squamous cell cancer (LA HNSCC). However, many patients are not candidates for cisplatin; treatment options for these patients are limited. Christophe Le Tourneau, MD, PhD, and colleagues presented favorable results from a phase I trial investigating a nanoparticle radioenhancer NBTXR3 (R3) combined with radiation as a potential new option for these cisplatin-ineligible LA HNSCC patients demonstrating feasibility and local response.

Background: R3 are hafnium oxide nanoparticles administered via one-time intratumoral injection that amplifies radiation induced tumor cell death. In the trial presented yesterday during the K. Kian Ang, MD, PhD, FASTRO, Commemorative Plenary Session, R3 was evaluated in LA HNSCC patients ineligible for cisplatin-radiation. As many as one-third of LA HNSCC patients may be cisplatin ineligible for reasons including advanced age or comorbidities. Treatment options for these patients include radiation monotherapy, or use of an alternative systemic agent such as the EGFR-targeting antibody cetuximab, or docetaxel, among others. Outcomes are poor, particularly for patients with disease that is not HPV associated.

Trial design: This multicenter phase I trial enrolled patients with LA HNSCC (T3, T4 or stage III/IVA) age >=70, or >=65 with cisplatin contraindication and primary tumors amenable to local R3 injection. Following R3 injection, 70 Gy of IMRT was administered in 35 fractions over a period of seven weeks. In the previously reported dose escalation, the amount of R3 injected was escalated to the recommended dose of 22% of the theoretical volume of the injected tumor. In yesterday’s session, the authors reported results from the dose expansion portion of the study. Primary objectives were to determine safety and a preliminary estimate of efficacy.

Study outcomes: 56 patients were treated from 2019-2022 across 20 sites. Median patient age was 72 and most had multiple comorbidities with age-adjusted comorbidity index >=4 in 67%. The majority (80%) also had T3-4 disease. Primary tumor sites included the oropharynx in 55% (45% of these p16+) and oral cavity in 45%. All patients received at least 90% of the planned R3 injection volume and IMRT was completed in 91%. Treatment emergent adverse events (TEAE) grade >=3 related to R3 were observed in 11%. Among 44 evaluable patients, 64% had a complete response of the injected lesion, and another 18% had a partial response. Median duration of injected lesion response was not reached and median PFS was 11.4 months.

Takeaways and future direction: This phase I dose expansion cohort demonstrates R3 injection is feasible in an elderly population with significant comorbidities, 91% of whom tolerated full dose radiation. The overall response rate of almost 80% in the injected lesions supports an ongoing randomized phase III NANORAY-312 study. According to Dr. Le Tourneau, “If these encouraging results are confirmed in the ongoing randomized phase III trial, the R3 radioenhancer will become a new treatment option for patients with LA-HNSCC who are not eligible for cisplatin-RT.”  More broadly, these results support further investigation of novel radiosensitizing approaches to improve outcomes for LA HNSCC patients.

Abstract 7, Novel Radioenhancer NBTXR3 Activated by Radiotherapy in Cisplatin-Ineligible Locally Advanced HNSCC Patients: Final and Exploratory Results of a Phase I Trial, was presented during the K. Kian Ang, MD, PhD, FASTRO, Commemorative Plenary Session at the 2024 Multidisciplinary Head and Neck Cancers Symposium on February 29, 2024.




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