Radiotherapy-Activated NBTXR3 Elicits Activity in Older/Comorbid Locally Advanced HNSCC

Treatment with the first-in-class radioenhancer NBTXR3 proved tolerable and effective in older patients with advanced head and neck squamous cell carcinoma (HNSCC) and a comorbidity index, according to final data from the phase 1 dose-expansion cohort of Study 102 (NCT01946867).^1,2

Among evaluable patients (n = 44) at a median follow-up of 18.2 months, the injected-lesion overall response rate (ORR) was 81.8% (n = 36) per RECIST v1.1 criteria, with a complete response (CR) rate of 63.6% (n = 28). Median duration of response in the target lesion was not reached, median progression-free survival was 16.9 months per independent review committee assessment, and median overall survival was 23.1 months. In all lesions, the ORR was 79.5% (n = 23) with a CR rate of 52.3% (n = 23).

“The hypothesis we sought to evaluate in Study 102 was that novel radioenhancer NBTXR3—as a single intratumoral injection procedure, that does not interact directly with other drugs, and could potentially improve locoregional control of the primary tumor without adding harmful side effects for elderly patients with head and neck cancer—may provide a promising new therapeutic option,” Christophe Le Tourneau, MD, principal investigator for Study 102, stated in a news release. “The favorable safety profile we have seen throughout the study, along with what we believe is meaningful efficacy, reinforce my confidence in the potential of NBTXR3 for these patients.”

Standard therapy for patients with locally advanced HNSCC includes surgery or definitive cisplatin-based chemotherapy. However, approximately 30% of patients are unfit for cisplatin because of frailty or comorbidities. As such, new therapies that provide improved tolerability and local control are needed for this population.

Study 102 is a multicenter, phase 1 dose-escalation and dose-expansion study. Previously, investigators confirmed safety without any dose-limiting toxicities at a recommended phase 2 dose of 22% of tumor volume. A total of 56 patients were enrolled and treated in dose expansion with a single injection of NBTXR3 to their primary lesion. All lesions were subsequently treated with the same dose of intensity-modulated radiation therapy (IMRT). 

Enrolled patients had negative prognostic factors including advanced age (≥70 years, 61%) and an age-adjusted Charlson Comorbidity Index (ACCI) of at least 4 (ACCI 4, 67%).

Regarding safety, all 56 patients were treated with at least 90% of the planned injected volume of NBTXR3. Five patients discontinued IMRT because of treatment-emergent adverse effects, resulting in a 91% completion rate. A total of 10 deaths occurred within 180 days of enrollment, one of which was deemed possibly related to treatment.

“Underlying the NBTXR3 global development program is the belief that the universal, physics-based mechanism of our potential first-in-class radioenhancer could significantly increase the dose of radiotherapy within the injected tumor without increasing harmful side effects for patients with cancer,” Louis Kayitalire, MD, chief medical officer at Nanobiotix, said in a news release. “In my view, the results from Study 102 could represent a significant step toward validating this hypothesis and addressing the unmet needs of patients with head and neck cancer. The signals of safety and efficacy we observed in Study 102, combined with the learnings we have applied in the design of our pivotal Phase 3 study in a similar population, add to my conviction that NBTXR3 has the potential to revolutionize treatment for millions of patients with cancer around the world.”

The ongoing, phase 3 NANORAY-312 trial (NCT04892173) is now open, evaluating NBTXR3 with or without cetuximab (Erbitux) in elderly patients with locally advanced HNSCC. Primary interim results from the trial are expected by mid-2025.^1,3

References

1. Nanobiotix announces the presentation of the final efficacy analysis from phase 1 cohort expansion evaluating NBTXR3 in locally advanced head and neck cancer showing median progression-free survival of 16.9 months and median overall survival of 23.1 months. News release. Nanobiotix. October 4, 2023. Accessed October 6, 2023. https://finance.yahoo.com/news
2. NBTXR3 and radiation therapy in treating patients with locally advanced SCC of the oral cavity or oropharynx. ClinicalTrials.gov. Updated December 29, 2022. Accessed October 6, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT01946867
3. NBTXR3 with or without cetuximab in LA-HNSCC. ClinicalTrials.gov. Updated January 3, 2023. Accessed October 6, 2023. https://clinicaltrials.gov/study/NCT04892173