NBTXR3 With or Without Cetuximab in LA-HNSCC

• Status: Not yet recruiting
• Trial end date: 2025-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a global, open-label, randomized, 2-arm, Investigator's choice Phase 3 (Pivotal Stage) study to investigate the efficacy/performance and safety of NBTXR3/RT±cetuximab versus RT±cetuximab in treatment-naïve, platinum-ineligible, elderly participants with LA-HNSCC.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Nanobiotix
• Treatments: Cetuximab

Criteria

Inclusion Criteria:

• Signed informed consent form (ICF) indicating that the participant understands the purpose of, and procedures required for the study, and is willing to participate in the study

• Age ≥65 years

• Biopsy-confirmed squamous cell carcinoma (SCC) of the oral cavity, oropharynx, or hypopharynx (archived biopsies are allowed); if no biopsies are available, a new biopsy must be obtained to provide confirmation of SCC

• For participants with oropharyngeal cancer, human papilloma virus (HPV) p16 status must be known

• Tumor categories T3-T4 according to the 8th edition of the American Joint Committee on Cancer Staging Manual (AJCC v8)

• Has at least 1 tumor lesion that can be accurately measured according to RECIST 1.1 (per the Central Imaging vendor) and is amenable for intratumoral injection, as determined by the Investigator

• A single invaded, biopsy confirmed, accessible LN in the neck of ≥3 cm and <10 cm and with <180-degree encasement of the carotid artery on MRI or CT scan is eligible for intranodal injection

• If a LN is selected for injection, 1 of the 2 injected lesions must be the primary tumor itself

• Ineligible to receive platinum-based chemotherapy for the treatment of LA HNSCC as defined by having at least one of the following:

1. Estimated creatinine clearance ≥30 and <50 mL/min (calculated by Cockcroft and Gault)

2. Hearing loss or tinnitus Grade ≥2

3. Grade ≥2 peripheral neuropathy

4. ECOG >2

5. Recent cardiac dysfunction (history of unstable angina pectoris, myocardial infarction, or New York Heart Association (NYHA) class III chronic heart failure <3 years prior to screening)

• Must be able to tolerate RT with curative intent as determined by the study Investigator.

• Not amenable to primary tumor surgery. Inability to undergo surgery must be determined by the treating physician in consultation with a head and neck surgeon, or if applicable, the site's multidisciplinary tumor board.

• ECOG performance status of 0 to 2

• Life expectancy ≥6 months

• Adequate organ and bone marrow function at screening as defined by:

1. Hemoglobin >9.0 g/dL

2. Platelet count >100,000 cells/mm3

3. Leukocytes >3000 cells/mm3

4. Absolute neutrophil count >1500 cells/mm3

5. Alanine aminotransferase (ALT) ≤3×upper limit of normal (ULN)

6. Aspartate aminotransferase (AST) ≤3×ULN

7. Total bilirubin ≤1.5 mg/dL (in participants with Gilbert's syndrome, if total bilirubin is >1.5×ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤1.5×ULN, the participant may be eligible)

8. Total serum magnesium within normal ranges (1.7-2.2 mg/dL or 0.85 to 1.10 mmol/L)

Exclusion Criteria:

• HNSCC category T1, T2 or M1 according to the 8th edition of the American Joint Committee on Cancer Staging Manual (AJCC v8)

• Has received prior antineoplastic systemic therapy or intervention (including pharmacological - both marketed and investigational, RT, or surgery) for the treatment of HNSCC

• Participants with known severe Grade 3 or 4 hypersensitivity reactions to cetuximab must be excluded from cetuximab treatment by the Investigator

• Known history of human immunodeficiency virus (HIV), active hepatitis B, or active hepatitis C infection

• Local regionally recurrent HNSCC

• Ulceration or other characteristics that may, in the opinion of the Investigator, increase the risk of severe tumor bleeding

• SCC originating in the nasopharynx or paranasal sinus, from the salivary gland, or thyroid gland, or non-squamous histology (e.g., melanoma or neuroendocrine carcinoma), or SCC of unknown primary origin

• Prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen

• Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes, second- or third-degree atrioventricular heart block without a permanent pacemaker in place)

• Class IV congestive heart failure as defined by the New York Heart Association functional classification system <6 months prior to screening

• A pregnant or nursing woman, or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception starting from signed ICF through 150 days after the last cetuximab dose/RT fraction. A woman who is 2 years postmenopausal or surgically sterile is not considered to be of childbearing potential.

• A known history of areca nut (betel nut) consumption

• Any condition for that, in the opinion of the Investigator, participation would not be in the best interest of the individual (e.g., compromises the participant's well-being) or that could prevent, limit, or confound the protocol/CIP specified assessments

• Subject participating in another clinical study at the time of signature of the informed consent form