A Phase 3 (Pivotal Stage) Study of NBTXR3 Activated by Investigator’s Choice of Radiotherapy Alone or Radiotherapy in Combination with Cetuximab for platinum-based Chemotherapy-ineligible Elderly Patients with Locally Advanced Head & Neck Squamous Cell Carcinoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Nanobiotix

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

26 Apr 2022 → 14 Jan 2026

Decision date (initial)

2024-11-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Nanobiotix SA

External identifiers

EU CT number

2024-513082-39-00

EudraCT number

2021-002163-22

ClinicalTrials.gov

NCT04892173

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Therapy, Efficacy

To evaluate survival outcomes in subjects treated with intratumorally injected NBTXR3 activated by investigator's choice of RT alone or RT in combination with cetuximab in comparison to Investigator's choice alone hereafter referred to as NBTXR3/RT±cetuximab versus RT±cetuximab

Secondary objectives 1

1. To evaluate long-term survival outcomes of NBTXR3/RT±cetuximab versus RT±cetuximab

Conditions and MedDRA coding

Locally Advanced Head & Neck Squamous Cell Carcinoma

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. 1. Signed informed consent form (ICF) indicating that the subject understands the purpose of, and procedures required for the study, and is willing to participate in the study
2. 2. Age ≥60 years
3. 3. Biopsy-confirmed SCC of the oral cavity, oropharynx, hypopharynx or supraglottic larynx (archived biopsies are allowed); if no biopsies are available, a new biopsy must be obtained to provide confirmation of SCC
4. 4. For subjects with oropharyngeal cancer, HPV status must be known
5. 5. Tumor categories T3-T4 any N or T2, if ≥N2 according to the 8th Edition of the AJCC Cancer Staging Manual
6. 6. Has one primary tumor lesion that is amenable for intratumoral injection, as determined by the Investigator
7. 7. Ineligible to receive platinum-based chemotherapy for the treatment of LA HNSCC as defined by having at least one of the following: a. Estimated creatinine clearance ≥30 and <50 mL/min (calculated by Cockcroft and Gault) b. Hearing loss or tinnitus Grade ≥2 c. Grade ≥2 peripheral neuropathy d. ECOG performance status=2 e. New York Heart Association (NYHA) Class III OR Aged 70-74 with Geriatric 8 (G8) score ≤14 or aged ≥75 years
8. 8. Must be able to tolerate RT with curative intent as determined by the study Investigator.
9. 9. Amenable to definitive treatment with RT. Subjects with an oral cavity cancer should not be eligible to the primary standard treatment, which is surgery, and the decision for definitive treatment with RT requires consultation with the head and neck surgeon, and the site's multidisciplinary tumor board.
10. 10. ECOG performance status of 0 to ≤2
11. 11. Life expectancy ≥6 months
12. 12. Adequate organ and bone marrow function at screening as defined by: a. Hemoglobin >9.0 g/dL b. Platelet count ≥100,000 cells/mm3 c. Leukocytes >3000 cells/mm3 d. Absolute neutrophil count >1500 cells/mm3 e. Alanine aminotransferase (ALT) ≤3×upper limit of normal (ULN) f. Aspartate aminotransferase (AST) ≤3×ULN g. Total bilirubin ≤1.5 ULN (in subjects 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 subject may be eligible) h. Total serum magnesium within normal ranges if the subject is a candidate for cetuximab treatment as per the Investigator's choice prior to randomization. i. Estimated creatinine clearance ≥30 mL/min (calculated by Cockcroft and Gault)

Exclusion criteria 14

1. 1. HNSCC category T1, T2 N0, T2 N1, or M1 according to the 8th Edition of AJCC Cancer Staging Manual.
2. 2. Has received prior antineoplastic systemic therapy or intervention (including pharmacological - both marketed and investigational, RT, or surgery) for the treatment of HNSCC
3. 3. Subjects with known severe Grade 3 or 4 hypersensitivity reactions to cetuximab and subjects with known prior or ongoing interstitial lung disease must be excluded as a candidate for cetuximab treatment as per the Investigator's choice before randomization (these subjects can still be eligible for the study, only if RT alone or NBTXR3+RT alone is chosen and documented by the Investigator before randomization)
4. 4. Known history of HIV, Chronically ongoing active hepatitis B, or chronically ongoing active hepatitis C infection as defined in AASLD/EASL guidelines
5. 5. Loco-regionally recurrent HNSCC that has been previously treated with surgery, chemotherapy and/ or RT are not eligible for the study.5. Loco-regionally recurrent HNSCC that has been previously treated with surgery, chemotherapy and/ or RT are not eligible for the study.
6. 6. Ulceration or other characteristics (e.g. bleeding diathesis) that may, in the opinion of the Investigator, increase the risk of severe tumor bleeding
7. 7. SCC originating in the nasopharynx, paranasal sinus, salivary gland, or thyroid gland; non-squamous histology (e.g., melanoma or neuroendocrine carcinoma), or SCC of unknown primary origin
8. 8. Prior or concurrent malignancy (including a second synchronous HNSCC) whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen except when: • The risk of the prior malignancy interfering with either safety or efficacy endpoints is very low; and if all treatment of that malignancy was completed at least 2 years before randomization and the subject has no clinical evidence of disease recurrence • This exception includes completely resected/treated non-melanoma skin cancer, cervical uterine cancer, T1 N0 M0 invasive hormone-sensitive breast cancer, hormone- sensitive prostate cancer with a Gleason score of 6, and completely resected non muscle invasive bladder cancer
9. 9. 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)
10. 10. Class IV congestive heart failure as defined by the NYHA functional classification system <6 months prior to screening
11. 11. 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 the time that the ICF is signed through 150 days (18 months for South Korean subjects) after the last cetuximab dose/RT fraction. A woman who is ≥ 1 year postmenopausal or who is surgically sterile is not considered to be of childbearing potential (pregnancy test is not required).
12. 12. 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 subject's well-being) or that could prevent, limit, or confound the protocol/CIP specified assessments, including subjects under legal protection.
13. 13. Ongoing or active bacterial or fungal infection (includes infection requiring treatment with antimicrobial therapy for which participants will be required to complete 2 weeks before randomization), symptomatic viral infection, any other clinically significant infection, or use of immune suppressive agents.
14. 14. Subject participating in another clinical study, except for a non interventional trial/registry at the time of signing the ICF

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. PFS: time from randomization to loco-regional recurrence, loco-regional progression, distant progression, or death from any cause, whichever occurs first

Secondary endpoints 1

1. OS: time from randomization to death from any cause

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Nanobiotix

Sponsor organisation

Nanobiotix

Address

60 Rue De Wattignies

City

Paris

Postcode

75012

Country

France

Scientific contact point

Organisation

Nanobiotix

Contact name

NANORAY-CST

Public contact point

Organisation

Nanobiotix

Contact name

NANORAY-CST

Third parties 12

Locations

3 EU/EEA countries · 10 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 20 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications