NBTXR3 With or Without Cetuximab in LA-HNSCC

Nanobiotix

Status and phase: Enrolling; Phase 3

Conditions: Aged; Locally Advanced Head and Neck Squamous Cell Carcinoma

Treatments: Radiation: Radiation Therapy; Drug: NBTXR3; Drug: Cetuximab

Study type: Interventional

Funder types: Industry

Identifiers

NCT04892173

NANORAY-312

Details and patient eligibility

About

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.

Full description

Participants will undergo a screening assessment over a period of ≤28 days to determine eligibility.

Eligible participants will be treated by the Investigator's choice of RT alone or RT in combination with cetuximab. Following the Investigator's choice, participants will be randomized in a 1:1 ratio:

• Arm A: NBTXR3, as an intratumoral/intranodal injection, activated by investigator's choice of RT alone or RT in combination with cetuximab
• Arm B: Investigator's choice of RT alone or RT in combination with cetuximab

All participants (Arm A and Arm B) will receive 70 Gy in 35 fractions over a 7 week period.

An EOT visit will be performed 4 weeks after the completion of RT. Follow-up visits will start at 12 weeks post-RT completion, and will continue every 12 weeks for 2 years, and then every 24 weeks thereafter until death; the participant is determined to be lost to follow up; withdrawal of consent; or the end of the study, whichever occurs first. Participants who have received further anti-cancer therapy for the study disease and/or have had disease progression/recurrence will be followed only for survival information

Enrollment: 500 estimated patients

Sex: All

Ages: 60+ years old

Volunteers: No Healthy Volunteers

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 ≥60 years

• Biopsy-confirmed squamous cell carcinoma (SCC) of the oral cavity, oropharynx, supraglottic larynx, 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 any N or T2, if ≥N2 according to the 8th edition of the American Joint Committee on Cancer Staging Manual (AJCC v8)

• Has one primary tumor lesion that is amenable for intratumoral injection, as determined by the Investigator

• 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 performance status=2
  5. New York Heart Association (NYHA) Class III OR Aged 70-74 with Geriatric 8 (G8) score ≤14 or aged ≥75 years

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

• Amenable to definitive treatment with RT. Participants 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.

• 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 x upper limit of normal (ULN)
  6. Aspartate aminotransferase (AST) ≤3×ULN
  7. Total bilirubin ≤1.5 ULN (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 if the participant is a candidate for cetuximab treatment as per the Investigator's choice prior to randomization
  9. Estimated creatinine clearance ≥30 mL/min (calculated by Cockcroft and Gault)

Exclusion criteria

• HNSCC category T1, T2N0, T2N1 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 and participants 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 participants can still be eligible for the study, only if RT alone is chosen by the Investigator before randomization)
• Known history of human immunodeficiency virus (HIV) Chronically ongoing active hepatitis B, or chronically ongoing active hepatitis C infection as defined in AASLD (American Association for the Study of Liver Diseases)/EASL (European Association for the Study of the Liver) guidelines
• Local regionally recurrent HNSCC that has been previously treated with surgery, chemotherapy and/or RT are not eligible for the study
• 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 (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
• 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 ≥1 year postmenopausal or surgically sterile is not considered to be of childbearing potential.
• 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, including subjects under legal protection
• Subject participating in another clinical study at the time of signature of the informed consent form
• Ongoing or active bacterial or fungal infection, symptomatic viral infection, any other clinically significant infection, or use of immune suppressive agents

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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500 participants in 2 patient groups

Arm A

Experimental group

Description:

NBTXR3, as an intratumoral/intranodal injection, activated by investigator's choice of RT alone or RT in combination with cetuximab. NBTXR3 is given as a single intratumoral injection as a dose of 33% of the Gross Tumor Volume

Treatment:

Drug: NBTXR3

Radiation: Radiation Therapy

Arm B

Active Comparator group

Description:

Investigator's choice of RT alone or RT in combination with cetuximab

Treatment:

Drug: Cetuximab

Radiation: Radiation Therapy