JNJ-90301900 (NBTXR3) Activated by Radiotherapy With or Without Cetuximab in LA-HNSCC

Inclusion Criteria:

- Age greater than or equal to (>=) 60 years old

- Squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or supraglottic larynx and a candidate for definitive radiation therapy with or without cetuximab

- Clinical stage T3-4 NX or T2 N2-3 disease according to the 8th edition of AJCC

- One primary tumor lesion amendable for intratumoral injection

- Ineligible to receive platinum-based chemotherapy with radiation (at least one of the following):

1. Estimated creatinine clearance >= 30 and less than (<) 50 milliliters/minute (mL/min) (per Cockcroft-Gault equation), Grade >= 2 hearing loss or tinnitus, Grade >= 2 peripheral neuropathy, Eastern Cooperative Oncology Group (ECOG) Performance Status 2 or New York Heart Association Class 3

2. Age 70-74 years old with Geriatric 8 (G8) score less than or equal to (<=) 14

3. Age >= 75 years old

Exclusion Criteria:

- Carcinoma of the nasopharynx, paranasal sinus(es), salivary gland, thyroid gland, or unknown primary

- Non-squamous cell histology

- Clinical stage T1-2 N0, T2 N1, or M1 disease according to the 8th edition of AJCC

- Loco-regionally recurrent head & neck cancer that has been previously treated with surgery, radiation therapy, and/or chemotherapy

- Prior or concurrent primary malignancy (including second synchronous head & neck cancer) within the last 2 years of informed consent and whose natural history has the potential to interfere with the safety and efficacy assessment of the investigational agent

- Ongoing or active infection requiring treatment with antimicrobial therapy within 2 weeks of randomization