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

Inclusion Criteria:

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

* Biopsy-confirmed 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),

2. Grade >= 2 hearing loss or tinnitus,

3. Grade >= 2 peripheral neuropathy,

4. New York Heart Association Class 3

5. Aged 70-74 years old with Geriatric 8 (G8) score less than or equal to (<=) 14 or Aged >= 75 years old

* Eastern cooperative oncology group (ECOG) performance status 0 to 1

* Life expectancy >= 6 months

Exclusion Criteria:

* Carcinoma of the nasopharynx, paranasal sinus, salivary gland, or thyroid gland; or non-squamous histology or SCC of unknown primary origin

* 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