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 therapywith 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 ofthe 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 (<=) 14or 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; ornon-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 withsurgery, radiation therapy, and/or chemotherapy

• Prior or concurrent primary malignancy (including second synchronous head & neckcancer) within the last 2 years of informed consent and whose natural history hasthe potential to interfere with the safety and efficacy assessment of theinvestigational agent

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