This clinical trial is focused on studying a type of cancer called Locally Advanced Head and Neck Squamous Cell Carcinoma. This is a condition where cancer cells form in the tissues of the head and neck area. The study is testing a treatment involving a substance called JNJ-90301900, also known as NBTXR3, which is injected directly into the tumor. This treatment is being tested with or without the use of another medication called cetuximab, which is given through an infusion into a vein. The purpose of the study is to evaluate how well these treatments work in improving survival outcomes for patients who cannot receive a common chemotherapy treatment based on platinum.

Participants in the study will receive either the NBTXR3 treatment activated by radiotherapy, with or without cetuximab, or they will receive radiotherapy with or without cetuximab alone. Radiotherapy is a treatment that uses high doses of radiation to kill cancer cells and shrink tumors. The study will compare the outcomes of these different treatment options to see which is more effective in preventing the cancer from coming back or spreading.

The study will follow participants over a period of time to monitor their health and the progression of their cancer. The main goal is to see how long patients live without the cancer getting worse, which is known as progression-free survival. This information will help doctors understand the best treatment options for patients with this type of cancer who are not able to undergo standard chemotherapy treatments.