Phase III Xevinapant (Debio 1143) and Radiotherapy in Resected LA SCCHN, High Risk, Cisplatin-ineligible Participants (XRAY VISION)

Inclusion Criteria: * Participants with Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-2 and able to tolerate standard of care IMRT treatment according to Investigator assessment * Participants with histologically confirmed squamous cell carcinoma with one of the following primary sites: oral cavity, oropharynx, hypopharynx or larynx. Participants have received surgery with curative intent on these sites in the past 4 to 10 weeks before start of treatment (Cycle 1 Day 1) * Oropharynx (OPC) participants must have known human papillomavirus (HPV) status as determined by p16 expression using immunohistochemistry (ICH) * Participants with no residual disease by computed tomography (CT) or magnetic resonance imaging (MRI) and have a high risk of relapse with 1 or 2 of the following criteria, confirmed by local histopathology: • nodal extra-capsular extension (ECE) and positive resection margins (R1 or close margin less than or equal to (\<=) 1 millimeter (mm) * Are unfit to receive high-dose cisplatin by meeting one or more of the following criteria: estimated glomerular filtration rate (eGFR) \< 60 milliliter per minute per 1.73 meter square (mL/min /1.73 m\^2); History of hearing impairment, defined as Grade \>= 2 audiometric hearing loss or tinnitus Grade \>= 2. An audiogram is not required if one of the other criteria meets unfitness to receive high-dose cisplatin; Peripheral neuropathy \> = Grade 2 and if \>= 70 years, unfit according to G8 questionnaire (Score \<= 14) or ineligible for cisplatin treatment due to age limit according to national guidelines * Participants with adequate renal, hematologic and hepatic function as defined in the protocol * Other protocol-defined inclusion criteria could apply Exclusion Criteria: * Any condition, including any uncontrolled disease state other than SCCHN that in the Investigator's opinion constitutes an inappropriate risk or a contraindication for participation in the study or that could interfere with the study objectives, conduct, or evaluation * Participants with incomplete surgery * Participants with recurrent or metastatic disease * Primary tumor of nasopharyngeal, paranasal sinuses, nasal cavity, salivary, thyroid or parathyroid gland, skin or unknown primary site * Prior definitive, neoadjuvant, concurrent or adjuvant (C)RT to the head and neck region which may jeopardize the primary tumor irradiation plan, or any other prior SCCHN systemic treatment, including investigational agents * Participation in any interventional clinical study within 28 days prior to screening or during participation in this study * Known contraindication to undergoing positron emission tomography with 18F-FDG-PET-CT scans, or both contrast-enhanced MRI and contrast-enhanced CT scans * Known allergy to Xevinapant (Debio 1143) or any excipient known to be present in Xevinapant (Debio 1143) or in the placebo formulation * Other protocol-defined exclusion criteria could apply