A Study of Debio 1143 (Xevinapant) in Combination With Platinum-Based Chemotherapy and Standard Fractionation Intensity-Modulated Radiotherapy in Participants With Locally Advanced Squamous Cell Carcinoma of the Head and Neck, Suitable for Definitive Chemoradiotherapy (TrilynX)

Open to people ages 18 years and up

• Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1
• Histologically confirmed diagnosis in previously untreated Locally Advanced Squamous Cell Carcinoma of the Head and Neck (LA-SCCHN) participant (stage III, IVa or IVb according to the American Joint Committee on Cancer(AJCC))/Classification of malignant tumors: T=size of the primary tumor, N=regional lymph node involvement, M=distant metastasis (TNM) Staging System, 8th Edition.) suitable for definitive

ChemoRadiotherapy (CRT), of at least one of the following sites: oropharynx, hypopharynx and larynx

• For OroPharyngeal Cancer (OPC) participants, primary tumors must be human papillomavirus (HPV)-negative as determined by p16 expression using immunohistochemistry
• Evaluable tumor burden (measurable and/or non-measurable tumor lesions) assessed by computed tomography scan (CT-scan) or magnetic resonance imaging (MRI), based on Response evaluation criteria in solid tumors (RECIST) version 1.1
• Peripheral neuropathy less than or equal to (<=) grade 2
• Adequate hematologic, renal and hepatic function
• Other protocol defined inclusion criteria may apply

• Primary tumor of nasopharyngeal, paranasal sinuses, nasal or oral cavity, salivary, thyroid or parathyroid gland pathologies, skin or unknown primary site
• Metastatic disease (stage IVc as per AJCC/TNM, 8th Ed.)
• Prior definitive or adjuvant Radiotherapy (RT) and/or radical surgery to the head and neck region which may jeopardize the primary tumor irradiation plan, or any other prior SCCHN systemic treatment, including investigational agents
• Documented weight loss of >10% during the last 4 weeks prior to randomization (unless adequate measures are undertaken for nutritional support), OR plasmatic albumin < 3.0 g/dL. No albumin transfusions are allowed within 2 weeks before randomization
• Known allergy to Debio 1143, cisplatin, carboplatin, other platinum-based agent or any excipient known to be present in any of these products or in the placebo formulation
• other protocol defined exclusion criteria may apply