Pembrolizumab and Radiotherapy for Oligometastatic Head and Neck Cancer

Main inclusion Criteria: * Male/female participants who are at least 18 years of age on the day of signing informed consent * Histologically confirmed HNSCC of the oral cavity, oropharynx, hypopharynx, larynx or cervical primary occult and histologically or radiologically confirmed oligometastatic disease. Histological characterization of one metastatic lesion is strongly recommended. * Patients with synchronous or metachronous oligometastatic disease according to the ESTRO/EORTC consensus (1-5 metastatic lesions, with or without primary/recurrent primary tumour and/or regional disease). * Amenable to first-line systemic treatment for R/M SCCHN. * For patients with oropharyngeal cancer: HPV status using p16 IHC evaluated locally. * PD-L1 CPS of at least 1 as evaluated locally. * Staging not older than 12 weeks before enrolment. * All the 1-5 metastases must be amenable to SABR. * Eligible for treatment with pembrolizumab. * Have measurable disease based on RECIST 1.1. * ECOG performance status of 0 to 1. * Participants must have recovered from all treatment-related toxicities to baseline or grade ≤1, such as from previous radiotherapy, systemic treatment or surgery, and not requiring corticosteroids for managing treatment-related side effects. * Adequate Organ Function Laboratory Values. * Before patient registration/enrolment, written informed consent must be given according to ICH/GCP, and national/local regulations. Main exclusion Criteria: * Nasopharynx, sino-nasal, and salivary gland cancers are excluded. * In-field progression in \< 6 months after curative intended locoregional irradiation of the head and neck. * Lesions larger than 6 cm in the largest dimension as measured in the diagnostic CT or MRI scan for lesions outside the brain. Note: bone metastases over 6 cm may be included if in the opinion of the local radiation oncologist they can be treated safely and no inner organ is affected. * Brain metastases only. * Has received any previous radiotherapy to any of the 1-5 metastases that would be subject to SABR in the experimental arm unless the investigator agrees to treat only after discussion with the RTQA team. * Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention. * Previously treated brain metastases that are radiologically non-stable. Patients with previously treated brain metastases, i.e., without evidence of progression for at least 4 weeks by repeat imaging, clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention, can participate. * Known contraindication to imaging tracer or any product of contrast media and MRI contraindications.