• Age ≥ 18 years old on the day of signing the informed consent.

• Diagnosis of histologically proven recurrent or metastatic squamous cell carcinoma of the head and neck not accessible to treatment with curative intent.

• Patients must not have received previous systemic therapy administered in the context of recurrent or metastatic disease.

• If the patient received chemotherapy with a platinum salt as part of multimodal treatment for locally advanced disease, it must have ended at least 6 months before signing the consent.

• Eligible primary tumor locations are the oropharynx, oral cavity, hypopharynx and larynx. Subjects cannot have a primary tumor site (any histology) in the nasopharynx, sinuses, nasal cavity, salivary glands, or skin.

• Documented Combined Positive Score (CPS) PD-L1 ≥ 1 (determined according to local practices in each center) Note: the CPS score can be performed on a new biopsy or on an archived tumor specimen, without date limitation.

• Have measurable disease on CT-scan (or on MRI of the neck if it provides a better measurement of the primary tumor according to standard practice and the investigator judgement) according to RECIST 1.1 as determined by the investigator. Tumor lesions located in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. Note : In case of neck MRI assessment, the chest, abdominal, and pelvic CT scan must be performed in addition to assess potential metastases.

• Have a performance status of 0 or 1 on the ECOG performance scale.

• Demonstrate adequate organ function as defined in the protocol.

⁃ Have HPV status test results for oropharyngeal cancers defined as a p16 immunohistochemical (IHC) test (determined according to local practices in each center).

⁃ Note: Cancers of the oral cavity, hypopharynx, and larynx are not required to perform HPV testing by p16 IHC because, by convention, these tumor locations are assumed to be HPV negative.

⁃ Female subjects of childbearing potential must have a negative pregnancy test within 72 hours prior to receiving the first dose of study treatment.

⁃ Female subjects of childbearing potential must be willing to follow at least one method of contraception or be surgically sterile, or abstain from heterosexual activity for the duration of the study and until 4 months for pembrolizumab, 6 months for carboplatin and 5-fluorouracil, and 7,5 months for cisplatin after the last dose of study treatment respectively for each molecule. Subjects of childbearing potential are those who have not been surgically sterilized and who had menstruation in the last 12 months.

⁃ Note: Abstinence is acceptable if it is the subject's usual lifestyle and preferred method of contraception.

⁃ Male subjects must agree to use at least one method of contraception for the duration of the study and until 180 days after the last dose of study treatment.

⁃ Note: Abstinence is acceptable if it is the subject's usual lifestyle and preferred method of contraception.

⁃ Signed written informed consent

⁃ Patient able to participate and willing to give informed consent prior performance of any study-related procedures and to comply with the study protocol

⁃ Patient affiliated to a Social Health Insurance in France