Study of Pembrolizumab as First Line Therapy in Patients With Unresectable Squamous Cell Carcinoma of the Skin

Inclusion Criteria: * Be willing and able to provide written informed consent/assent for the trial * Be more than 18 years of age on day of signing informed consent. * Be either affiliated to, or a beneficiary of, a social security category * Have metastatic disease, or locally advanced disease not amenable to surgery with documented progression * Be willing and able to undergo pre-treatment baseline biopsy of the tumor * PD-L1+ or PD-L1- tumors * Have measurable disease based on RECIST 1.1 * Have a performance status of 0 or 1 on the Easter Cooperative Oncology Group (ECOG) Performance Scale. * Demonstrate adequate organ function as defined in Table 3, all screening labs should be performed within 10 days of treatment initiation. * Have recovered from major surgery or radiation therapy * Female subject of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. * Female subjects of childbearing potential should be willing to use 1 method of birth control before the first dose of study therapy through 120 days after the last dose of study therapy. (Reference Section 7.5.1). Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy. Exclusion Criteria: * Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks or 5 half-lives (minimum 14 days), whichever is shorter, prior to the first dose of treatment. * Has received prior therapy with either chemotherapy or targeted therapy for the present tumor * Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent. * Has received radiation therapy within 4 weeks prior to study Day 1 * Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. * Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. * Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies) * Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., Hepatitis C Virus RNA \[qualitative\] is detected). * Has known history of, or any evidence of active, non-infectious pneumonitis. * Has an active infection requiring systemic therapy * Has received a live vaccine within 30 days of planned start of study therapy. * Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Fluenz tetra®) are live attenuated vaccines, and are not allowed. * Hypersensitivity to pembrolizumab or any of its excipients. * Has a known additional malignancy. Exceptions include i) basal cell carcinoma of the skin or other squamous cell carcinoma of the skin or in situ cervical cancer, ii) history of another non blood malignancy that has undergone potentially curative therapy without recurrence for more than 2 years. * Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with brain metastases may participate provided they are stable (without evidence of progression by imaging for at least eight weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability. * Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. * Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. * Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.