Immunotherapy +/- EGFR Inhibitor In Advanced/Metastatic cSCC: Tackling Primary And Secondary Resistance

Inclusion Criteria:

* Willing and able to provide written informed consent/assent for the trial.
* 18 years of age.
* Histological diagnosis of squamous cell carcinoma of the skin not amenable to surgical treatment and to radiation with curative purposes or with clinical contraindication to surgery and radiation.
* Have metastatic disease
* Have measurable disease based on RECIST 1.1.
* Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion.
* Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
* Demonstrate adequate hematological, renal and hepatic organ function as defined in the study protocol.
* Women of childbearing potential should have a negative pregnancy within 72 hours prior to receiving the first dose of study medication.
* Women of childbearing potential must be willing to use an adequate method of contraception as outlined in the study protocol4
* Men of childbearing potential must be willing to use an adequate method of contraception as outlined in the study protocol

Exclusion Criteria:

* Current or past participation 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 of the first dose of treatment.
* Previous treatment with anti-EGFR agent
* Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (prednisone equivalent dose \> 10 mg per day) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
* Has a known history of active TB (Bacillus Tuberculosis)
* Hypersensitivity to the trials drugs or their excipients.
* Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
* Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (≤ Grade 1 or at baseline) from adverse events.
* Has a known additional malignancy that is progressing or requires active treatment.
* Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
* Has active autoimmune disease that has required systemic treatment in the past 2 years.
* Has known history of, or any evidence of active, non-infectious pneumonitis.
* Has an active infection requiring systemic therapy.
* Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with participation, or is not in the best interest of the subject.
* 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.
* Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
* 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., HCV RNA \[qualitative\] is detected).
* Has previously received an organ transplant
* Has previously received bone marrow transplantation
* Has received a live vaccine within 30 days of planned start of study therapy.