Inclusion Criteria:
1. Male or female \> 18 years of age and able to comply with treatment, assessment and follow up
2. Documentation of a locally advanced cutaneous squamous cell carcinoma diagnosis as evidenced by histopathology with available archival tissue. Locally Advanced cutaneous Squamous Cell Carcinoma (LASCC) defined as borderline resectable for surgery due to multiple recurrences, prior radiotherapy, large extension, bone erosion and/or deep infiltration beyond the subcutaneous tissue into muscle/nerve or, where curative resection may lead to unacceptable complications, morbidity or deformity, and ineligible for curative radiotherapy
3. Measurable disease in accordance with iRECIST criteria OR clinically measurable disease \>1cm by caliper measurement. Patients with synchronous primary cutaneous squamous cell carcinoma (cSCC) tumours will be eligible.
4. Adequate bone marrow function with haemoglobin \>100g/L, absolute neutrophil count \> 1.5 x 109/L, platelets \> 100 x 109/L). Blood transfusion is allowable.
5. Adequate hepatic function with total bilirubin levels \<1.5 upper limit normal range and Alanine aminotransferase (ALT) and AST levels \<2.5 level normal range.
6. Adequate renal function with eGFR estimated with Cockcroft Gault formula \>50mL/min. Serum potassium levels 3.5 - 5.5 mmoL/L, Serum magnesium levels 0.7 - 1.05 mmol/L, Serum corrected calcium levels 2.15 - 2.55 mmol/L
7. Adequate performance status of Eastern Cooperative Oncology Group (ECOG) 0-1 as assessed by investigator
8. Life expectancy of \>6 months
9. Able to provide written informed consent obtained from patient and ability for patient to comply with the requirements of the trial.
Exclusion Criteria:
1. Distant metastatic disease (M1) including visceral or distant nodal metastases
2. Prior receipt of checkpoint inhibitor therapy or anti-EGFR therapy for LASCC or any other malignancy
3. Uncontrolled medical/psychiatric co-morbidity as per investigator that may jeopardize the ability of the patient to undergo trial procedures with reasonable safety
4. Uncontrolled autoimmune disease requiring active immune-suppression within 1 year of enrolment
5. Corticosteroid use of \>10mg daily of oral prednisone within 2 weeks of Cycle 1 Day 1 (C1D1)
6. Known history of interstitial lung disease, non-infectious pneumonitis or uncontrolled diseases including pulmonary fibrosis, acute lung diseases.
7. Uncontrolled infection with human immunodeficiency virus, hepatitis B, or hepatitis C infection; or has a diagnosis of immunodeficiency
8. Transplant recipient
9. Hepatitis C virus (HCV) and hepatitis B virus (HBV) testing will be performed at screening
10. Controlled HIV infection (undetectable viral load (HIV RNA PCR) and Cluster of differentiation 4 (CD4) counts above 350 either spontaneously or on a stable antiviral regimen) is permitted. Monitoring will be performed per local standards.
11. Controlled hepatitis B antibody positive infection (HBsAg+) is permitted providing a serum hepatitis B virus DNA PCR that is below the limit of detection and patient is receiving anti-viral therapy for hepatitis B. Periodic monitoring of HBV DNA is required. Anti-viral therapy for at least 6 months post the last dose of investigational study drug is required.
12. Controlled hepatitis C virus antibody positive (HCV Ab+) is permitted (undetectable HCV RNA by PCR either spontaneously or in response to a successful prior course of anti-HCV therapy).
13. History of another malignancy within 5 years prior to trial registration. A past history of adequately treated carcinoma-in-situ, basal cell carcinoma of skin, or superficial transitional cell carcinoma of the bladder is permitted. Patients with a history of other malignancies are eligible if they have been continuously disease free for at least 3 years after definitive primary treatment and low expected risk of recurrence.
14. Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with trial protocol and follow-up schedule, including alcohol and drug abuse.
15. Pregnancy, lactation or inadequate contraception. Women must be post-menopausal, infertile or willing to use reliable means of contraception. Women of childbearing potential must have a negative pregnancy test done within 7 days prior to registration. Men must have been surgically sterilized or willing to use double barrier contraception.
16. Sexually active men and women of childbearing potential who are unwilling to practice highly effective contraception prior to the start of the first treatment, during the study, and for at least 6 months after the last dose of investigational drug.
