The purpose of this research is to evaluate whether the administration of atezolizumab before surgical resection of the tumor is feasible and to evaluate the treatment response, safety, and tolerability of atezolizumab.

Primary Objective:

Determine the feasibility of three doses of atezolizumab prior to surgery in patients with advanced cutaneous squamous cell carcinoma

Secondary Objectives:

• Assess response rates to neoadjuvant atezolizumab

  • Objective response rate following completion of neoadjuvant therapy based on RECIST 1.1 criteria
  • Pathological response rate (major and complete pathological response) in final surgical resection specimen

• Assess change in surgical margins or vital structures preserved following neoadjuvant treatment

• Assess safety and tolerability of neoadjuvant atezolizumab

Inclusion Criteria:

1. Signed Informed Consent Form

2. Age ≥ 18 years at time of signing Informed Consent Form

3. Histologically or cytologically confirmed squamous cell carcinoma

4. Measurable disease per RECIST v1 .1 • Note that protocol specified imaging is not necessary to fulfill this criterion. For example, a patient presenting with a visible 4cm primary lesion who has obviously RECIST evaluable disease may be considered eligible prior to baseline imaging stipulated in the protocol.

5. Availability of a representative tumor specimen that is suitable for determination of PD-L 1 immunohistochemical stain evaluation.

6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

7. Adequate hematologic and end-organ function appropriate for surgery as determined by routine preoperative evaluation. If liver function, renal function and hematologic laboratory test results are within limits acceptable for elective surgery.

   Laboratory results that will need to be obtained within 28 days prior to initiation of study treatment:

   • Aspartate aminotransferase (AST), Alanine aminotransferas (ALT), total bilirubin, and alkaline phosphatase (ALP) ≤ 2.5 x upper limit of normal (ULN.).

   • Thyroid-stimulating hormone (TSH) < 13

   • Patients with a history of a high TSH who are receiving levothyroxine replacement at the time of eligibility evaluation and have no clinical evidence of hypothyroidism are eligible.

8. For patients receiving therapeutic anticoagulation: stable anticoagulant regimen

9. Negative hepatitis B surface antigen (HBsAg) test at screening

10. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, as defined below: Women must remain abstinent or use contraceptive methods with a failure rate of < 1 % per year during the treatment period and for 5 months after the final dose of atezolizumab. A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state 3 (12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). The definition of childbearing potential may be adapted for alignment with local guidelines or requirements. Examples of contraceptive methods with a failure rate of< 1 % per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation

11. For men: Agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm, as defined below: With a female partner of childbearing potential or pregnant female partner, men must agree to remain abstinent or use a condom during the treatment period and for 5 months after the final dose of atezolizumab to avoid exposing the embryo.

Exclusion Criteria:

1. Patients not eligible for standard of care surgical resection

2. Distant metastatic disease

3. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) • Patients with indwelling catheters (e.g., PleurX) are allowed.

4. Uncontrolled or symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L, calcium > 12 mg/dl or corrected serum calcium > ULN)

5. Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjogren syndrome, Guillain-Barre syndrome, or multiple sclerosis, etc. with the following exceptions: • Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study.

   • Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.

   • Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
   • Rash must cover < 10% of body surface area
   • Disease is well controlled at baseline and requires only low-potency topical corticosteroids
   • No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months

6. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan History of radiation pneumonitis in the radiation field (fibrosis) is permitted.

7 .Active tuberculosis. Patents do NOT have to be screened for tuberculosis for this trial.

8. Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina

9. Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia

10. Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment

• Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.

  11. Prior allogeneic stem cell or solid organ transplantation

  12. Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications

  13. Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab

  14. Current treatment with anti-viral therapy for hepatitis B virus (HBV)

  15. Treatment with investigational therapy within 28 days prior to initiation of study treatment

  16. Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti- cytotoxic T-lymphocyteassociated protein 4 (CTLA-4 ), anti-PD-1, and anti-PD-L 1 therapeutic antibodies

  17. Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2)) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment

  18. Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor (TNF)-a agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions:](streamdown:incomplete-link)

9 weeks