Evaluation of Efficacy and Safety of Cemiplimab as First Line Treatment for Advanced Basal Cell Carcinoma (BCC) Patients

Inclusion Criteria:

1. Signed informed consent form available

2. Patient* 18 years or older at time of signing informed consent form

3. Centrally confirmed histological diagnosis of BCC NOTE: Tumor tissue to be sent to Central Pathology during screening procedure:

• Formalin-fixed, parrafin-embedded (FFPE) tumor specimen in a paraffin block (preferred) OR

• approximately 10 sections (5µm thickness) on uncoated slides and 10 sections (5µm thickness) on Superfrost Ultra slides containing unstained, freshly cut,serial sections to be submitted along with associated pathology report (pleaserefer to section 11.1.1 for details)

4. Locally advanced stage without distant metastases, not amenable for surgery orradiotherapy or surgery/radiotherapy contraindicated or refused by patient (asevidenced in source data)

5. Expected survival of at least 6 months

6. ECOG performance status 0 or 1

7. Adequate laboratory parameters particularly for the blood count, renal and liverfunction parameters.

8. Absolute number of neutrophils ≥ 1.5 x 109/L

9. Platelets ≥ 75 x 109/L

10. Hemoglobin ≥ 9 g/dL

11. Total bilirubin ≤ 1.5 times the upper limit of normal (ULN), (patients withGilbert´s Disease and total bilirubin up to 3x ULN may be eligible afterapproval from trial's medical expert)

12. AST (SGOT) and ALT (SGPT) ≤ 3x ULN

13. AP ≤ 2.5x ULN

14. Serum creatinine ≤ 2x ULN or creatinine clearance ≥ 40 mL/min

15. Absence of other severe comorbidities

16. Resolution of any acute, clinically significant treatment-related adverse eventsfrom prior therapy/procedure to Grade ≤ 1 prior to study entry, with the exceptionof alopecia.

17. Negative serum pregnancy test done less than or equal to 7 days prior to enrollment,for females of childbearing potential only.

18. Sexually active women of childbearing potential (WOCBP) and men with WOCBP partnersmust be prepared to use suitable contraceptive method with a failure rate of < 1%per year during the treatment period and for at least 6 months after the last doseof Cemiplimab

• There are no data that indicate special gender distribution. Therefore,patients will be enrolled in the study gender-independently

Exclusion Criteria:

1. Pretreatment with systemic immunotherapy (such as PD-1/PD-L1 or CTL4) or targetedtherapy (such as hedgehog inhibitor) NOTE: Prior treatment with imiquimod or othertopical or intralesional immune modulators will not be exclusionary

2. Any other non-radiation anti-cancer therapy (e.g. imiquimod, photodynamic therapy;neither investigational nor standard of care) within 30 days (from date of lastadministration) of initial Cemiplimab administration or if planned during the studyduration

3. Ongoing or recent (within 5 years) evidence of significant autoimmune disease thatrequired systemic immunosuppressive therapy, excluding: vitiligo, childhood asthmathat has resolved, type 1 diabetes, residual hypothyroidism requiring only hormonereplacement, or psoriasis that does not require systemic treatment

4. Other neoplasia, in particular hematologic diseases that might impair immuneresponse, such as chronic lymphocytic leukemia, myelodysplastic ormyeloproliferative disease and patients with Gorlin-Goltz syndrom

5. Immunosuppressive corticosteroid doses (> 10 mg prednisone daily or equivalent)within 4 weeks prior to the first dose of Cemiplimab NOTE: Patients who requirebrief courses of steroids (e.g., as prophylaxis for imaging studies due tohypersensitivity to contrast agents) are eligible for participation. Furthermore,patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroidsfor chronic obstructive pulmonary disease (COPD) or asthma, or low-dosecorticosteroids for orthostatic hypotension or replacement in case of adrenal orhypophysis insufficiency are eligible for participation.

6. Known allergic/hypersensitive reaction to the study drug and any of its excipientsor history of documented allergic/hypersensitive reactions to antibody treatments

7. Active infection requiring systemic therapy, including uncontrolled HIV, HBV and HCVinfection or diagnosis of immunodeficiency. NOTE: Patients are eligible if:

• Patients have controlled HIV infection with CD4 counts is > 350 cells/µL andviral load is undectable [HIV RNA PCR]

• Patients positive for HBV surface antigen have controlled HBV infectionreceiving anti-viral therapy and with undectable serum viral load [HBV DNAPCR]. Patients must remain on anti-viral therapy for at least 6 months afterlast dose of Cemiplimab

• Patients positive for HCV antibody have controlled HCV infection withundectable viral load [HCV RNA PCR]

8. History of pneumonitis within the last 3 years

9. Patients with history of solid organ transplant (patients with prior cornealtransplants may be allowed to enroll after discussion with and approval from theLead Investigator)

10. Comorbid systemic illnesses or other severe concurrent disease which, in thejudgment of the investigator, would make the patient inappropriate for entry intothis study or interfere significantly with the proper assessment of safety andtoxicity of the prescribed regimens

11. Receipt of live vaccines (including attenuated) within 30 days of firstadministration of Cemiplimab

12. Pregnancy or lactation period.

13. Medical or psychological conditions that would not permit the patient to completethe study or sign informed consent.

14. Substance abuse, medical, psychological or social conditions that may interfere withthe patient's participation in the study or evaluation of the study results

15. Legal incapacity or limited legal capacity.

16. On-treatment participation in another clinical trial in the period 30 days prior tostart of the study treatment and during the study