Study of TVEC in Patients With Cutaneous Squamous Cell Cancer

Inclusion Criteria

• Able to give informed consent in English or Spanish
• Age > 18
• Have at least one >0.5 cm to 0.5 cm on trunk or extremities (excluding face, neck feet, nail units, and ankles)
• Clinically consistent with primary tumors.
• Lesion considered unresectable (as defined in Section 1.2)
• Recurrent lesions will be considered eligible if additional inclusion criteria are met.
• No immunosuppression
• Not a site of previous radiation therapy or chronic significant inflammation
• Fast growing lesions (doubling in size over a 4 week period of time) will be included if they are clinically suggestive of cSCC of the keratoacanthoma type.
• Well or moderately differentiated tumor as confirmed by skin biopsy
• Depth less than 2 mm (for non KA type cSCC )
• No perineural or vascular involvement in preliminary biopsy.
• Partial biopsy of squamous cell skin cancer identified as a target lesion(s) to determine the histological differentiation of the tumor or other adverse histological features
• In patients with multiple lesions, up to 3 lesions in a similar anatomical site, (trunk, limbs etc) that is at least 10 cm apart can be selected.
• Maximum of 5 lesions per patient can be selected for treatment
• Adequate organ function determined within 28 days prior to enrollment, defined as follows:
• Hematology:
• Absolute neutrophil count ≥ 1500/mm3 (1.5x109/L)
• Platelet count ≥ 75,000/mm3 (7.5x109/L)
• Hemoglobin ≥ 8 g/dL (without need for hematopoietic growth factor or transfusion support)
• Renal
• Serum creatinine ≤ 1.5 x upper limit of normal (ULN), OR 24-hour creatinine clearance ≥ 60 mL/min for subject with creatinine levels > 1.5 x ULN. (Note: Creatinine clearance need not be determined if the baseline serum creatinine is within normal limits. Creatinine clearance should be determined per institutional standard)
• Hepatic
• Serum bilirubin ≤ 1.5 x ULN
• Aspartate aminotransferase (AST) ≤ 2.5 x ULN 23 | Page Version 6-26-2018
• Alanine aminotransferase (ALT) ≤ 2.5 x ULN
• Coagulation
• International normalization ratio (INR) or prothrombin time (PT) ≤ 1.5 x ULN, unless the subject is receiving anticoagulant therapy, in which case PT and partial thromboplastin time (PTT)/ activated PTT (aPTT) must be within therapeutic range of intended use of anticoagulants.
• PTT or aPTT ≤ 1.5 x ULN unless the subject is receiving anticoagulant therapy as long as PT and PTT/aPTT is within therapeutic range of intended use of anticoagulants.
• Female subject of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to enrollment. If urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

Exclusion Criteria

• Any patient with diagnosis of invasive cancer in the last 3 years with the exception of stage I and II melanoma, cutaneous BCC and SCCs will be excluded.
• Subjects on acitretin, capecitabine, topical chemotherapies or treatments.
• History or evidence of symptomatic autoimmune disease (eg, pneumonitis, glomerulonephritis, vasculitis, or other), or history of active autoimmune disease that has required systemic treatment (ie, use of corticosteroids, immunosuppressive drugs or biological agents used for treatment of autoimmune diseases) in past 2 months prior to enrollment. Replacement therapy (eg, thyroxine for hypothyroidism, insulin for diabetes or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment for autoimmune disease.
• Evidence of clinically significant immunosuppression such as the following:
• Primary immunodeficiency state such as Severe Combined Immuno deficiency Disease
• Acquired immunodeficiency syndrome
• Concurrent opportunistic infection
• Receiving systemic immunosuppressive therapy (> 2 weeks) including oral steroid doses > 10 mg/day of prednisone or equivalent within 2 months prior to enrollment.
• Active herpetic sk