Cemiplimab with Radiation Therapy for the Treatment of Locally Advanced, Unresectable Cutaneous Squamous Cell Carcinoma (RAMPART)

Inclusion Criteria

• Biopsy proven cutaneous squamous cell carcinoma which is locally advanced * Mixed histology tumors that are predominantly squamous cell carcinoma are eligible * Locally advanced primary tumor is T3-T4 and/or N+ by American Joint Committee on Cancer (AJCC) and/or Union for International Cancer Control (UICC) 8th edition clinical criteria ** T3-T4 primary tumor characteristics noted below: *** Non-eyelid tumor > 4 cm in maximum dimension or with bone erosion or invasion, perineural invasion of nerve 0.1 mm or larger, or invasion beyond subcutaneous fat or > 6 mm from granular layer of adjacent normal epidermis *** Eyelid tumor > 2 cm or invading adjacent ocular, orbital or facial structures
• >= 18 years old
• Unresectable or medically inoperable according to local multidisciplinary consensus for reasons such as: * Tumor or regional lymph node metastases that has recurred despite >= 2 prior surgical procedures, with another curative resection unlikely * Tumor or nodal disease with significant local invasion that precludes complete resection * Tumor or nodal disease in anatomically challenging area where surgery may result in significant disfigurement or dysfunction (amputation of nose, ear, eye, digit, limb, etc) * Medical contraindication to surgery * Patient refusal of surgery due to anticipate morbidity
• Eastern Cooperative Oncology Group (ECOG) =< 2
• Total bilirubin =< 1.5 x upper limit of normal
• Aspirate aminotransferase (AST) =< 3 x upper limit of normal
• Alanine aminotransferase (ALT) =< 3 x upper limit of normal
• Alkaline phosphatase =< 2.5 x upper limit of normal
• Serum creatinine =< 1.5 x upper limit of normal or estimated creatinine clearance > 30 mL/min according to Cockcroft-Gault formula
• Hemoglobin > 9 g/dL
• Absolute neutrophil count >= 1.5 x 10^9/L
• Platelet count >= 75 x 10^9/L
• Able to provide informed consent
• Acceptable candidate for curative intent radiotherapy and cemiplimab immunotherapy, in opinion of radiation and medical oncologist, respectively
• Life expectancy > 18 months

Exclusion Criteria

• Primary tumor originating on the mucosal (non-hair bearing) lip or nose, anogenital (penis, scrotum, vulva, perianal) area
• Iatrogenic immunosuppression (> prednisone 10 mg/day or equivalent within 14 days of initiation of treatment)
• Women of child bearing potential unwilling or unable to use effective contraception while receiving treatment with cemiplimab and for 4 months thereafter
• Distant metastases
• Clinically significant autoimmune disease that requires iatrogenic immunosuppression * For example, severe rheumatoid arthritis requiring disease modifying antirheumatic drugs, such as methotrexate
• Current or previous hematopoietic malignancy (leukemia, lymphoma)
• Prior allogeneic transplant of solid organ or bone marrow
• Concurrent malignancies with > 10% risk of metastasis or death within 2 years
• Prior anti programmed cell death protein 1 (aPD1) immunotherapy or PI3K delta inhibitor use
• Prior radiotherapy for the cutaneous squamous cell carcinoma requiring treatment
• Other ongoing cancer therapy * Adjuvant endocrine therapy is permitted for patients with prostate or breast cancer
• Uncontrolled Human Immunodeficiency Virus (HIV) or infectious hepatitis (viral load detectable in patient with known infection)
• Pregnancy or breastfeeding
• Comorbid or diagnostic abnormalities within the last year that would interfere with interpretation of study results