Cemiplimab for the Treatment of Immunocompromised Patients with Unresectable Locally Recurrent and/or Metastatic Cutaneous Squamous Cell Carcinoma

Inclusion Criteria

• Histologically confirmed diagnosis of invasive CSCC. * Notes: Patients with mixed histologies (e.g., sarcomatoid, adenosquamous) generally will not be eligible. Patients with mixed histology in which the predominant histology is invasive CSCC (with only a minimal component of mixed histology) may be eligible, after communication with and approval from the each site principal investigator
• Immunocompromised patients with invasive CSCC. Immunocompromised patients are defined as: * History of human immunodeficiency virus (HIV) with CD4 counts >= 200 and no acquired immunodeficiency syndrome (AIDS)-defining illnesses * History of treated or active hematologic malignancies including lymphoma, Hodgkin’s disease, chronic lymphocytic leukemia, chronic myeloid leukemia, multiple myeloma, and myeloproliferative neoplasm
• At least 1 lesion that is measurable by study criteria by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Externally visible cutaneous squamous cell carcinoma (SCC) target lesion(s) greater than > 10 mm, bi-dimensional measurements of the external lesion(s) with a color photograph may be used as target lesions
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Total bilirubin =< 3.0 X upper limit of normal (ULN)
• Transaminases =< 5.0 X ULN
• Alkaline phosphatase (ALP) =< 5.0 X ULN
• Estimated creatinine clearance (CrCl) > 30 mL/min
• Hemoglobin >= 8.0 g/dL
• Absolute neutrophil count (ANC) >= 1.0 x 10^9/L
• Platelet count >= 50 x 10^9/L
• Ability to provide signed informed consent
• Ability and willingness to comply with scheduled visits, treatment plans, laboratory tests, and other study-related procedure
• Anticipated life expectancy > 12 weeks
• CSCC not amenable to surgery or radiation therapy such as unresectable tumors determined by surgeons, surgical morbidity unacceptable by the patients, inability to deliver radiation safely determined by radiation oncologists, or radiation related toxicities unacceptable by the patients * Note: In lieu of individual consults performed during screening, it will suffice to document the contraindication of surgery and radiation therapy via a clinic note from the investigator indicating that an individualized benefit:risk assessment was performed by a multidisciplinary team (consisting of, at minimum, a radiation oncologist AND EITHER a medical oncologist with expertise in cutaneous malignancies OR a dermato-oncologist, OR a head and neck surgeon) within 60 days prior to enrollment in the proposed study, and the radiation therapy was deemed to be contraindicated. This is not required for patients with distant metastatic disease

Exclusion Criteria

• Prior known allergy to cemiplimab-rwlc
• Prior exposure to PD-1 or PD-L1 inhibitors
• Prior exposure to idelalisib * Note: Patients who have previously been treated with idelalisib will be excluded from treatment with cemiplimab as a result of the safety findings for 3 patients with indolent lymphoma previously treated with idelalisib, a phosphatidylinositol 3-kinase (PI 3-K) inhibitor, in study R1979-ONC-1504. Following a single dose of cemiplimab monotherapy in each case, 2 patients experienced severe stomatitis and/or skin reactions. The third patient experienced myositis and myasthenia gravis after 2 doses of cemiplimab
• Immunocompromised patients due to the solid organ transplant, allogeneic bone marrow transplant, and/or autoimmune disease
• Untreated brain metastasis(es) that may be considered active * Note: Patients with brain involvement of CSCC due to direct extension of invading tumor, rather than metastasis, may be allowed to enroll if they do not require greater than 10 mg prednisone daily. Patients with previously treated brain metastases may participate provided that the lesion(s) is (are) stable (without evidence of progression for at least 4 weeks on imaging obtained in the screening period), and there is no evidence of new or enlarging brain metastases, and the patient does not require any immunosuppressive doses of systemic corticosteroids for management of brain metastasis(es) within 4 weeks of first dose of cemiplimab-rwlc
• Immunosuppressive corticosteroid doses (> 10 mg prednisone daily or equivalent for > 5 consecutive days) within 4 weeks prior to the first dose of cemiplimab-rwlc. * Note: Patients who require brief course of steroids (e.g., as prophylaxis for imaging studies due to hypersensitivity to contrast agents) are not excluded
• Known active infection requiring therapy, including acute infection with hepatitis B virus (HBV) or hepatitis C virus (HCV). However, it is not required to test only to determine the eligibility for the trial. As an exception, known HIV infection is allowed
• History of pneumonitis within the last 5 years
• Grade >= 3 hypercalcemia at time of enrollment
• Patients on any systemic anticancer treatment (chemotherapy, targeted systemic therapy, photodynamic therapy), investigational or standard of care for CSCC within 28 days of the initial administration of cemiplimab-rwlc are excluded
• Patients on any systemic anticancer treatment (chemotherapy, targeted systemic therapy, photodynamic therapy), investigational or standard of care for non-hematologic malignancy within 28 days of the initial administration of cemiplimab-rwlc or planned to occur during the study period are excluded. Note: * Patients receiving bisphosphonates or denosumab are not excluded * Patients receiving maintenance or supportive therapies for their hematological malignancies are not excluded * If the patients have been disease free for >= 2 years, patients receiving adjuvant hormonal therapies for breast cancer, prostate cancer, or thyroid cancer are not excluded
• Patients who cannot discontinue the concurrent use of other chemopreventive agents such as 5-FU, capecitabine, Efudex, imiquimod, acitretin are not allowed
• Radiation therapy within 7 days of initial administration of cemiplimab-rwlc or planned to occur during the study period
• Breast feeding
• Positive serum pregnancy test (a false positive pregnancy test, if demonstrated by serial measurements and negative ultrasound, will not be exclusionary)
• Concurrent non-hematologic malignancy other than cutaneous SCC within 3 years of date of first planned dose of cemiplimab-rwlc, except for tumors with negligible risk of metastasis or death, such as adequately treated basal cell carcinoma of the skin, carcinoma in situ of the cervix, or ductal carcinoma in situ of the breast, or low-risk early stage prostate adenocarcinoma (T1-T2a N0 M0 and Gleason score =< 6 and prostate specific antigen [PSA] =< 10 ng/mL) for which the management plan is active surveillance, or prostate adenocarcinoma with biochemical-only recurrence with documented PSA doubling time of > 12 months for which the management plan is active surveillance
• Any acute or chronic psychiatric problems that, in the opinion of the investigator, make the patient ineligible for participation
• Continued sexual activity in men or women of childbearing potential who are unwilling to practice highly effective contraception during the study and until 6 months after the last dose of study drug. * Note: Highly effective contraceptive measures include stable use of oral contraceptives such as combined estrogen and progestogen only hormonal contraception or other prescription pharmaceutical contraceptives for 2 or more menstrual cycles prior to screening; intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal ligation; vasectomy, and sexual abstinence