Cemiplimab in AlloSCT/SOT Recipients With CSCC

Inclusion Criteria

• Patients must have histologically confirmed, advanced or metastatic cutaneous squamous cell carcinoma (cSCC) with 1 or more measurable lesions (greater than or equal to 1 cm).
• A history of either (Cohort 1) allogeneic hematopoietic stem cell transplant (alloHSCT) and ≥ 2 years or 730 days from day 0 of their HSCT with adequate bone marrow function (see Section 3.1.6) and off of all systemic immunosuppression (topical agents permitted) for at least 3 months prior to enrollment; sequelae of chronic graft versus host disease (GVHD) is permitted (i.e. chronic dry eyes, sclerodermatous skin changes, etc.) if the patient is not on systemic immunosuppression, or (Cohort 2) a renal transplant with a functioning allograft (at least 6 months from allograft transplant) as determined by estimated glomerular filtration (GFR) rate (CKD-EPI equation [40], Appendix A) ≥30 mL/min, baseline proteinuria lower than 0.5 g/day (spot urine protein-creatinine ratio), and off antiproliferative immunosuppressive medications.
• Age 18 years or older.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%, see Appendix B).
• Participants must have adequate organ and marrow function as defined below:
• leukocytes ≥ 2,200/mcL
• absolute neutrophil count ≥ 1,000/mcL
• platelets ≥ 90,000/mcL
• total bilirubin within normal institutional limits (except in cases where Gilbert syndrome is known or suspected, where total bilirubin should be 10 mg of prednisone daily or equivalent within 4 weeks of the first dose of PD-1 inhibitor are prohibited. For Cohort 2 renal transplant patients enrolling to the study, corticosteroid use is permitted if used as part of their immunosuppressive regimen for graft protection prior to enrollment.
• Existing significant autoimmune conditions. Patients with a history of Hashimoto thyroiditis who are stable on replacement hormone therapy are not excluded.
• Known human immunodeficiency virus carrier or a diagnosis of immunodeficiency. Any positive test result for hepatitis B virus or hepatitis C virus indicating presence of virus, e.g., Hepatitis B surface antigen (HBsAg, Australia antigen) positive, or Hepatitis C antibody (anti-HCV) positive (except if HCV-RNA negative).
• Kidney transplant recipients with active acute rejection.
• Allergy to cemiplimab or any of its components.
• Any prior exposure to the phosphoinositide 3-kinase inhibitor idelalisib.
• Subject who has been treated with immunotherapy. This includes prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways (including chimeric antigen receptor [CAR] T cell therapies). Prior topical or intralesional immunotherapies (e.g. imiquimod, talimogene laherparepvec) are allowed.
• Subject with known and untreated brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. However, baseline brain imaging is not required prior to enrollment in the study if patients are asymptomatic. Patients at least 4 weeks out from metastatic central nervous system (CNS) treatment are permitted to enroll, if they are asymptomatic, radiographically stable per the investigator, and on stable doses of anti-epileptic drugs (AEDs) and oral corticosteroids (for Cohort 1 only, the patient must be on 10 mg of prednisone daily equivalent dosing or less, see 3.2.2) at the time of enrollment.
• Participants receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list such as [http://medicine.iupui.edu/clinpharm/ddis/table.aspx]. Medical reference texts such as the Physicians' Desk Reference may al