Study of Ruxolitinib in Solid Organ Transplant Recipients With Advanced Cutaneous Squamous Cell Carcinoma

Inclusion Criteria: * Histopathologically confirmed diagnosis of metastatic advanced cutaneous squamous cell carcinoma. * History of solid-organ transplant requiring immunosuppression * Age ≥ 18 yrs * Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 * Karnofsky Performance Status Scale (KPS) ≥60%, Eastern Cooperative Oncology Group (ECOG) ≤2 * No prior Janus kinase (JAK) Inhibitor therapy * Adequate organ function * All clinically significant toxicities from prior systemic therapy must be ≤ Grade 1 (with the exception of alopecia, and peripheral neuropathy, which may be ≤ grade 2). * Subjects must agree to undergo tumor biopsies until biopsies have been obtained from 10 subjects (i.e., biopsies are required in at least the first 10 enrolled subjects, or until a goal of 10 study biopsies are obtained). Subjects in whom a biopsy is technically not feasible or in whom would result in unacceptable risk in the opinion of the investigator, may be exempted from the biopsy requirement with discussion with the principal investigator. * Negative pregnancy test for women of child bearing potential * Ability to take oral medications * Adequate marrow function: * Absolute neutrophil count (ANC) ≥1000 /mm3 * Platelet count ≥50,000/mm3 * Hemoglobin ≥8.0g/dL (not requiring transfusion in the past 2 weeks) Exclusion Criteria: * At least 21 days must have elapsed since the last dose of systemic chemotherapy or immunotherapy and the first dose of study drug. * At least 14 days must have elapsed since the last dose of radiation therapy and the first dose of study drug. * Patients who have previously been treated with a JAK inhibitor. * Patients who are receiving any other investigational agents concurrently. * Patients who have had recent major surgery within a minimum 4 weeks prior to starting study treatment, with the exception of surgical placement for vascular access. * Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to ruxolitinib. * Patients with symptomatic or growing brain metastases. Patients with brain metastases that have been treated and have remained stable for at least one month prior to initiation of study therapy are eligible. * Concurrent use of strong CYP3A4 or CYP3A4 substrate drugs with a narrow therapeutic range within 14 days or 5 drug half-lives, whichever is longer, before start of study drug. A list of strong CYP3A4 and 2C8 inhibitors and inducers can be found in Appendix A. * HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with ruxolitinib. In addition, these patients are at increased risk of lethal infections when treated with marrow- suppressive therapy. * Subjects with known active hepatitis B or C, or chronic hepatitis B or C requiring treatment with antiviral therapy. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Patients being actively treated for a second malignancy.