Cemiplimab-rwlc for Unresectable Locally Recurrent and/or Metastatic CSCC
Condition: Cutaneous Squamous Cell Carcinoma; Cutaneous Squamous Cell Carcinoma of the Head and Neck
MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
Intervention: Cemiplimab-Rwlc
Intervention description: Cemiplimab-rwlc will be administered as a flat dose of 350 mg IV over approximately 30 minutes every 21 days (+/- 3 days)
Intervention MeSH terms: Cemiplimab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this research study is to determine how people with weakened immune systems
      and unresectable (cannot be removed by surgery) locally recurrent and/or metastatic cutaneous
      squamous cell carcinoma (CSCC) respond to study treatment with Cemiplimab. Cemiplimab is
      approved for sale in United States by the U.S. Food and Drug Administration (FDA).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed diagnosis of invasive Cutaneous Squamous Cell Carcinoma
             (CSCC)

          -  Immunocompromised patients with invasive CSCC. Immunocompromised patients are defined
             as: (a) History of HIV with CD4 counts >/= 200 and no AIDS-defining illness (b)
             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 RECIST 1.1. Externally
             visible cutaneous Squamous Cell Cancer (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

          -  Laboratory values as defined per protocol

          -  Ability to sign informed consent

          -  Ability and willingness to comply with scheduled visits, treatment plans, laboratory
             tests, and other study-related procedures.

          -  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

          -  Immunocompromised patients due to solid organ transplant, allogenic bone marrow
             transplant, and/or autoimmune disease.

          -  Untreated brain metastasis(es) that may be considered active.

          -  Immunosuppresive corticosteroid doses (>10 mg prednisone daily or equivalent for >5
             consecutive days) within 4 weeks prior to the first dose of Cemiplimab-rwlc.

          -  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 trail. 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: (a) Patients receiving bisphosphonates or denosumab are not excluded. (b) Patients
        receiving maintenance or supportive therapies for their hematological malignancies are not
        excluded. (c) 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
             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 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.