Cemiplimab-rwlc for Unresectable Locally Recurrent and/or Metastatic CSCC

Study Overview
=================
Brief 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).

Official Title
-----------------
A Single Arm Phase II Study of Cemiplimab-rwlc in Immunocompromised Patients With Unresectable Locally Recurrent and/or Metastatic Cutaneous Squamous Cell Carcinoma (CSCC)

Conditions
-----------------
Cutaneous Squamous Cell Carcinoma, Cutaneous Squamous Cell Carcinoma of the Head and Neck

Intervention / Treatment
-----------------
* Drug: Cemiplimab-Rwlc


Participation Criteria
=================
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cemiplimab-rwlc treatment<br>Immunocompromised patients will be given Cemiplimab-rwlc every 3 weeks | Drug: Cemiplimab-Rwlc<br>* Cemiplimab-rwlc will be administered as a flat dose of 350 mg IV over approximately 30 minutes every 21 days (+/- 3 days)<br>* Other names: Libtayo;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | Overall Response Rate (ORR) as indicated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 analysis of radiologic scans. In some patients, response assessments include photos and radiologic scans and will be evaluated by composite efficacy criteria. Clinical lesions will only be considered measurable when they are superficial (eg, skin nodules and palpable lymph nodes) and ≥10 mm (≥1 cm) diameter as assessed using calipers (e.g., skin nodules). Patients who are deemed as not evaluable according to RECIST 1.1 or inevaluable by the composite efficacy criteria will be considered as not reaching ORR. | Up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | Progression Free Survival (PFS), defined as time from on study date to disease progression | Up to 12 months | 
| Overall Survival | Overall Survival (OS), defined as time from on study date to death from any cause | Up to 12 months |