- This an open-label, two cohort, phase I/II research study to evaluate the safety and
effectiveness of Cemiplimab as a treatment for advanced cutaneous squamous cell
carcinoma in participants who have received allogeneic hematopoietic stem cell or kidney
- The research study procedures include screening for eligibility, study treatment,
participant evaluations and safety follow-up visits. It is expected that about 12 people
will take part in this research study.
- Participants will be divided into two groups (cohorts) of allogeneic hematopoietic
stem cell recipients or kidney transplants recipients.
- Allogeneic hematopoietic stem cell recipients will only receive the study treatment
drug of Cemiplimab.
- Kidney transplant recipients will receive the study treatment drug of Cemiplimab
along with the immunosuppressant drugs of Everolimus or Sirolimus and Prednisone to
prevent kidney rejection.
The U.S. Food and Drug Administration (FDA) has approved Cemiplimab as a treatment option for
patients with advanced cutaneous squamous cell cancer, but the FDA has not approved the use
of Cemiplimab in participants who have received allogeneic hematopoietic stem cell
transplants or kidney transplants in the past.
-- Cemiplimab is a type of drug called a monoclonal antibody. Antibodies are proteins
naturally found in your blood that fight infections. A monoclonal antibody is a special kind
of antibody that is manufactured as a medication to target specific proteins in the body that
may be involved this type of cancer.
Cemiplimab is a human monoclonal anti-PD-1 antibody that works by blocking the programmed
death-1 (PD-1), a cell receptor on immune cells that is involved in preventing immune cells
from destroying other cells. Blocking the receptor is expected to help immune cells attack
- 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
- 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 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 , Appendix A) ≥ 30
mL/min, baseline proteinuria lower than 0.5 g/day (spot urine protein-creatinine
ratio), and off antiproliferative immunosuppressive medications. Willing to provide
blood and tissue from diagnostic biopsies.
- Age 18 years or older.
- 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 < 3 mg/dL)
- AST(SGOT)/ALT(SGPT) ≤ 2.5 × institutional upper limit of normal
- creatinine ≤ 1.5 × institutional upper limit of normal OR
- estimated GFR ≥ 30 mL/min/1.73 m2 for participants with creatinine levels above
institutional normal (CKD-EPI equation).
- urine protein/creatinine ratio < 0.5 (equal to less than 500 mg of proteinuria
- Ability to understand and the willingness to sign a written informed consent document.
- A prior history of acute GVHD that has resolved, or sequelae of chronic GVHD following
allo-HSCT is permitted. Active acute GVHD patients are excluded.
- Women of childbearing potential (WOCBP) must agree to use at least 1 highly effective
form of contraception (refer to Appendix C for examples). WOCBP should plan to use an
adequate method to avoid pregnancy for up to 7 months (30 days plus the time required
for cemiplimab to undergo five half-lives) after the last dose of investigational
"Women of childbearing potential (WOCBP)" is defined as any female who has experienced
menarche, who has not undergone surgical sterilization (hysterectomy or bilateral
oophorectomy), who is not postmenopausal, who is sexually active with a male partner.
Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the
absence of other biological or physiological causes. In addition, women under the age of 55
must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL.
- Women of childbearing potential, as defined above, must have a negative serum or urine
pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24
hours prior to the start of cemiplimab.
- Men who are sexually active with WOCBP must agree to use any contraceptive method with
a failure rate of less than 1% per year. Men who are sexually active with WOCBP will
be instructed to adhere to contraception for a period of 7 months after the last dose
of investigational product. Women who are not of childbearing potential as defined
above, and azoospermic men) do not require contraception. See Appendix C for further
guidance on contraception
- Participants who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or those who have unresolved
toxicities from prior anti-cancer therapy more than 4 weeks earlier, defined as not
resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse
Events (CTCAE, version 5.0), grade 0 or 1.
- Participants who are receiving any other investigational agents.
- For Cohort 1 allo-HSCT patients enrolling to the study, corticosteroid doses > 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 also provide this information. As part of the
enrollment/informed consent procedures, the patient will be counseled on the risk of
interactions with other agents, and what to do if new medications need to be
prescribed or if the patient is considering a new over-the-counter medicine or herbal
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac
- Known non-infectious pneumonitis or any history of interstitial lung disease.