Clinical trial NCT04242173
Conditions: Cutaneous Squamous Cell Carcinoma Cutaneous Squamous Cell Carcinoma of the Head and Neck
Sponsor: H. Lee Moffitt Cancer Center and Research Institute
Start date: 2020-06-25; Completion date: 2022-05-26
Enrollment: 3 participants; Allocation: NA; Intervention model: SINGLE_GROUP

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).

Detailed description:

Arms: arm 1: Immunocompromised patients will be given Cemiplimab-rwlc every 3 weeks
Interventions: intervention 1: Cemiplimab-Rwlc
Intervention descriptions: intervention 1: Cemiplimab-rwlc will be administered as a flat dose of 350 mg IV over approximately 30 minutes every 21 days (+/- 3 days)

Protocol documents:
Prot_SAP_000.pdf: 
A Single Arm Phase II Study of  
Cemiplimab-rwlc in Immunocompromised 
Patients with Unresectable Locally Recurrent 
and/or Metastatic Cutaneous Squamous Cell 
Carcinoma (CSCC) 
 
NCT04242173 
 
Protocol Version 4 Dated 10/29/2020 


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A Single Arm Phase II Study of Cemiplimab-rwlc in 
Immunocompromised Patients with Unresectable Locally Recurrent 
and/or Metastatic Cutaneous Squamous Cell Carcinoma (CSCC) 
 
Protocol Identifying Number: MCC 20114  
Principal Investigator: Christine H. Chung, M.D. 
 
Participating Site Principal Investigators:  
Anne Chang: Stanford University 
 Stuart Wong: Medical College of Wisconsin 
Nabil Saba: Emory University 
Julie Bauman: University of Arizona 
Lara Dunn: Memorial Sloan Kettering 
 
Biostatistician: Michael Schell, Ph.D. 
IND/IDE Sponsor: Exempt 
Funded by: Regeneron Pharmaceuticals, Inc. 
Version Number:  v4.0 
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TABLE OF CONTENTS 
Table of Contents 
LIST OF ABBREVIATIONS .......................................................................................................vi 
STATEMENT OF COMPLIANCE .............................................................................................vii 
STUDY SUMMARY ................................................................................................................. viii 
SCHEMA OF STUDY DESIGN ................................................................................................ix 
1 
KEY ROLES ..............................................................................................................10 
2 
INTRODUCTION: BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE
 
11 
2.1 
BACKGROUND INFORMATION .............................................................................11 
2.2 
RATIONALE ...............................................................................................................12 
2.3 
POTENTIAL RISKS AND BENEFITS ......................................................................12 
2.3.1 
KNOWN POTENTIAL RISKS ...............................................................................12 
ALLERGIC REACTION RISK: .................................................................................................14 
2.3.2 KNOWN POTENTIAL BENEFITS .......................................................................14 
3 
OBJECTIVES ............................................................................................................14 
4 
STUDY DESIGN AND ENDPOINTS ......................................................................15 
4.1 
DESCRIPTION OF THE STUDY DESIGN ..............................................................15 
4.2.1 PRIMARY ENDPOINT .........................................................................................15 
4.2.2 SECONDARY ENDPOINTS ................................................................................15 
4.2.3 EXPLORATORY ENDPOINTS ............................................................................15 
5 
STUDY ENROLLMENT AND WITHDRAWAL ........................................................15 
5.1 
PARTICIPANT INCLUSION CRITERIA .....................................................................15 
5.2 
PARTICIPANT EXCLUSION CRITERIA ....................................................................16 
5.4 
PARTICIPANT WITHDRAWAL OR TERMINATION .................................................18 
5.4.1 
REASONS FOR WITHDRAWAL OR TERMINATION ....................................18 
5.4.2 HANDLING OF PARTICIPANT WITHDRAWALS OR TERMINATION .............19 
5.5 
PREMATURE TERMINATION OR SUSPENSION OF STUDY ...............................19 
6 
STUDY AGENT .........................................................................................................19 
6.1 
STUDY AGENT(S) AND CONTROL DESCRIPTION ..............................................19 
6.1.1 ACQUISITION ......................................................................................................20 
6.1.2 FORMULATION, APPEARANCE, PACKAGING, AND LABELING ..................20 
6.1.3 PRODUCT STORAGE AND STABILITY ...........................................................20 
6.1.4 PREPARATION ...................................................................................................20 
6.1.5 DOSING AND ADMINISTRATION .....................................................................20 
6.1.6 ROUTE OF ADMINISTRATION .........................................................................21 
6.1.7 
STARTING DOSE AND DOSE ESCALATION SCHEDULE .........................21 
6.1.8 DOSE ADJUSTMENTS/MODIFICATIONS/DELAYS ...........................................21 
6.1.9 DURATION OF THERAPY ..................................................................................22 


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6.1.10 TRACKING OF DOSE ..........................................................................................22 
6.1.11 DEVICE SPECIFIC CONSIDERATIONS ..............................................................22 
6.2 
STUDY AGENT ACCOUNTABILITY PROCEDURES ...........................................22 
7 
STUDY PROCEDURES AND SCHEDULE .............................................................22 
7.1 
STUDY PROCEDURES/EVALUATIONS ..................................................................22 
7.1.1 
STUDY-SPECIFIC PROCEDURES ..................................................................22 
7.1.2 STANDARD OF CARE STUDY PROCEDURES ..............................................22 
7.2 
LABORATORY PROCEDURES/EVALUATIONS .....................................................22 
7.2.1 CLINICAL LABORATORY EVALUATIONS .......................................................23 
7.2.2 
OTHER ASSAYS OR PROCEDURES ..............................................................23 
7.2.3 
SPECIMEN PREPARATION, HANDLING, AND STORAGE ................................24 
7.2.4 SPECIMEN SHIPMENT .......................................................................................26 
7.3 
STUDY SCHEDULE .................................................................................................26 
7.3.1 SCREENING ........................................................................................................26 
7.3.2 ENROLLMENT/BASELINE ..................................................................................27 
7.3.3 TREATMENT VISITS ...........................................................................................27 
7.3.4 
END OF TREATMENT VISIT .............................................................................28 
7.3.5 
FOLLOW-UP ......................................................................................................28 
7.3.6 
UNSCHEDULED VISIT .....................................................................................28 
7.3.7 
SCHEDULE OF EVENTS TABLE .....................................................................30 
7.4 
CONCOMITANT MEDICATIONS, TREATMENTS, AND PROCEDURES ...........32 
7.5 
JUSTIFICATION FOR SENSITIVE PROCEDURES .................................................32 
7.5.1 PRECAUTIONARY MEDICATIONS, TREATMENTS, AND PROCEDURES .32 
7.6 
PROHIBITED MEDICATIONS, TREATMENTS, AND PROCEDURES ..................32 
7.7 
PROPHYLACTIC MEDICATIONS, TREATMENTS, AND PROCEDURES ............32 
7.8 
RESCUE MEDICATIONS, TREATMENTS, AND PROCEDURES ........................32 
7.9 
PARTICIPANT ACCESS TO STUDY AGENT AT STUDY CLOSURE ................34 
8 
ASSESSMENT OF SAFETY ...................................................................................34 
8.1 
SPECIFICATION OF SAFETY PARAMETERS ........................................................34 
8.1.1 
DEFINITION OF ADVERSE EVENTS (AE) ....................................................34 
8.1.2 
DEFINITION OF SERIOUS ADVERSE EVENTS (SAE) ................................34 
8.1.3 DEFINITION OF UNANTICIPATED PROBLEMS .............................................35 
8.2 
CLASSIFICATION OF AN ADVERSE EVENT .......................................................35 
8.2.1 
SEVERITY OF EVENT........................................................................................35 
8.2.2 RELATIONSHIP TO STUDY AGENT ................................................................35 
8.2.3 EXPECTEDNESS ................................................................................................36 
8.3 
TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND 
FOLLOW-UP ............................................................................................................36 
8.4 
REPORTING PROCEDURES ...................................................................................36 
8.4.1 
ADVERSE EVENT REPORTING ......................................................................36 
8.4.2 SERIOUS ADVERSE EVENT REPORTING ......................................................37 


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8.4.3 UNANTICIPATED PROBLEM REPORTING .......................................................37 
8.4.4 
EVENTS OF SPECIAL INTEREST ...................................................................37 
8.4.5 REPORTING OF PREGNANCY........................................................................37 
8.5 
STUDY HALTING RULES .........................................................................................37 
8.6 
SAFETY OVERSIGHT ..............................................................................................37 
9 
CLINICAL MONITORING .........................................................................................38 
10 
STATISTICAL CONSIDERATIONS ..........................................................................38 
10.1 STATISTICAL AND ANALYTICAL PLANS ............................................................38 
10.2 STATISTICAL HYPOTHESES .................................................................................38 
10.3 ANALYSIS DATASETS .............................................................................................38 
10.4 DESCRIPTION OF STATISTICAL METHODS .......................................................39 
10.4.1 GENERAL APPROACH .....................................................................................39 
10.4.2 ANALYSIS OF THE PRIMARY EFFICACY ENDPOINT(S) ............................39 
10.4.3 ANALYSIS OF THE SECONDARY ENDPOINT(S) ..........................................39 
10.4.4 SAFETY ANALYSES .........................................................................................39 
10.5 SAMPLE SIZE ..........................................................................................................39 
11 
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS ...39 
12 
QUALITY ASSURANCE AND QUALITY CONTROL .............................................40 
13 
ETHICS/PROTECTION OF HUMAN SUBJECTS ...................................................40 
13.1 ETHICAL STANDARD ..............................................................................................40 
13.2 INSTITUTIONAL REVIEW BOARD .........................................................................40 
13.3 INFORMED CONSENT PROCESS .........................................................................40 
13.3.1 CONSENT/ASSENT AND OTHER INFORMATIONAL DOCUMENTS PROVIDED 
TO PARTICIPANTS .............................................................................................40 
13.3.2 CONSENT PROCEDURES AND DOCUMENTATION ......................................40 
13.4 PARTICIPANT AND DATA CONFIDENTIALITY ......................................................41 
13.4.1 RESEARCH USE OF STORED HUMAN SAMPLES, SPECIMENS, OR DATA 41 
13.5 FUTURE USE OF STORED SPECIMENS.............................................................41 
14 
DATA HANDLING AND RECORD KEEPING .........................................................42 
14.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES .......................42 
14.2 STUDY RECORDS RETENTION .............................................................................42 
14.3 PROTOCOL DEVIATIONS ........................................................................................42 
14.4 PUBLICATION AND DATA SHARING POLICY ....................................................43 
15 
STUDY ADMINISTRATION ......................................................................................44 
15.1 STUDY LEADERSHIP ..............................................................................................44 
16 
PARTICIPATING SITES .........................................................................................44 
16.1 REQUIRED DOCUMENTATION ............................................................................44 
16.2 SAE REPORTING ...................................................................................................45 
16.3 REGISTRATION PROCEDURES ..........................................................................45 
17 
CONFLICT OF INTEREST POLICY ........................................................................46 
18 
LITERATURE REFERENCES .................................................................................46 


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APPENDIX ...............................................................................................................................48 
APPENDIX 1: MANAGEMENT ALGORITHMS .....................................................................48 
APPENDIX 2: COMPOSITE RESPONSE CRITERIA FOR PATIENTS WITH LOCALLY 
ADVANCED CSCC ....................................................................................................54 
 


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LIST OF ABBREVIATIONS 
 
AE 
Adverse Event 
ANCOVA Analysis of Covariance 
CFR 
Code of Federal Regulations 
CIOMS 
Council for International Organizations of Medical Science 
CLIA 
Clinical Laboratory Improvement Amendments 
CMP 
Clinical Monitoring Plan 
CMS 
Centers for Medicare and Medicaid Services 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
DCC 
Data Coordinating Center 
DHHS 
Department of Health and Human Services 
DSMB 
Data Safety Monitoring Board 
eCRF 
Electronic Case Report Forms 
FDA 
Food and Drug Administration 
FDAAA 
Food and Drug Administration Amendments Act of 2007 
FFR 
Federal Financial Report 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practices 
GMP 
Good Manufacturing Practices 
GWAS 
Genome-Wide Association Studies 
HIPAA 
Health Insurance Portability and Accountability Act 
IB 
Investigator’s Brochure 
ICH 
International Conference on Harmonisation 
ICH E6 
International Conference on Harmonisation Guidance for Industry, Good Clinical 
Practice: Consolidated Guidance 
ICMJE 
International Committee of Medical Journal Editors 
IDE 
Investigational Device Exemption 
IND 
Investigational New Drug Application 
IRB 
Investigational Review Board 
ISO 
International Organization for Standardization 
LSMEAN
Least Squares Means 
MedDRA Medical Dictionary for Regulatory Activities 
MOP 
Manual of Procedures 
MSDS 
Material Safety Data Sheet 
NIH 
National Institutes of Health 
NIH IC 
NIH Institute & Center 
OHRP 
Office for Human Research Protections 
PI 
Principal Investigator 
QA 
Quality Assurance 
QC 
Quality Control 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SMC 
Safety Monitoring Committee 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
UP 
Unanticipated Problem 
US 
United States 


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STATEMENT OF COMPLIANCE 
 
 
 
The trial will be conducted in accordance with the ICH E6, the Code of Federal Regulations on 
the Protection of Human Subjects (45 CFR Part 46), and the <NIH IC> Terms of Award. The 
Principal Investigator will assure that no deviation from, or changes to the protocol will take 
place without prior agreement from the sponsor and documented approval from the Institutional 
Review Board, except where necessary to eliminate an immediate hazard(s) to the trial 
participants. All personnel involved in the conduct of this study have completed Human 
Subjects Protection Training. 
 
I agree to ensure that all staff members involved in the conduct of this study are informed of 
their obligation to meet the above commitments. 
 
 
Principal Investigator:    
 
Print/Type Name 
 
 
Signed:    
 Date: 
 


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STUDY SUMMARY 
 
 
 
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) 
                                       
Primary Objective: Determine the overall response rate of Cemiplimab-rwlc in 
immunocompromised patients with unresectable locally recurrent and/or metastatic CSCC. 
 
Secondary Objective:  
1. Evaluate progression-free survival 
2. Evaluate overall survival 
3. Evaluate acute and late toxicities 
 
Exploratory Objective: 
1. Identify potential biomarkers related to response to Cemiplimab-rwlc in immunocompromised 
patients with unresectable locally recurrent and/or metastatic CSCC.  
2. Evaluate overall response rate of underlying chronic lymphocytic leukemia (CLL) in the CLL 
subset. 
 
Primary Endpoint: Overall response rate of CSCC 
 
Secondary Endpoint: 
1. Progression-free survival 
2. Overall survival 
3. Acute and late immune-related and non-immune-related toxicities 
Exploratory Endpoint: 
1. Predictive biomarkers of Cemiplimab-rwlc response in CSCC  
2. Overall response rate of underlying CLL in the CLL subset  
 
Population: Immunocompromised patients with unresectable locally recurrent and/or metastatic 
CSCC. 
  
Sample size: 27 patients.  
 
Study groups: immunocompromised patients with unresectable locally recurrent and/or 
metastatic CSCC 
 
Phase: Phase II 
 
Number of Sites enrolling participants: 6 
 
 
Description of Study Agent: Cemiplimab-rwlc    
 
Study Duration: 
24 months 
 
Treatment Duration: 
12 months 
 
 


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SCHEMA OF STUDY DESIGN 
Immunocompromised patients with 
unresectable locally recurrent and/or 
metastatic cutaneous squamous cell 
carcinoma (CSCC) 
Cemiplimab-rwlc 350 mg IV Q 3 weeks 
All patients will have baseline CT or MRI scans. 
Histologically confirmed CSCC 
Treat until disease progression, 
intolerable toxicity, 
 
withdrawal of consent by the patient, 
or up to 17 cycles (12 months) 


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Principal investigator:  
Christine H. Chung, M.D. 
Moffitt Cancer Center – Coordinating Center 
12902 USF Magnolia Drive, Tampa, FL 33612  
Email: Christine.Chung@Moffitt.Org 
Phone: 813-745-5431 
 
Participating Site Principal Investigators:  
Julie Bauman, M.D. 
University of Arizona 
1515 N. Campbell Ave, #1969C  
Tucson, AZ 85724 
jebauman@email.arizona.edu 
Phone: 520-626-4101 
Fax: 520-626-2225 
Nabil Saba, M.D. 
Winship Cancer Institute - Emory University  
1365 Clifton Rd. 
Atlanta, GA 30322 
NFSaba@emory.edu 
Phone: 404-778-1900  
Fax: 404-686-0283 
 
Lara Dunn, M.D. 
Memorial Sloan Kettering Cancer Center 
885 2nd Avenue, Rm 1004 
New York, NY  10017 
dunnl1@mskcc.org 
Phone: 646-888-4233 
Fax: 646- 888-4269 
 
Stuart J. Wong, M.D. 
Medical College of Wisconsin 
9200 W. Wisconsin Ave 
Milwaukee, WI 53226 
swong@mcw.edu 
Phone: 414-805-0803 
Fax: 414-805-4606 
 
 
IND Sponsor: Exempt 
 
Funding Support:  
Regeneron Pharmaceuticals, Inc. 
777 Old Saw Mill River Road 
Tarrytown, NY 10591 
 
1 
KEY ROLES 


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The incidence of cutaneous squamous cell carcinoma (CSCC) is increasing, and the estimated annual 
number of deaths due to CSCC is thought to be under reported.1 The major risk factor for development 
of CSCC is exposure to UV radiation, particularly for fair-skinned people in geographic locations with 
high levels of UV radiaton.2,3 In addition, chronic immunosuppression, advanced age, exposure to 
ionizing radiation, manufacturing chemicals, arsenic, chronic ulcers, and burn scars are also risk 
factors to develop CSCC.1,4 The majority of primary CSCC is treated surgically with or without post-
operative radiation therapy depending on the risk of recurrence, and more than 95% of the patients 
are cured.1,4,5  
 
Although it is a highly curable cancer, some patients present with metastasis or locally advanced 
CSCC that are no longer amenable to surgery or radiation therapy. Unfortunately these patients are 
no longer curable, and their only optieon is palliative therapy. Among these incurable patients, 
immunocompromised patients have even worse clinical outcomes. For example, the 2-year 
progression free survival of immunocompromised patients excluding solid organ transplantation is only 
27% in a retrospective study.6 In patients with no lymph node involvement but immunocompromised 
due to chronic lymphocytic leukemia, the locoregional failure rate is 36% even when they are treated 
aggressively with radiation postoperatively.7,8 Therefore, this patient population with an extremely poor 
prognosis needs improved treatment.   
 
While immunocompromised patients have the most need for novel treatment options, they are often 
excluded in clinical trials. Recently, the programmed cell death-1 (PD-1)/programmed cell death-ligand 
1 (PD-L1) axis was determined to play an important role as immune checkpoint. PD-1 is one of the 
clinically significant checkpoint molecules that has been shown to suppress T-cell function upon 
binding to its ligands, PD-L1 and PD-L2, which are expressed on tumor cells in both preclinical models 
and clinical settings of cancer patients undergoing immunotherapy.9,10 In addition to promising efficacy, 
PD-1 and PD-L1 inhibitors are overall safe and well tolerated in a subset of immunocompromised 
patients such as patients with HIV infection, and additional studies are currently ongoing.11,12 
Immunotherapy targeting PD-1 has become a promising therapeutic option in management of CSCC.4 
Cemiplimab-rwlc is one of the PD-1 inhibitors with the most efficacy and safety data in management 
of unresectable locally advanced or metastatic CSCC.4 With Cemiplimab-rwlc as a monotherapy in 
patients with metastatic CSCC, overall complete response rate is 7% and partial response rate is 41%. 
It also has a very favorable toxicity profile. Based on these efficacy and safety data, Cemiplimab-rwlc 
is now FDA approved for the treatment of patients with metastatic CSCC or locally advanced CSCC 
who are not amenable to curative surgery or curative radiation.13 However, immunocompromised 
patients were excluded in the Cemiplimab-rwlc trial, and the safety and efficacy of Cemiplimab-rwlc is 
unknown in this patient population with the most limited treatment options. 
 
Even though it is counter intuitive to use immunotherapeutic approaches to immunocompromised 
patients, the full mechanism of how PD-1 inhibitors exerts anti-tumor effects are still unknown. In 
addition, recent data suggest that tumors with high tumor mutation burden respond better to PD-1 
inhibitors because of increased presence of neoantigens.14,15 Chung, et al. evaluated 1,300 mucosal 
head and neck SCC, 2,386 lung SCC, and 289 CSCC for tumor mutation burden and found CSCC 
has the highest number of mutations per megabase among the squamous cell carcinomas from 
various organ sites.16 Therefore, it is important to evaluate the efficacy and toxicity of Cemiplimab-rwlc 
in immunocompromised CSCC patients. 
 
2 
INTRODUCTION: BACKGROUND INFORMATION AND 
SCIENTIFIC RATIONALE 
2.1 
BACKGROUND INFORMATION 


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It suggests that CSCC is expected to be extremely sensitive to PD-1 inhibiting agents. However, there 
is no efficacy data in any immunocompromised population due to exclusion of these patients in clinical 
trials using PD-1 inhibitors. This population specific data are required to fulfill the unmet need. 
 
 
 
 
 
Cemiplimab-rwlc has not been tested in pregnant women, and there is no information available on 
patients receiving Cemiplimab-rwlc while pregnant. There is the possibility of unforeseeable risk to 
both the pregnant woman and unborn child if exposed to Cemiplimab-rwlc during pregnancy.  
The most common side effects related to Cemiplimab-rwlc treatment are as follows: 
Possible side effects: 
Very Common (10% or more of patients):  
o Fatigue  
o Rash 
o Nausea 
Common (1 to ≤10% of patients):  
o Arthraligia (joint pain) 
o Diarrhea  
o Decreased appetite 
o Asthenia (weakness or lack of energy) 
o Myalgia 
o Vomiting 
o Itching 
o Underactive or overactive thyroid gland (which can cause tiredness, constipation, hair 
loss, sensitivity to heat or cold temperatures, mood changes, sweating, muscle aches, a 
fast heartbeat or weight changes) 
o Damage to the liver (from inflammation) that does not cause symptoms, but does cause 
an abnormal result on a blood test of liver function 
o Fever 
o Anemia (low red blood cells that can cause tiredness, physical weakness or lack of 
energy) 
o Dry mouth 
o Headache 
o Flu-like illness 
o Swelling of an arm or leg 
o Constipation 
o Cough 
o Shortness of breath 
o Insomnia (trouble sleeping) 
o Pneumonitis (inflammation of the lung) which may be life-threatening or may lead to 
death 
2.2 
RATIONALE 
2.3 
POTENTIAL RISKS AND BENEFITS 
2.3.1 
KNOWN POTENTIAL RISKS 


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o Abdominal pain 
o Low white blood cells (that can make it more likely to get an infection)  
o Chills 
o Dry Skin 
o Stomatitis (inflammation of mouth and lips) 
o Decreased weight  
o Dehydration 
o Infusion reactions  
o Muscle spasms 
o Back pain 
o Dizziness 
o Low phosphate in the blood (that does not cause symptoms but causes an abnormal 
blood test) 
o Blurry vision 
Uncommon (≤ 1% of patients) but serious:  
o Encephalomyelitis (inflammation of the brain), which may result in severe memory loss 
and occasionally death.  
o Myasthenia gravis, a disease that causes muscle weakness  
o Colitis, an inflammation of the colon  
o Bronchospasm, a narrowing of air passages in the lungs causing shortness of breath 
o Diabetic ketoacidosis, a severe complication of diabetes (high blood sugar) where the 
body makes too much acid in the blood. 
As of January 2017, in all patients treated in all studies with Cemiplimab-rwlc, there were 5 deaths    
associated with Cemiplimab-rwlc. One patient died from encephalomyelitis (inflammation of the 
brain), one patient died from an unknown cause, two patients died from liver failure (including one 
with liver cancer), and one patient died from Toxic Epidermal Necrolysis (a type of severe skin 
reaction).   
There are additional potential immune-related side effects from Cemiplimab-rwlc that may be serious 
and require corticosteroid treatment and interruption or discontinuation of treatment. While some of 
these side effects have been seen in patients treated with Cemiplimab-rwlc (also listed above), these 
side effects have been observed with other drugs that act on the immune system in a similar way.  It 
is important to contact your doctor immediately if you experience any of these symptoms:  
o Pneumonitis (inflammation of the lung): new or worsening cough, chest pain, or 
shortness of breath. 
o Colitis (inflammation of the colon): diarrhea, blood in stool or severe abdominal 
pain  
o Hepatitis (inflammation of the liver):  jaundice (yellowing of skin, mucus 
membranes or whites of eyes), severe nausea or vomiting, or easy bruising or 
bleeding  
o Hypophysitis (inflammation of pituitary gland which secretes hormones to control 
several body processes): persistent or unusual headache, extreme weakness, 
dizziness or fainting, vision changes, or other changes due to an effect on your 
hormones 


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o Nephritis (inflammation of the kidney):  pain in pelvis, pain or burning during 
urination, frequent urination, blood in urine, vomiting, fever  
o Hyperthyroidism and Hypothyroidism (over or underactive thyroid gland):  
tiredness, weight gain or loss, hair loss, constipation, depression, irritability, 
muscle aches, intolerance to heat or cold 
o Uveitis (inflammation of the eye):   eye  redness, eye pain, light sensitivity, blurred 
vision, floaters, decreased vision  
o Skin changes: peeling of the skin over large areas of the body, rash, itching, skin 
blistering. 
o Mucositis (painful inflammation and ulceration of mucous membranes lining the 
digestive tract): painful sores in the mouth, tongue, nose or throat which can make 
it hard to eat or drink 
o Encephalitis (inflammation of the brain): headache, fever, tiredness, confusion, 
memory problems, sleepiness, seeing or hearing things that are not really there, 
seizures, stiff neck 
ALLERGIC REACTION RISK: 
There is a chance of an allergic reaction to the study drug. Low levels of doxycycline, an 
antibiotic, are used early in the manufacturing process of Cemiplimab-rwlc. The possibility 
exists of an allergic reaction in patients allergic to doxycycline.  
 
 
 
 
Cemiplimab-rwlc is one of the PD-1 inhibitors with the most efficacy and safety data in management 
of unresectable locally advanced or metastatic cutaneous SCC.4 With Cemiplimab-rwlc as a 
monotherapy in patients with metastatic CSCC, overall complete response rate is 7% and partial 
response rate is 41%. Based on these efficacy and safety data, Cemiplimab-rwlc is now FDA approved 
for the treatment of patients with metastatic CSCC or locally advanced CSCC who are not amenable 
to curative surgery or curative radiation.13 However, there is no efficacy data in any 
immunocompromised population due to exclusion of these patients in clinical trials using PD-1 
inhibitors. This population specific data are required to fulfill the unmet need. 
 
 
 
 
Primary Objective: Determine the overall response rate of Cemiplimab-rwlc in immunocompromised 
patients with unresectable locally recurrent and/or metastatic CSCC. 
 
Secondary Objective:  
1. Evaluate progression-free survival 
2. Evaluate overall survival 
3. Evaluate acute and late toxicities 
 
Exploratory Objective: 
1. Identify potential biomarkers related to response to Cemiplimab-rwlc in immunocompromised 
patients with unresectable locally recurrent and/or metastatic CSCC.  
2.3.2 
KNOWN POTENTIAL BENEFITS 
3 
OBJECTIVES  


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2. Evaluate overall response rate of underlying CLL in the CLL subset. 
 
 
 
 
 
 
This is a single arm phase II study to evaluate the efficacy of Cemiplimab-rwlc in immunocompromised 
patients with unresectable locally recurrent or metastatic CSCC.  
 
Eligible patients will be given Cemiplimab-rwlc 350 mg IV every 3 weeks. This will be administered 
until patients get severe side effects, disease progression, or for a period of 1 year (whichever point is 
reached first). 
 
A scan will be performed approximately every 9 weeks till the time that the patient is receiving the 
treatment. We plan to recruit 27 patients. 
 
 
 
 
 
 
 
Overall response rate of immunocompromised patients with unresectable locally recurrent and/or 
metastatic cutaneous SCCHN. 
 
 
 
1. Progression-free survival 
2. Overall survival 
3. Acute and late immune-related and non-immune-related toxicities 
 
 
 
1. Predictive biomarkers of Cemiplimab-rwlc response in CSCC.  
2. Overall response rate of underlying CLL in the CLL subset. 
 
 
 
 
 
1. Histologically confirmed diagnosis of invasive CSCC. 
   
Notes: Patients with mixed histologies (eg, sarcomatoid, adenosquamous) generally will not 
be eligible. Patients with mixed histology in which the predominant histology is invasive CSCC 
(with only a minimal component of mixed histology) may be eligible, after communication with 
4 
STUDY DESIGN AND ENDPOINTS 
4.1 
DESCRIPTION OF THE STUDY DESIGN 
4.2 
STUDY ENDPOINTS 
4.2.1 
PRIMARY ENDPOINT 
4.2.2 
SECONDARY ENDPOINTS 
4.2.3 
EXPLORATORY ENDPOINTS 
5 
STUDY ENROLLMENT AND WITHDRAWAL 
5.1 
PARTICIPANT INCLUSION CRITERIA 


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and approval from the each site principal investigator. 
 
2. Immunocompromised patients with invasive CSCC. Immunocompromised patients are defined 
as: 
a. History of HIV with CD4 counts >200 and no AIDS-defining illnesses. 
b. History of treated or active hematologic malignancies including lymphoma, Hodgkin’s 
disease, chronic lymphocytic leukemia, chronic myeloid leukemia, multiple myeloma, 
and myeloproliferative neoplasm. 
 
3. At least 1 lesion that is measurable by study criteria by RECIST 1.1. Externally visible 
cutaneous 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.  
 
4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.  
 
5. ≥18 years old. 
 
6. Hepatic function: 
a. Total bilirubin ≤3.0 x upper limit of normal (ULN)  
b. Transaminases ≤5.0 x ULN 
c. Alkaline phosphatase (ALP) ≤5.0 x ULN 
 
7. Renal function: Estimated creatinine clearance (CrCl) >30 mL/min. 
 
8. Bone marrow function: 
a. Hemoglobin ≥8.0 g/dL 
b. Absolute neutrophil count (ANC) ≥1.0 x 109/L 
c. Platelet count ≥50 x 109/L 
 
9. Ability to provide signed informed consent. 
 
10. Ability and willingness to comply with scheduled visits, treatment plans, laboratory tests, and 
other study-related procedure. 
 
11. Anticipated life expectancy >12 weeks. 
 
12. 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.  
 
 
 
1. Prior known allergy to Cemiplimab-rwlc.  
 
5.2 
PARTICIPANT EXCLUSION CRITERIA 


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2. Prior exposure to PD-1 or PD-L1 inhibitors. 
 
3. Prior exposure to idelalisib.  
 
Note: Patients who have previously been treated with idelalisib will be excluded from treatment 
with cemiplimab as a result of the safety findings for 3 patients with indolent lymphoma 
previously treated with idelalisib, a phosphatidylinositol 3-kinase (PI 3-K) inhibitor, in study 
R1979-ONC-1504. Following a single dose of cemiplimab monotherapy in each case, 2 
patients experienced severe stomatitis and/or skin reactions. The third patient experienced 
myositis and myasthenia gravis after 2 doses of cemiplimab. 
 
4. Immunocompromised patients due to the solid organ transplant, allogeneic bone marrow 
transplant, and/or autoimmune disease. 
 
5. Untreated brain metastasis(es) that may be considered active.  
 
Note: Patients with brain involvement of CSCC due to direct extension of invading tumor, rather 
than metastasis, may be allowed to enroll if they do not require greater than 10 mg prednisone 
daily. Patients with previously treated brain metastases may participate provided that the 
lesion(s) is (are) stable (without evidence of progression for at least 4 weeks on imaging 
obtained in the screening period), and there is no evidence of new or enlarging brain 
metastases, and the patient does not require any immunosuppressive doses of systemic 
corticosteroids for management of brain metastasis(es) within 4 weeks of first dose of 
Cemiplimab-rwlc. 
 
6. Immunosuppressive corticosteroid doses (> 10 mg prednisone daily or equivalent for >5 
consecutive days) within 4 weeks prior to the first dose of Cemiplimab-rwlc. 
 
Note: Patients who require brief course of steroids (eg, as prophylaxis for imaging studies due 
to hypersensitivity to contrast agents) are not excluded.  
 
7. 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 trial.  As an exception, known HIV infection is allowed. 
 
8. History of pneumonitis within the last 5 years. 
 
9. Grade ≥ 3 hypercalcemia at time of enrollment. 
 
10. 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. 
 
11. 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. 


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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. 
  
12. Patients who cannot discontinue the concurrent use of other chemopreventive agents such as 
5-FU, capecitabine, Efudex, imiquimod, acitretin are not allowed.  
 
13. Radiation therapy within 7 days of initial administration of Cemiplimab-rwlc or planned to occur 
during the study period.  
 
14. Breast feeding. 
 
15. Positive serum pregnancy test (a false positive pregnancy test, if demonstrated by serial 
measurements and negative ultrasound, will not be exclusionary) 
 
16. 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. 
 
17.  Any acute or chronic psychiatric problems that, in the opinion of the investigator, make the 
patient ineligible for participation. 
 
18. 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.   
 
 
 
 
 
 
Participants are free to withdraw from participation in the study at any time upon request. The study 
investigator or the funding source of the study (“Regeneron”) can remove participants from the study 
without their consent at any time for any reason including: 
 
• 
If any treatment-related Grade 4 adverse events (AE) develops during Cemiplimab-rwlc 
therapy.  
• 
If any clinically adverse event (AE), laboratory abnormality, or other medical condition or 
situation occurs such that continued participation in the study would not be in the best 
interests of the participant. 
5.4 
PARTICIPANT WITHDRAWAL OR TERMINATION 
5.4.1 
REASONS FOR WITHDRAWAL OR TERMINATION 


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• 
If the participant meets any exclusion criteria (either newly developed or not previously 
recognized) that precludes further study participation. 
• 
Extraordinary medical circumstances: If at any time the constraints of this protocol are 
detrimental to the patient’s health, the protocol treatment should be discontinued. 
• 
If patient develops progressive disease, then the patient will discontinue the protocol 
therapy. 
• 
If patient develops unacceptable toxicity, then the patient will discontinue the protocol 
therapy. 
 
The reason and date for patient removal from the study must be documented in the Case Report 
Form (CRF). 
 
The same procedures will be followed as those that would happen if participants decided to 
discontinue from the study. 
 
 
 
 
Every effort will be made to undertake protocol-specified safety follow-up procedures to capture 
AEs, serious adverse events (SAEs), and unanticipated problems. 
 
Those who discontinue protocol therapy early will be followed for response until progression and for 
survival for 1 year from the date of withdraw or termination.  
 
Patients removed from study for unacceptable adverse events will be followed until resolution or 
stabilization of the adverse event. 
 
 
 
 
This study may be temporarily suspended or prematurely terminated by the investigators.  
Circumstances that may warrant termination or suspension include, but are not limited to: 
 
• 
Determination of unexpected, significant, or unacceptable risk to participants. 
• 
Demonstration of efficacy that would warrant stopping. 
• 
Insufficient compliance to protocol requirements. 
• 
Data that is not sufficiently complete and/or evaluable. 
• 
Determination of futility. 
 
If the study is prematurely terminated or suspended, the PI will promptly inform the IRB and will 
provide the reason for the termination or suspension. 
 
Study may resume once concerns about safety, protocol compliance, data quality are addressed 
and satisfy the PI and IRB. 
 
 
 
 
5.4.2 
HANDLING OF PARTICIPANT WITHDRAWALS OR TERMINATION 
5.5 
PREMATURE TERMINATION OR SUSPENSION OF STUDY 
6 
STUDY AGENT 
6.1 
STUDY AGENT(S) AND CONTROL DESCRIPTION 


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Cemiplimab-rwlc will be supplied by Regeneron Pharmaceuticals, Inc. Cemiplimab-rwlc will be 
shipped at a temperature of 2º to 8ºC to the investigator or designee at regular intervals or as 
needed during the study.  At specified time points during the study (eg, interim site monitoring 
visits), at the site close-out visit, and following drug reconciliation and documentation by the site 
monitor, all opened and unopened study drug will be destroyed or returned to Regeneron 
Pharmaceuticals, Inc.or designee. 
 
 
 
 
Cemiplimab-rwlc will be supplied as a liquid in sterile, single-use vials. Each vial will contain 
Cemiplimab at a concentration of 25 mg/mL or 50 mg/mL. 
 
 
 
Cemiplimab-rwlc will be refrigerated at the site at a temperature of 2º to 8ºC, and refrigerator 
temperature will be logged daily. Further storage instructions will be provided in the pharmacy 
manual.  
 
 
 
Visually inspect for particulate matter and discoloration prior to administration. Cemiplimab-rwlc is 
a clear to slightly opalescent, colorless to pale yellow solution that may contain trace amounts of 
translucent to white particles. Discard the vial if the solution is cloudy, discolored or contains 
extraneous particulate matter other than trace amounts of translucent to white particles. 
 
Preparation: 
• 
Do not shake. 
• 
Withdraw 7 mL from a vial and dilute with 0.9% Sodium Chloride Injection, USP or 5% 
Dextrose Injection, USP to a final concentration between 1 mg/mL to 20 mg/mL. 
• 
Mix diluted solution by gentle inversion. Do not shake. 
• 
Discard any unused medicinal product or waste material. 
 
 
 
A pharmacist or other qualified individual will be identified at each site to prepare Cemiplimab-rwlc 
for administration. The planned dose and schedule of Cemiplimab-rwlc is 350 mg IV over 
approximately 30 minutes every 21 days (+/- 3 days).   
 
Storage of Infusion Solution: 
• 
Store at room temperature up to 25 oC (77 oF) for no more than 8 hours from the time of 
preparation to the end of the infusion or at 2 oC to 8 oC (36 oF to 46 oF) for no more than 24 
hours from the time of preparation to the end of infusion. 
• 
Allow the diluted solution to come to room temperature prior to administration. 
• 
Do not freeze. 
 
6.1.1 
ACQUISITION 
6.1.2 
FORMULATION, APPEARANCE, PACKAGING, AND LABELING 
6.1.3 
PRODUCT STORAGE AND STABILITY 
6.1.4 
PREPARATION 
6.1.5 
DOSING AND ADMINISTRATION 


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Administration: 
• 
Administer by intravenous infusion over 30 minutes through an intravenous line containing 
a sterile, in-line or add-on 0.2 micron to 5-micron filter. 
 
 
 
Cemiplimab-rwlc  will be administrated intravenously.  
 
 
 
 
Cemiplimab-rwlc is administered as a flat dose of 350 mg IV over approximately 30 minutes every 
21 days (+/- 3 days).  
 
 
 
Patients will remain on the dosage of Cemiplimab-rwlc throughout the course of study treatment.  
Dose reduction is not allowed. The dose will be held until the resolution of the adverse events as 
below.   
 
Adverse events (AEs) are to be reported according to the National Cancer Institute Common 
Terminology Criteria for Adverse Events (NCI-CTCAE) version 5. Patients who experience grade ≥3 
treatment-related toxicity (excluding laboratory abnormalities that are considered clinically 
insignificant) that is not otherwise specified in the protocol will be required to temporarily discontinue 
treatment with Cemiplimab-rwlc. Such patients may be considered for resumption of treatment once 
the toxicity resolves to grade 1 or baseline, or when the toxicity is stable and manageable through 
supportive/medical therapy (eg, grade 3 hypertension that can be controlled with addition of a second 
anti-hypertensive agent) per the CTCAE version 5. 
 
Holding of treatment due to an AE or a missed visit if a patient is hospitalized is not a violation. If a 
patient is able to come in for a study visit according to the visit schedule, but does not receive 
Cemiplimab-rwlc, the visit should be entered into the database. The protocol assessments required 
at the visit (ie, labs, physical exam) should still be completed as far as possible and the data entered 
at the appropriate visit in the electronic case report form (CRF). If the patient is not able to come in 
for a study visit, according to the study schedule, the visit should be skipped. If a scan was missed 
as part of the skipped visit, the response assessment will be performed prior to resuming treatment 
and subsequent scans will be performed in line with the original schedule. 
 
Upon occurrence of a study treatment-related event at any time on the study, resumption of treatment 
after resolution or stabilization of the condition is allowed at the discretion of the investigator if 
resuming treatment is thought to be in the best interest of the patient, with the exception of the 
following categories: 
 
• 
Patients with events that require Cemiplimab-rwlc to be discontinued for more than 84 days 
from last scheduled dose. 
• 
Patients with grade ≥2 uveitis. Patients with grade 2 uveitis will generally be discontinued from 
study treatment, unless there is resolution to grade ≤1 AND discussion with and approval by 
the site principal investigators. All patients with grade ≥3 uveitis will be permanently 
discontinued from study treatment. 
 
After other AEs, resumption of treatment may be at the initial dose level. A patient who does not 
6.1.6 
ROUTE OF ADMINISTRATION 
6.1.7 
STARTING DOSE AND DOSE ESCALATION SCHEDULE 
6.1.8 
DOSE ADJUSTMENTS/MODIFICATIONS/DELAYS 


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tolerate Cemiplimab-rwlc will be removed from the study.  Refer to Appendix 1 for additional 
management guidelines for immune-related toxicities. 
 
 
 
Patients will be treated for 1 year (17 cycles) unless they have disease progression, intolerable 
toxicities or withdraw consents. 
 
 
 
Cemiplimab-rwlc will be administered at the study site and recorded on the electronic CRF. All dosing 
records for each patient will be kept by the site. All drug compliance records must be kept current 
and must be made available for inspection by the lead site and regulatory agency inspectors.  
 
 
 
Not Applicable 
 
 
 
All drug accountability records must be kept current. The investigator must be able to account for all 
opened and unopened study drug. These records should contain the dates, quantity, and study 
medication dispensed to each patient, returned from each patient (if applicable), and disposed of at 
the site or returned to Regeneron Pharmaceuticals Inc. All accountability records must be made 
available for inspection by the lead site and regulatory agency inspectors; photocopies must be 
provided to the lead site at the conclusion of the study.  
 
 
. 
 
 
 
 
Not Applicable 
 
 
 
Standard of care procedures obtained during the study: 
• 
Medical history.  
• 
Medication history.  
• 
Physical examination. 
• 
Radiographic, photographic, or other imaging assessments.  
• 
Laboratory evaluations.  
• 
Assessment of therapy adherence.  
 
 
6.1.9 
DURATION OF THERAPY 
6.1.10 
TRACKING OF DOSE 
6.1.11 
DEVICE SPECIFIC CONSIDERATIONS 
6.2 
STUDY AGENT ACCOUNTABILITY PROCEDURES 
7 
STUDY PROCEDURES AND SCHEDULE 
7.1 
STUDY PROCEDURES/EVALUATIONS 
7.1.1 
STUDY-SPECIFIC PROCEDURES 
7.1.2 
STANDARD OF CARE STUDY PROCEDURES 
7.2 
LABORATORY PROCEDURES/EVALUATIONS 


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Table 1. Clinical laboratory tests 
 
Category 
Tests 
Laboratory tests 
CBC w/differential (hemoglobin, hematocrit, WBC with 
differential count, platelet count) 
CMP (Sodium, potassium, bicarbonate, chloride, BUN, 
creatinine, total bilirubin, ALT, AST).  
Magnesium 
INR (only as part of the screening assessment or if clinically 
indicated) 
Amylase, lipase 
Hepatitis testing for only research purposes will not be 
performed, but documented if the status is known. 
HIV CD4 count as a standard of care 
Pregnancy test 
Serum or urine β-hCG ( for  women of childbearing potential) 
Thyroid panel  
TSH and free T4 
 
ALT= alanine aminotransferase, AST=aspartate aminotransferase, β-hCG = beta-human chorionic 
gonadotropin, BUN=blood urea nitrogen CBC=complete blood count, CMP=comprehensive metabolic 
panel, INR = International Normalized Ratio, TSH= thyroid stimulating hormone, T4 = thyroxine, 
WBC=white blood cells.  
 
 
 
 
Patients from the parent study will be eligible for participation on an optional basis in a tissue biomarker 
study and the blood collection for the biomarker correlative study. 
 
In all study participants, submission of archived diagnostic formalin fixed paraffin embedded (FFPE) 
tumors obtained at any time prior to Cemiplimab-rwlc treatment is required. Additionally, tumor tissue 
will be obtained from the most accessible locations for a biopsy prior to initiation and at the end of 
Cemiplimab-rwlc therapy. These biopsies for only research purposes are OPTIONAL. Any metastatic 
cancer tissue obtained during the study (including but not limited to excisional, core biopsies, surgical 
specimens, etc.) will be subject to additional molecular studies in the future. 
 
PROPOSED BIOMARKER EVALUATIONS  
 
7.2.2.1 
Determination of the genomic landscape to determine tumor mutation burden 
The archived FFPE primary tumors (and subsequent metastatic tumors if available) will be analyzed 
by whole exome sequencing, and the comprehensive genomic landscape and tumor mutation burden 
will be assessed.    
 
7.2.2.2 
Evaluation of the Tumor Immune Microenvironment 
Intact immune system is critical for tumor surveillance. Comprehensive evaluation of tumor immune 
microenvironment has not been fully characterized. An innovative methodology, multiplex immune-
histochemical (mIHC) staining, allows the analysis of an array of markers from limited sample 
specimens. The evaluation of a complex cellular microenvironment is best accomplished using mIHC 
which enables simultaneous detection and measurement of multiple protein antigens on the same 
tissue section allowing accurate classification of cells as well as enumeration and quantification of 
7.2.1 
CLINICAL LABORATORY EVALUATIONS 
7.2.2 
OTHER ASSAYS OR PROCEDURES 


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protein signal. This is accomplished by using sequential steps of primary antibody application, 
scanning the image, and then antibody stripping. The process is repeated using each antibody target. 
The result is that up to 20 protein targets can be visualized. This complex staining can then be analyzed 
by imaging systems such as the Aperio scanning system. Image analysis software can then be applied 
to enumerate cells and quantify signal. Complex analysis can determine cellular densities and also 
measure co-localized targets. The multiplexing will encompass evaluation of antigen presenting cells, 
T cells, B cells, macrophages, and tumor cells. The goal is to link a comprehensive clinical 
characterization and immune microenvironment assessment and to correlate these with Cemiplimab-
rwlc treatment response and survival.  
 
7.2.2.3 
Detection of Circulating Tumor DNA in Plasma and Its Association With Cemiplimab-
rwlc response  
Determination of early response to Cemiplimab-rwlc by conventional imaging studies can be difficult. 
Circulating tumor DNA in pre- and post-treatment plasma has been shown to track with the disease 
burden.17 We will determine the presence of a unique genomic alteration found in each patient based 
on the whole exome sequencing of their tumor and identify the presence of the alterations in circulating 
tumor DNA. Quantity of circulating tumor DNA in the plasma compared with at pre-treatment and at 
end of treatment will be correlated with the response determined by the imaging studies.       
 
 
Tissue specimens will be handled and stored according to the Laboratory Manual. 
 
Tissue/Specimen Submission  
Tumor tissue samples will be collected at pre- and post-treatment. The tumor tissue samples will be 
submitted to the Moffitt Tissue Core for banking and translational research.  
 
Pre-treatment formalin-fixed paraffin-embedded (FFPE) archived tumor samples (MANDATORY) 
 
Any archived tumor tissue (except FNA cell blocks) obtained before Cemiplimab-rwlc is allowed. An 
FFPE tumor block should be submitted with the submission form. A Pathology Report and one 
hematoxylin and eosin-stained slide documenting that the submitted block or unstained slides contain 
tumor should also be submitted with the tissue. The report and hematoxylin and eosin-stained slide 
must include the protocol number and patient’s case number. The patient’s name and/or other 
identifying information should be removed from the report. The surgical pathology numbers and 
information must NOT be removed from the report.  
 
Pre- and post-treatment tumor biopsy (Day -21 to 0 before Cemiplimab-rwlc and at the End of 
Treatment visit; OPTIONAL) 
 
The pre- and post-treatment tumor biopsy can be obtained from the primary site, lymph node 
metastasis, or other safely accessible site metastases as a punch biopsy or a core needle biopsy: one 
punch or core in formalin and the second punch or core in liquid nitrogen (or dry ice/ethanol slurry). 
The biopsy sample should be prepared: 1) as a formalin-fixed paraffin-embedded tumor block and 2) 
as a flash frozen sample in liquid nitrogen (or dry ice/ethanol slurry). The frozen specimens can be 
stored at -80°C (-70°C to -90°C).  
 
CORRELATIVE WITH BLOOD 
Blood samples must be submitted with the submission form documenting the date of collection of the 
sample; the protocol number, the patient’s case number, time point of study, and method of storage 
(for example, stored at -80°C). The frozen specimens can be stored at -80°C (-70°C to -90°C).  
7.2.3 
SPECIMEN PREPARATION, HANDLING, AND STORAGE 
SPECIMEN PREPARATION, HANDLING, AND STORAGE 


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The blood samples should be processed as detailed in the Laboratory Manual.  
 
In brief, 
 
1 x 10 ml Lavender EDTA tube and 1 x 8.5 ml LBgard tube of blood will be generated from each 
clinical event. The samples will be processed and shipped according to the Laboratory Manual. 
 
Clinical events: 
1. Pre-therapy (Anytime between Day -21 and Cycle 1 Day 1) 
2. Cycle 3 Day 1 +/- 7 days 
3. Cycle 6 Day 1 +/- 7 days 
4. Cycle 9 Day 1 +/- 7 days 
5. Cycle 12 Day 1 +/- 7 days 
6. End of treatment +/- 7 days 
7. End of study +/- 7 days 
 
Collection procedure:  
• 
Draw one 10 ml Lavender EDTA tube and one 8.5 ml LBgard Blood Tube. 
• 
Draw the EDTA tube first and then LBgard Blood Tube second. 
• 
Completely fill the LBgard Blood Tube. 
• 
When draw the LBgard Blood Tube, follow the steps below to avoid possible backflow of 
chemical additives from the tube. 
o Place the subject’s arm in a downward position. 
o Hold tube in vertical position, below the donor’s arm during blood collection. 
o Release tourniquet as soon as blood starts to flow into tube. 
o Ensure that tube additives do not contact stopper or end of needle during venipuncture. 
• 
Ensure that the blood has stopped flowing into the tube before removing the tube from the 
holder. 
• 
Immediately after blood draw, gently invert the LBgard Blood Tube ten times. 
• 
The blood samples should be processed within 2 hours from collection. 
• 
If the blood samples cannot be processed within 2 hours from collection due to lack of 
institutional facility, draw the second LBgard blood tube in place of the EDTA tube and 
ship without any processing within 24 hours in room temperature. 
 
Table 2. Specimen collection summary for correlative studies (Samples can be batched and 
sent in one shipment)  
 
Specimens 
taken 
from 
patient: 
Collected when: 
Stored as: 
Archived paraffin-embedded 
tissue of the primary tumor 
taken any time before initiation 
of Cemiplimab-rwlc treatment 
(Mandatory) 
Pre-treatment 
Paraffin-embedded 
tissue block. 
Refer to the 
Laboratory Manual. 
Fresh frozen tissue of the 
primary or metastatic tumor 
taken before initiation of 
Cemiplimab-rwlc treatment (for 
research purposes only: 
OPTIONAL) 
Pre-treatment 
Frozen tumor in a 2 
mL cryovial. 
Refer to the 
Laboratory Manual. 
A paraffin-embedded tissue of 
Pre-treatment and Post-treatment 
Paraffin-embedded 


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the primary or metastatic tumor 
(for research purposes only: 
OPTIONAL) 
taken:  
1) during Day -21 to 0 before Cycle 
1 Day 1 of Cemiplimab-rwlc, and 
2) at the End of Treatment visit 
tissue block. 
Refer to the 
Laboratory Manual. 
Fresh frozen tissue of the 
primary or metastatic tumor (for 
research purposes only: 
OPTIONAL) 
Post-treatment taken at the End of 
Treatment visit 
Frozen tumor in a 2 
mL cryovial. 
Refer to the 
Laboratory Manual. 
PLASMA: 18.5 mL of 
anticoagulated whole blood in 
EDTA tube (purple/ lavender 
top) and LBgard tube 
Pre-treatment  
and 
post-treatment taken:  
1) during Day -21 to 0 before 
Cemiplimab-rwlc   
2) Cycle 3 Day 1 +/- 7  
3) Cycle 6 Day 1 +/- 7  
4) Cycle 9 Day 1 +/- 7 
5) Cycle 12 Day 1 +/- 7 
6) End of Treatment +/- 7 days 
7) End of Study +/- 7 days 
Frozen plasma 
samples 3 to 5 
labeled 2 ml size 
Nunc cryovial with 1.5 
ml of plasma each. 
Refer to the 
Laboratory Manual. 
PBMC: 18.5 mL of 
anticoagulated whole blood in 
EDTA tube (purple/ lavender 
top) and LBgard tube. Collect 
PBMC and buffy coat after 
collecting plasma. 
Pre-treatment  
and 
post-treatment taken:  
1) during Day -21 to 0 before 
Cemiplimab-rwlc   
2) Cycle 3 Day 1 +/- 7  
3) Cycle 6 Day 1 +/- 7  
4) Cycle 9 Day 1 +/- 7 
5) Cycle 12 Day 1 +/- 7 
6) End of Treatment +/- 7 days 
7) End of Study +/- 7 days 7 days 
3 to 5 labeled 2 ml 
size Nunc cryovial 
with ~2-3 million of 
PBMC cells in each 
cryovial. Refer to the 
Laboratory Manual. 
 
 
 
The laboratory work will be done at the Moffitt Cancer Center. The samples will be analyzed for 
correlative studies.  Submit materials for translational research as detailed in the lab manual.  
 
 
 
 
 
Screening Visit (Day -28 to -0) 
Before performing any procedures or assessments, the nature of the study and the potential risks 
associated with the trial will be explained to all subject candidates and written informed consent will be 
obtained. Once informed consent has been obtained (within 8 weeks of first dose of study drug), the 
following procedures and evaluations will be performed: 
 
• 
Verify inclusion/exclusion criteria  
• 
Measurable disease by RECIST 1.1 using computerized tomography/magnetic resonance 
imaging (CT/MRI) or photographs of pertinent sites involved with disease. 
• 
Obtain vital signs (systolic and diastolic BP, HR, RR, and body temperature) and weight. BP, 
HR, and RR will be obtained after subjects have been resting for 5 minutes. 
7.2.4 
SPECIMEN SHIPMENT 
7.3 
STUDY SCHEDULE 
7.3.1 
SCREENING 


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• 
Perform a comprehensive physical examination (including a neurological evaluation). 
• 
Collect blood samples for laboratory testing and pregnancy test if indicated.  
• 
Collect urine or serum sample for β-hCG pregnancy testing from all women of childbearing 
potential. 
• 
Record all prior and concomitant medication use (prescription and nonprescription 
medications as well as transfusions). 
• 
Plan for obtaining tumor tissue.  
• 
Collect research blood sample (may be collected on Cycle 1 Day 1 prior to therapy) 
 
The screening form must be completed for all subjects screened, providing reasons for screen failure 
when applicable. 
 
 
 
Enrollment/Baseline: Cycle 1 Day 1 (cycle = 3 weeks) 
 
The baseline assessment can be performed on Cycle 1 Day 1 (C1D1), prior to treatment.  
 
Clinical and laboratory assessments are valid if obtained within 72 hours of baseline assessment.  
• Obtain informed consent or verify previously obtained during screening signed informed consent 
form. 
• Verify inclusion and exclusion criteria. 
• Obtain laboratory tests. 
• Confirm negative urine/serum pregnancy test. 
• Obtain demographic information, medical history, medication and social history. 
• Evaluate ECOG performance status.  
• Obtain vital signs. 
• Record all concomitant medication use.  
• Perform a comprehensive physical examination.  
• Establish new baseline tumor assessments (selection of target and non-target lesions) based 
upon scans taken (CT and/or MRI) or lesions photographed unless performed within 4 weeks. 
• Educate about potential AEs and SAEs. Encourage early recognition and reporting.  
• Obtain tumor tissue (should be done prior to initiation of therapy).  
• Collect research blood sample (only if not collected during screening) 
 
 
 
On Treatment Visits 
Study participants will be seen every 3 weeks before each cycle (Cycle 1 Day 1, Cycle 2 Day 1, etc).  
 
In each scheduled visit we will: 
• 
Obtain vital signs. 
• 
Record all concomitant medication use.  
• 
Perform a comprehensive physical examination.   
• 
Obtain laboratory tests.  
• 
Assess for AEs and SAEs.  
• 
Assess compliance with the medication.  
• 
Assess survival.  
• 
Collect research blood sample (Cycles 3, 6, 9 and 12 only) 
• 
Cemiplimab administration  
7.3.2 
ENROLLMENT/BASELINE 
7.3.3 
TREATMENT VISITS 


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Diagnostic imaging 
Diagnostic imaging of affected and suspected sites (CT, MRI and/or photographs) will be done at Day 
1 of cycles 3, 6, 9, 12, and 15 (or between Day 15-21 of the prior cycle) in all patients. Diagnostic 
imaging will continue to be done every 2 months thereafter or as clinically indicated otherwise. 
 
 
 
 
 
An End of Treatment (EOT) visit will be performed for all subjects.  At the end of treatment (30 days 
after last Cemiplimab-rwlc dose) the following data will be collected: 
 
• 
Obtain vital signs. 
• 
Record all concomitant medication use.  
• 
Perform a comprehensive physical examination.   
• 
Obtain laboratory tests.  
• 
Assess for AEs and SAEs.  
• 
Assess compliance with the medication.  
• 
Assess survival.  
• 
Optional fresh tumor biopsy (in order to accommodate scheduling, this biopsy may occur up to 
an additional 30 days beyond the EOT visit). 
• 
Diagnostic imaging of affected and suspected sites (CT, MRI and/or photographs), if not 
performed within the last 8 weeks. 
• 
Collect research blood sample 
 
 
 
 
 
To assess for late toxicities, at 6 months and 12 months after EOT patients will return for a 
physical exam and labs, unless the patient has enrolled in hospice care or is otherwise 
unwilling/unable to return to clinic.   
 
For this protocol, all patients, including those who discontinue protocol therapy early, will be 
followed for response until progression and for survival for 2 years from the start of treatment. All 
patients must also be followed through completion of all protocol therapy. Patients removed from 
study for unacceptable adverse events will be followed until resolution or stabilization of the 
adverse event.  Follow-up for survival will be performed every 90 days (± 2 weeks) from the end of 
treatment visit. 
 
Research blood collection to be performed at the end of study (2 years after initiation of study 
treatment). 
 
 
 
 
 
 
Unscheduled visits may be related but not limited to development of Cemiplimab-rwlc toxicities. In that 
7.3.4 
END OF TREATMENT VISIT 
7.3.5 
FOLLOW-UP 
7.3.6 
UNSCHEDULED VISIT 


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case the Grade of toxicity will be documented and the medication dose will be adjusted as per 
protocol. All unscheduled visit will be documented in the patients chart.  


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Table 3. Schedule of events   
Phase 
Screen 
Experimental phase 
Cycle (21 days) 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 11 12 13 14 15 16 17 
EOTk 
Follow-Up 
Daya 
-28 to -0 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
30 
Q3 months 
Assessments 
Informed consentb 
Xc  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion 
Xc  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographic data 
Xc  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
Xc  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ECOG 
Xc  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signsd 
Xc  
Xc 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xm 
Physical exame 
Xc  
Xc 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xm 
Laboratory testsf 
Xc  
Xc 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xm 
Pregnancy testg 
Xc  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Imaging studies (CT/MRI)h 
Xc  
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
Xl 
 
Mandatory research blood 
collection 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
 
 
 
X 
Xn 
Tumor collection 
Mandatory: 
- Archival 
 
Optional: 
- Fresh Tissue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Optional: 
- Fresh Tissue 
 
 
Cemiplimab Administration 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Concomitant medsi 
X 
X 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
AEs/SAEsj 
 
Throughout 
X 
 
Survival 
 
Throughout 
X 
X 
 
 
a: Efforts should be made to conduct study visits on the day scheduled (± 3 days). Clinical and laboratory assessments may be conducted anytime within 72 hours prior to the 
scheduled visit, unless otherwise specified in the Schedule of Visits and Procedures. 
b: Informed consent may be taken up to 8 weeks prior to C1D1. 
c: The baseline assessment can be performed on Cycle 1 Day (C1D1), prior to treatment. Clinical and laboratory assessments are valid if obtained within 72 hours of baseline 
assessment.  
d: Assessments will include vital signs (resting BP, HR, RR, and body temperature and weight. BP, HR, and RR will be obtained after subjects have been resting for 5 minutes. 
7.3.7 
SCHEDULE OF EVENTS TABLE 


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e: Comprehensive physical examination (including a neurological evaluation). 
f: Laboratory tests include: CBC w/differential, CMP, ALT, AST, magnesium, amylase, lipase, TSH, and if clinically indicated INR.   
g: Serum or urine, in women of childbearing potential only. 
h: Baseline images to include CT/MRI of head /neck/chest/abdomen/pelvis and other areas of known disease or clinical measurements and/or photographs of superficial 
tumors.  On treatment imaging will include only areas of known disease plus any areas of newly suspected disease. 
i: All concomitant prescription medications taken during study participation will be recorded on the case report forms (CRFs). 
j: AEs/SAEs will be assessed during each visit clinically and based on laboratory data. Patients will be encouraged to report AEs/SAEs at the earliest recognition via the phone 
between the visits.  
k: End of Treatment visit is to occur 30 days after the last dose of Cemiplimab-rwlc therapy ±7 days.  If the subject is unable or unwilling to return to clinic this visit can be 
conducted via a telephone call.  
l: May be omitted if performed within the last 8 weeks. 
m: Physical exam and labs required at 6 months and 12 months after EOT only to assess for late AEs, unless the patient has enrolled in hospice care or is otherwise 
unwilling/unable to return to clinic.   
n: Research blood collection to be performed at the end of study (2 years after initiation of study treatment).


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All concomitant prescription medications taken during study participation will be recorded on the case 
report forms (CRFs).  
 
All additional local therapies for metastatic lesions (including, but not limited to EBRT, surgery, 
embolization, ethanol injections, etc.) will be recorded on CRFs.  
 
• 
Steroid: Treatment with oral/IV corticosteroids (>10mg daily prednisone equivalent) is not 
allowed for non-immunological toxicities.  Treatment with oral/IV corticosteroids (>10mg daily 
prednisone equivalent) for immunological toxicities is permitted as detailed in the dose 
modification sections. 
• 
Use of corticosteroids (≤ 10 mg daily prednisone equivalents) is allowed. Inhaled or topical 
steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted 
in the absence of active autoimmune disease. 
• 
Palliative radiation therapy is allowed to non-target lesions at the discretion of the treating 
physician.  As concurrent radiotherapy and Cemiplimab-rwlc have not been formally evaluated, 
in cases where palliative radiotherapy is required for a tumor lesion, then Cemiplimab-rwlc 
should be withheld for at least 1 week before, during, and 1 week after radiation. Subjects 
should be closely monitored for any potential toxicity during and after receiving radiotherapy. 
• 
Surgical resection of new and non-target cutaneous lesions that are <10mm is allowed at the 
discretion of the treating physician. Surgical resection of target lesions is only permissible if all 
previously identified target lesions are rendered operable. For guidance on the impact on 
response assessment refer to the composite response criteria found in Appendix 2. 
 
 
 
 
 
Not Applicable.  
 
 
 
• 
Steroid: Treatment with oral/IV corticosteroids (>10mg daily prednisone equivalent) is not 
allowed for non-immunological toxicities.  Treatment with oral/IV corticosteroids (>10mg daily 
prednisone equivalent) for immunological toxicities is permitted as detailed in the dose 
modification sections. 
 
 
 
Not Applicable. 
 
 
7.4 
CONCOMITANT MEDICATIONS, TREATMENTS, AND PROCEDURES 
7.5 
JUSTIFICATION FOR SENSITIVE PROCEDURES 
7.5.1 
PRECAUTIONARY MEDICATIONS, TREATMENTS, AND PROCEDURES 
7.6 
PROHIBITED MEDICATIONS, TREATMENTS, AND PROCEDURES 
7.7 
PROPHYLACTIC MEDICATIONS, TREATMENTS, AND PROCEDURES 
7.8 
RESCUE MEDICATIONS, TREATMENTS, AND PROCEDURES 


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Immuno-oncology agents are associated with AEs that can differ in severity and duration than AEs 
caused by other therapeutic classes. Cemiplimab-rwlc is considered an immune-oncology agent in 
this protocol. Early recognition and management of AEs associated with immuno-oncology agents 
may mitigate severe toxicity. Management Algorithms have been developed to assist investigators in 
assessing and managing the following groups of AEs: 
• 
Gastrointestinal 
• 
Renal 
• 
Pulmonary 
• 
Hepatic 
• 
Endocrinopathy 
• 
Skin 
• 
Neurological 
The above algorithms can be found in Appendix 1 
 
Hypersensitivity infusion reactions should be reported to the site principal investigator and 
Regeneron Pharmaceuticals, Inc. within 24 hours of the event regardless of grade. The following AE 
terms constitute hypersensitivity infusion reactions: 
• 
Allergic reaction 
• 
Anaphylaxis 
• 
Cytokine release syndrome 
• 
Serum sickness 
• 
Infusion reactions 
• 
Infusion-like reactions 
 
Management of infusion reactions. 
Infusion reaction treatment guidelines are summarized in Table 4 below.  Institutional standards for 
infusion reactions may be followed if the treating physician deems them acceptable for this protocol. 
 
Table 4. Management of infusion reaction  
Grade 1 
Mild reaction 
Increase monitoring of vital signs as medically indicated 
until the patient is deemed medically stable in the 
opinion of the investigator 
None 
Grade 2 
Requires infusion 
interruption but 
responds promptly 
to symptomatic 
treatment (i.e., 
antihistamines, 
NSAIDS, narcotics, 
IV fluids); 
prophylactic 
medications 
indicated for ≤ 24 
hours 
Stop infusion and monitor symptoms.  
Additional appropriate medical therapy may include but 
is not limited to: 
• 
IV fluids 
• 
Antihistamines 
• 
NSAIDS 
• 
Acetaminophen 
• 
Narcotics 
Increase monitoring of vital signs as medically 
indicated until the patient is deemed medically stable in 
the opinion of the investigator. 
If symptoms resolve within one hour of stopping 
drug infusion, the infusion may be restarted at 50% of 
the original infusion rate.  
Otherwise, dosing will be held until symptoms 
resolve, and the patient should be premedicated for the 
next scheduled dose. 
Patients who develop Grade 2 toxicity despite 
adequate premedication should be permanently 
discontinued from further trial treatment administration.  
Subject may be 
premedicated 1.5h 
(+ 30 minutes) prior 
to infusion of 
cemiplimab with: 
• Diphenhydramin
e 50 mg PO (or 
equivalent dose 
of antihistamine) 
• Acetaminophen 
500-1000 mg PO 
(or equivalent 
dose of 
antipyretic) 


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Grade 3 or 4 
Grade 3: 
Prolonged (i.e., not 
rapidly responsive 
to symptomatic 
medications and/or 
brief interruption of 
infusion); recurrence 
of symptoms 
following initial 
improvement; 
hospitalization 
indicated for other 
clinical sequelae 
(e.g., renal 
impairment, 
pulmonary 
infiltrates) 
 
Grade 4:  
Life-threatening; 
pressor or 
ventilatory support 
indicated  
Stop infusion.  
Additional appropriate medical therapy may include but 
is not limited to: 
• 
IV fluids 
• 
Antihistamines 
• 
NSAIDS 
• 
Acetaminophen 
• 
Narcotics 
• 
Oxygen 
• 
Pressors 
• 
Corticosteroids 
• 
Epinephrine 
Increase monitoring of vital signs as medically 
indicated until the patient is deemed medically stable in 
the opinion of the investigator. 
Hospitalization may be indicated. 
Patient is permanently discontinued from further trial 
treatment administration. 
No subsequent 
dosing 
 
 
 
 
Cemiplimab-rwlc is an FDA approved drug for treatment of CSCC. Study participant may choose to 
continue Cemiplimab-rwlc as per standard of care if indicated upon study closure.  
 
 
 
 
 
 
Study participants will be monitored closely based on clinical, laboratory and imaging studies as 
outlined in study calendar (Table 3).  Patients will be educated and encouraged to report any AEs 
and SAEs promptly.  All AEs and SAEs will be graded according to CTCAE v5.0 and recorded in 
patient’s charts and CRFs.  
 
 
 
 
An adverse event (AE) is defined as any untoward medical occurrence, including an exacerbation of 
a pre-existing condition, in a patient in a clinical investigation who received a pharmaceutical product.  
The event does not necessarily have to have a causal relation with this treatment.  Grade 1 toxicities 
and lab abnormalities not deemed clinically significant will not be collected. 
 
 
7.9 
PARTICIPANT ACCESS TO STUDY AGENT AT STUDY CLOSURE 
8 
ASSESSMENT OF SAFETY 
8.1 
SPECIFICATION OF SAFETY PARAMETERS 
8.1.1 
DEFINITION OF ADVERSE EVENTS (AE) 
8.1.2 
DEFINITION OF SERIOUS ADVERSE EVENTS (SAE) 


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A serious adverse event (SAE) is defined as any AE that results in death, is immediately life-
threatening, results in persistent or significant disability/incapacity, requires or prolongs patient 
hospitalization, is a congenital anomaly/birth defect, or is to be deemed serious for any other reason 
if it is an important medical event when based on appropriate medical judgement that may jeopardize 
the patient and may require medical or surgical intervention to prevent one of the other outcomes 
listed in the above definitions. 
 
In addition, all reports of spontaneous abortion, abuse, and/or drug dependency shall be considered 
as SAEs for regulatory reporting purposes. 
 
Patients may be hospitalized for administrative or social reasons during the study (e.g., days on which 
infusion takes place, long distance from home to site). These and other hospitalizations planned at the 
beginning of the study do not need to be reported as an SAE in case they have been reported at 
screening visit in the source data and have been performed as planned. 
 
 
 
Unanticipated adverse therapy effect, any serious adverse effect on health or safety, or any life-
threatening problem or death caused by, or associated with, if that effect, problem, or death was not 
previously identified in nature, severity, or degree of incidence or any other unanticipated serious 
problem associated with the therapy that relates to the rights, safety, or welfare of subjects.   
 
 
 
 
 
 
All AEs will be graded using the CTCAE 5.0 criteria.  
For AEs not included in the protocol-defined grading system, the following guidelines will be used to 
describe severity. 
 
Mild – Events require minimal or no treatment and do not interfere with the participant’s daily activities. 
Moderate – Events result in a low level of inconvenience or concern with the therapeutic measures. 
Moderate events may cause some interference with functioning. 
Severe – Events interrupt a participant’s usual daily activity and may require systemic drug therapy 
or other treatment. Severe events are usually potentially life-threatening or incapacitating. 
 
 
 
For all collected AEs, the clinician who examines and evaluates the participant will determine the AE’s 
causality based on temporal relationship and his/her clinical judgment. The degree of certainty about 
causality will be graded using the categories below. 
 
Related – The AE is known to occur with the study agent, there is a reasonable possibility that the 
study agent caused the AE, or there is a temporal relationship between the study agent and event. 
Reasonable possibility means that there is evidence to suggest a causal relationship between the 
study agent and the AE. 
Not Related – There is not a reasonable possibility that the administration of the study agent caused 
the event, there is no temporal relationship between the study agent and event onset, or an alternate 
8.1.3 
DEFINITION OF UNANTICIPATED PROBLEMS 
8.2 
CLASSIFICATION OF AN ADVERSE EVENT 
8.2.1 
SEVERITY OF EVENT 
8.2.2 
RELATIONSHIP TO STUDY AGENT 


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etiology has been established. 
 
 
 
 
The PI will be responsible for determining whether an AE is expected or unexpected. An AE will be 
considered unexpected if the nature, severity, or frequency of the event is not consistent with the risk 
information previously described for the study agent. 
 
 
 
The study participants will be monitored closely throughout the study for occurrence of AE or SAE. 
The patients will be educated regarding most comment AEs and SAEs and will be encouraged to 
report promptly.  
 
If AEs and SAEs occur, information to be collected includes event description, time of onset, clinician’s 
assessment of severity, relationship to study product, and time of resolution/stabilization of event. All 
AEs occurring during the study will be documented appropriately, regardless of relationship. All AEs 
will be followed to adequate resolution. 
 
Any medical condition that is present at the time that the participant is screened will be considered 
as baseline and not reported as an AE. However, if the study participant’s condition deteriorates 
at any time during the study, it will be recorded as an AE. Unanticipated problems will be recorded 
in the data collection system throughout the study. 
 
Events will be followed for outcome information until resolution or stabilization is achieved. 
 
 
 
 
 
 
All AEs occurring prior to initiation of Cemiplimab-rwlc therapy do not need to be reported. 
 
All AEs occurring after first administration of Cemiplimab-rwlc therapy and 30 days after last 
administration of Cemiplimab-rwlc will be considered as on treatment. All AEs will be collected and 
graded according to CTCAE v5.0, with the exception of Grade 1 laboratory abnormalities which will 
not be collected. All Grade 2 and above toxicities will be collected and documented by the investigator, 
but only Grade 3 toxicities deemed possibly, probably or definitely related to the study treatment will 
be reported on the appropriate CRFs/SAE reporting forms. Only SAEs will be reported to the PI and 
Regeneron Pharmaceuticals, Inc. All AEs, including those persisting after end of study treatment must 
be followed up until they have resolved or have been sufficiently characterized or the principal 
investigator decides to not further pursue them. 
 
Serious and non-serious AEs occurring later than 30 days after last administration of trial drugs will 
only be reported in case they are considered drug-related or trial (procedure) related. 
 
Deaths (unless they are considered drug-related or trial related) will not be reported as SAE when 
8.2.3 
EXPECTEDNESS 
8.3 
TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-
UP 
8.4 
REPORTING PROCEDURES 
8.4.1 
ADVERSE EVENT REPORTING 


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they occur later than 30 days after last administration of the trial. 
 
Serious and non-serious AEs occurring after the subjects initiate subsequent treatment will only be 
collected if deemed related to cemiplimab-rwlc. 
 
 
 
 
All SAEs will be reported to the PI and Regeneron Pharmaceuticals, Inc. within 24 hours after 
identification and recorded in OnCore and Regeneron Pharmaceuticals, Inc. by the investigator. All 
deaths and immediately life-threatening events, whether related or unrelated to the study 
agent/procedure, will be recorded on the SAE Form and submitted to the PI and Regeneron 
Pharmaceuticals, Inc. within 24 hours of site awareness. All SAEs will be followed until satisfactory 
resolution or until the investigator deems the event to be chronic or the adherence to be stable. 
 
The reporting to Regeneron Pharmaceuticals will be done by email, medical.safety@regeneron.com. 
 
 
 
The study investigator will report to the PI unanticipated problems and it will be on the discretion of the 
PI whether to conduct an evaluation of an unanticipated problem and whether to report it to IRB.  
 
 
 
 
Not Applicable. 
 
 
 
Pregnancy when diagnosed will be reported to the PI and to the reviewing IRB as soon as possible, 
but in no event later than 10 working days after the investigator first learns of the effect.  
 
 
 
 
Administration of study agent will be halted when 3 grade 3 AEs determined to be “probably related” 
are observed.  The study sponsor and investigators will be notified immediately when the third grade 
3 event is reported and enrollment screens will stop accepting new study participants.  The Protocol 
Monitoring Committee (PMC) will convene an ad hoc meeting by teleconference or in writing as soon 
as possible. The PMC will provide recommendations for proceeding with the study to the study 
sponsor.  
 
 
 
 
Serious Adverse Events: Serious Adverse Events (SAEs) from this protocol will be reported 
concurrently to the IRB (per IRB reporting guidelines), the study sponsor via submission through The 
Online Collaborative Research Environment (OnCore). SAEs will also be reported to Regeneron 
Pharmaceuticals, Inc.  
 
8.4.2 
SERIOUS ADVERSE EVENT REPORTING 
8.4.3 
UNANTICIPATED PROBLEM REPORTING 
8.4.4 
EVENTS OF SPECIAL INTEREST 
8.4.5 
REPORTING OF PREGNANCY 
8.5 
STUDY HALTING RULES 
8.6 
SAFETY OVERSIGHT 


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Protocol Monitoring Committee (PMC): 
The PMC meets monthly and reviews accrual, patterns and frequencies of all adverse events, protocol 
violations and when applicable, internal audit results.  
 
The data and safety plan will define criteria for stopping the trial according to rules set forth by this 
protocol. This trial will be continuously monitored by the site PI and the research team at each 
participating institution. All participating sites will have a monthly teleconference calls to monitor any 
safely concerns. Safety and monitoring reports will be submitted to the PMC after completing the first 
2 cycles after the enrollment of initial 3 patients or more frequently if requested by the PMC.  No 
additional interim analyses will be conducted. A final safety and monitoring report including all 27 
patients will be submitted to the PMC within three months of completing the study enrollment. This 
protocol will be subject to periodic internal audits based on risk or as recommended by the PMC. 
 
 
 
Data will be captured in OnCore, Moffitt’s electronic Clinical Trials Database. For each participant 
enrolled, the electronic CRF must be completed by the assigned data manager or other authorized 
study staff. Any paper forms should be typed or filled out indelible ink and must be legible. Errors 
should be crossed out but not obliterated, the correction inserted, and the change initialed and dated 
by the investigator or his/her authorized delegate. This also applies to records for those patients who 
fail to complete the study. If a patient stops dosing or terminates from the study, the dates and reasons 
must be noted on the CRF. If a patient terminates from the study because of toxicity, thorough efforts 
should be made to clearly document the outcome. Regulatory documents and case report forms will 
be monitored internally according to Moffitt Cancer Center Monitoring Policies. Monitoring will be 
performed regularly by the MCC Clinical Monitoring Core for accuracy, completeness, and source 
verification of data entry, validation of appropriate informed consent process, reporting of SAEs, and 
adherence to the protocol, Good Clinical Practice (GCP) guidelines, and applicable regulatory 
requirements. The investigator should ensure the accuracy, completeness, legibility, and timeliness of 
the data reported to the Protocol Monitoring Committee. 
 
 
 
 
 
 
 
 
This is a single arm phase II clinical trial assessing the overall response rate of Cemiplimab-rwlc in 
immunocompromised patients with unresectable local recurrence and/or metastatic CSCC.   
 
 
 
We hypothesize that the response rate to Cemiplimab-rwlc in immunocompromised patients is 
clinically meaningful as observed in immunocompetent patients.  
 
 
 
The response, toxicity, and survival data obtained from immunocompromised patients treated with 
9 
CLINICAL MONITORING 
10 STATISTICAL CONSIDERATIONS 
10.1 STATISTICAL AND ANALYTICAL PLANS 
10.2 STATISTICAL HYPOTHESES 
10.3 ANALYSIS DATASETS 


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Cemiplimab-rwlc will be analyzed.   
 
 
 
 
 
 
The primary analysis of efficacy is based a one-sided exact test. 
 
 
 
The primary endpoint for efficacy analyses is the ORR. All response assessments are done by RECIST 
1.1 analysis of radiologic scans. In some patients, response assessments include photos and 
radiologic scans and evaluated by composite efficacy criteria (see Appendix 2). 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). In the case of skin 
lesions, documentation by color photography, including a ruler to estimate the size of the lesion, is 
recommended. 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 PR/CR for ORR. 
 
We expect to complete the accrual in 12 months and the total study duration will be 24 months. 
 
 
 
The secondary analyses of efficacy as measured by PFS and OS will be summarized by median 
and its 95% confidence interval using the Kaplan-Meier method. 
 
 
 
Safety observations and measurements including drug exposure, AEs, laboratory data, vital signs, 
and Eastern Cooperative Oncology Group (ECOG) performance status will be summarized and 
presented in tables and listings. 
 
 
 
A sample size of 27 achieves 83.8% power to detect a difference (P1-P0) of 0.18 using a one-sided 
exact test with a target significance level of 0.1000. The actual significance level achieved by this test 
is 0.0986. These results assume that the population proportion under the null hypothesis (P0) is 0.15. 
 
 
 
Medical and research records for this trial including but not limited to, hospital records, clinical and 
office charts, laboratory notes, will be maintained in compliance with regulatory and MCC (or 
participating) institutional requirements for the protection of confidentiality of participants. 
Investigators of the study will have access to records. 
 
10.4 DESCRIPTION OF STATISTICAL METHODS 
10.4.1 
GENERAL APPROACH 
10.4.2 ANALYSIS OF THE PRIMARY EFFICACY ENDPOINT(S) 
10.4.3 ANALYSIS OF THE SECONDARY ENDPOINT(S) 
10.4.4 
SAFETY ANALYSES 
10.5 
SAMPLE SIZE 
11 SOURCE DOCUMENTS AND ACCESS TO SOURCE 
DATA/DOCUMENTS


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Quality control procedures will be implemented beginning with the data entry system and data quality 
control checks that will be run on the database will be generated. Any missing data or data anomalies 
will be communicated for clarification/resolution. 
 
 
 
 
 
 
The investigator will ensure that this study is conducted in full conformity with Regulations for the 
Protection of Human Subjects of Research codified in 45 CFR Part 46, 21 CFR Part 50, 21 CFR 
Part 56, and/or the ICH E6. 
 
 
 
The protocol, informed consent form(s), recruitment materials, and all participant materials will be 
submitted to the IRB for review and approval. Approval of both the protocol and the consent form 
must be obtained before any participant is enrolled. Any amendment to the protocol will require 
review and approval by the IRB before the changes are implemented to the study. All changes 
to the consent form will be IRB approved; a determination will be made regarding whether 
previously consented participants need to be re-consented. 
 
 
 
 
13.3.1 
CONSENT/ASSENT AND OTHER INFORMATIONAL DOCUMENTS PROVIDED 
TO PARTICIPANTS  
 
Consent forms describing in detail the study agent, study procedures, and risks are given to the 
participant and written documentation of informed consent is required prior to initiation therapy with 
Cemiplimab-rwlc starting study product.  
 
 
 
 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in the 
study and continues throughout the individual’s study participation. Extensive discussion of risks and 
possible benefits of participation will be provided to the participants and their families. Consent forms 
will be IRB-approved, and the participant will be asked to read and review the document. The 
investigator will explain the research study to the participant and answer any questions that may arise. 
All participants will receive a verbal explanation in terms suited to their comprehension of the 
purposes, procedures, and potential risks of the study and of their rights as research participants.  
Participants will have the opportunity to carefully review the written consent form and ask questions 
prior to signing. 
12 QUALITY ASSURANCE AND QUALITY CONTROL 
13 ETHICS/PROTECTION OF HUMAN SUBJECTS 
13.1 ETHICAL STANDARD 
13.2 INSTITUTIONAL REVIEW BOARD 
13.3 INFORMED CONSENT PROCESS 
13.3.2 CONSENT PROCEDURES AND DOCUMENTATION 


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The participants would have the opportunity to discuss the study with their surrogates or think about 
it prior to agreeing to participate. The participant will sign the informed consent document prior to 
any procedures being done specifically for the study. The participants may withdraw consent at any 
time throughout the course of the trial. A copy of the informed consent document will be given to the 
participants for their records. The rights and welfare of the participants will be protected by 
emphasizing to them that the quality of their medical care will not be adversely affected if they decline 
to participate in this study. 
 
 
 
The study participant’s contact information will be securely stored at Moffitt during the study. At the 
end of the study, all records will continue to be kept in a secure location for as long a period as dictated 
by Moffitt IRB and Institutional regulations. 
 
Study participant research data, which is for purposes of statistical analysis and scientific reporting, 
will be transmitted to and stored at Moffitt. This will not include the participants’ contact or identifying 
information. Rather, individual participants and their research data will be identified by a unique study 
identification number. The study data entry and study management systems will be secured and 
password protected. At the end of the study, all study databases will be de-identified and archived at 
the Moffitt. 
 
All unpublished information that the Coordinating Center gives to the investigator shall be kept 
confidential and shall not be published or disclosed to. 
 
The contents of this protocol and any amendments and results obtained during the course of this study 
will be kept confidential by the investigator, the investigator’s staff, and the IRB/IEC and will not be 
disclosed in whole or in part to a third party without the prior written consent of the PI (or her designee).   
 
No data collected as part of this study will be utilized in any written work, including publications, without 
the written consent of the PI. All persons assisting in the performance of this study must be bound by 
the obligations of confidentiality.  
 
 
 
 
Data collected for this study will be analyzed and stored at the OnCore research database. After the 
study is completed, the de-identified, archived data will be transmitted to and stored at OnCore under 
the supervision of the PI. With the participant’s approval and as approved by local IRBs, de-identified 
biological samples will be stored at the MCC. These samples will be analyzed as proposed in the 
protocol. 
 
 
 
With the participant’s approval and as approved by local IRBs, de-identified biological samples will 
be stored at the MCC. These samples could be used for future research.  
 
During the conduct of the study, an individual participant can choose to withdraw consent to have 
biological specimens stored for future research. However, withdrawal of consent with regard to 
biosample storage will not be possible after the study is completed. 
 
13.4 PARTICIPANT AND DATA CONFIDENTIALITY 
13.4.1 
RESEARCH USE OF STORED HUMAN SAMPLES, SPECIMENS, OR DATA 
13.5 FUTURE USE OF STORED SPECIMENS 


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Data collection will be collected by investigators/clinical stuff under supervision of the PI. The 
investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness of the 
data reported. 
 
Copies of the electronic CRF (eCRF) will be provided for use as source documents and maintained 
for recording data for each participant enrolled in the study.  
 
Clinical data (including AEs and concomitant medications) and clinical laboratory data will be entered 
into Power Chart, a CFR Part 11-compliant data capture system provided by the Cerner. The data 
system includes password protection and internal quality checks, such as automatic range checks, to 
identify data that appear inconsistent, incomplete, or inaccurate. Clinical data will be entered directly 
from the source documents. 
 
 
 
 
Data will be captured in OnCore, Moffitt’s Clinical Trials Database. Regulatory documents and case 
report forms will be monitored internally according to Moffitt Cancer Center Monitoring Policies. 
Monitoring will be performed regularly to verify data is accurate, complete, and verifiable from source 
documents; and the conduct of the trial is in compliance with the currently approved 
protocol/amendments, Good Clinical Practice (GCP), and applicable regulatory requirements. 
 
To obtain access to OnCore, the External Site Coordination (ESC) office Coordinator will supply 
forms required to be completed by the site staff. Once the completed forms are received, the site 
coordinator will receive DUO access, logon/password, and information on how to access OnCore. 
The ESC office will provide OnCore training to the site once initial access is granted and on an 
ongoing basis, as needed. 
 
Following closure of the study, each participating center will maintain a copy of all site study records 
in a safe and secure location. The Coordinating Center will inform the investigator at each site at 
such time that the records may be destroyed. This will also follow each institution guidelines 
 
Study documents should be retained for a minimum of 10 years after the last approval of a marketing 
application in an International Conference on Harmonisation (ICH) region and until there are no 
pending or contemplated marketing applications in an ICH region or until at least 10 years have 
elapsed since the formal discontinuation of clinical development of the study intervention. These 
documents should be retained for a longer period, however, if required by local regulations. No 
records will be destroyed without the written consent of the sponsor, if applicable. It is the 
responsibility of the sponsor to inform the investigator when there is no longer a need for these 
documents to be retained. Permission must be acquired from the State of Florida for document 
destruction after the 10-year minimum record-retention period described above has elapsed. 
 
 
 
 
A protocol deviation is any noncompliance with the clinical trial protocol, GCP, or MOP requirements. 
14 DATA HANDLING AND RECORD KEEPING 
14.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES 
14.2 STUDY RECORDS RETENTION 
14.3 PROTOCOL DEVIATIONS 


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The noncompliance may be either on the part of the participant, the investigator, or the study site 
staff. As a result of deviations, corrective actions are to be developed by the site and implemented 
promptly. 
 
These practices are consistent with ICH E6: 
• 
4.5 Compliance with Protocol, sections 4.5.1, 4.5.2, and 4.5.3 
• 
5.1 Quality Assurance and Quality Control, section 5.1.1 
• 
5.20 Noncompliance, sections 5.20.1, and 5.20.2. 
 
It is the responsibility of the site to use continuous vigilance to identify and report deviations within 7 
working days of identification of the protocol deviation, or within 7 working days of the scheduled 
protocol-required activity. Protocol deviations must be sent to the local IRB per their guidelines. The 
site PI/study staff is responsible for knowing and adhering to their IRB requirements. Further details 
about the handling of protocol deviations will be included in the MOP. 
 
 
 
 
This study will comply with the NIH Public Access Policy, which ensures that the public has access 
to the published results of NIH funded research. It requires scientists to submit final peer-reviewed 
journal manuscripts that arise from NIH funds to the digital archive PubMed Central upon 
acceptance for publication. 
 
The International Committee of Medical Journal Editors (ICMJE) member journals have adopted a 
clinical trials registration policy as a condition for publication. The ICMJE defines a clinical trial 
as any research project that prospectively assigns human subjects to intervention or concurrent 
comparison or control groups to study the cause-and-effect relationship between a medical 
intervention and a health outcome. Medical interventions include drugs, surgical procedures, 
devices, behavioral treatments, process-of-care changes, and the like. Health outcomes include 
any biomedical or health-related 
measures obtained in patients or participants, including 
pharmacokinetic measures and adverse events. The ICMJE policy, and the Section 801 of the 
Food and Drug Administration Amendments Act of 2007, requires that all clinical trials be 
registered in a public trials registry such as ClinicalTrials.gov, which is sponsored by the National 
Library of Medicine. Other biomedical journals are considering adopting similar policies. For 
interventional clinical trials performed under NIH IC grants and cooperative agreements, it is the 
grantee’s responsibility to register the trial in an acceptable registry, so the research results may 
be considered for publication in ICMJE member journals. The ICMJE does not review specific 
studies to determine whether registration is necessary; instead, the committee recommends that 
researchers who have questions about the need to register err on the side of registration or consult 
the editorial office of the journal in which they wish to publish. 
 
FDAAA mandates that a "responsible party" (i.e., the sponsor or designated principal 
investigator) register and report results of certain "applicable clinical trials": 
 
• 
Trials of Drugs and Biologics: Controlled, clinical investigations, other than Phase I 
investigations, of a product subject to FDA regulation; 
• 
Trials of Devices: Controlled trials with health outcomes of a product subject to FDA 
14.4 PUBLICATION AND DATA SHARING POLICY 


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regulation (other than small feasibility studies) and pediatric postmarket surveillance 
studies. 
 
NIH grantees must take specific steps to ensure compliance with NIH implementation of FDAAA. 
 
It is understood that any manuscript or releases resulting from the collaborative research will be 
circulated to all participating sites prior to submission for publication or presentation. The Protocol 
Chair will be the final arbiter of the manuscript content. 
 
 
 
 
 
 
Protocol Monitoring Committee (PMC) 
 
The PMC meets monthly and reviews accrual, patterns and frequencies of all adverse events, 
protocol violations and when applicable, internal audit results. 
 
The Protocol Chair is responsible for monitoring the study. Data must be reviewed to ensure the 
validity of data, as well as the safety of the participants. The Protocol Chair will also monitor the 
progress of the trial, review safety reports, and clinical trial efficacy endpoints and to confirm that 
the safety outcomes favor continuation of the study. 
 
The Protocol Chair will be responsible for maintaining the clinical protocol, reporting adverse events, 
ensuring that consent is obtained and documented, reporting of unexpected outcomes, and 
reporting the status of the trial in the continuing renewal report submitted to the IRB and to the trial 
monitoring review group. Content of the continuing renewal report at a minimum should include year-
to-date and full trial data on the following: accrual and eligibility, protocol compliance, treatment 
administration, toxicity and ADR reports, response, survival, regulatory compliance, and compliance 
with prearranged statistical goals. The report should be submitted in a timely manner according to 
the schedule defined by the Moffitt Cancer Center Institutional Review Board. 
 
Regulatory documents and case report forms will be monitored internally according to Moffitt Cancer 
Center Monitoring Policies. Monitoring will be performed regularly by the MCC Clinical Monitoring 
Core for accuracy, completeness, and source verification of data entry, validation of appropriate 
informed consent process, reporting of SAEs, and adherence to the protocol, Good Clinical Practice 
(GCP) guidelines, and applicable regulatory requirements. 
 
 
 
 
 
 
Before the study can be initiated at any site, the site will be required to provide regulatory 
documentation to the External Site Coordination (ESC) office at Moffitt Cancer Center. Sites must 
provide a copy of their informed consent to the ESC office for review and approval prior to 
submission of any documents to the site’s IRB. Any changes requested by the site’s IRB must be 
15 STUDY ADMINISTRATION 
15.1 STUDY LEADERSHIP 
16 PARTICIPATING SITES 
16.1 REQUIRED DOCUMENTATION 


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provided to the ESC staff for review and approval prior to resubmission to the IRB. 
The ESC office must receive the following trial specific documents either by hardcopy, fax, or email 
before a site can be activated for any trial: 
1. IRB Approval Letter that includes the protocol version and date 
2. FDA Related Forms 1572/1571/310 as appropriate 
3. Signed Protocol Title Page 
4. IRB Approved Consent Form 
5. Site Delegation of Authority Log 
6. Signed Financial Interest Disclosure Forms (principal and sub investigators) 
7. Updated Investigator/Personnel documents (CVs, licenses, GCP and HSP training 
certificates, etc.) as needed 
8. Updated Laboratory Documents (certifications, normal ranges, etc.) as needed 
9. Signed protocol specific Task Order 
A study initiation teleconference will be held prior to the start of any study related activity at the site. 
Attendance is required for: 
• 
The site PI and appropriate research staff 
• 
Moffitt PI and ESC research coordinator 
The requirements of the protocol and all associated procedures and processes will be reviewed and 
agreed upon prior to the activation of the study. The ESC utilizes the EDC system, OnCore. OnCore 
training will be scheduled, if indicated, with the appropriate staff from the site.  
 
 
 
 
The following SAE reporting requirements are in addition to those detailed in section 8.4.2.  
Information about all serious adverse events will be collected and recorded. To ensure patient 
safety, each serious adverse event must be reported to the PI and to the sponsor expeditiously. 
Moffitt Cancer Center and all participating sites will report SAEs by completing an SAE report in 
OnCore, the electronic data capture system. The SAE must be reported by email 
(affiliate.research@moffitt.org) to the External Site Coordination (ESC) office within 2 working days. 
If applicable, the site should also follow protocol guidelines for additional reporting to government 
agencies. 
 
 
 
All subjects must be registered with the External Site Coordination (ESC) office to be able to 
participate in a trial. The participating site must fax or email the completed study specific eligibility 
checklist and registration forms, supporting documents and signed informed consent to the 
Coordinating Center. Unsigned or incomplete forms will be returned to the site. Once documents 
are received, the ESC Research Coordinator will review them to confirm eligibility and to complete 
the registration process. If eligibility cannot be confirmed, the research coordinator will query the site 
for clarification or additional documents as needed. Subjects failing to meet all study eligibility 
requirements will not be registered and will be unable to participate in the trial.  
Upon completion of registration, the ESC Research Coordinator will provide the participating site 
with the study sequence number and randomization information, if indicated. Within 24-48 hours 
after registration, it is the site’s responsibility to:  
• 
Enter the demographic and on-study patient information into the Oncore database 
• 
Order investigational agent(s) if indicated per protocol 
 
16.2 SAE REPORTING 
16.3 REGISTRATION PROCEDURES 


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It is the responsibility of the participating Investigator or designee to inform the subject of the 
research treatment plan and to conduct the study in compliance with the protocol as agreed upon 
with Moffitt Cancer Center and approved by the site’s IRB.  
To register a patient send the completed signed eligibility checklist along with the patient registration 
form and supporting documentation to the ESC via email at affiliate.research@moffitt.org or via fax 
at 813-745-5666, Monday through Friday between 8:00AM and 5:00PM (EST). 
 
 
 
The independence of this study from any actual or perceived influence, such as by the 
pharmaceutical industry, is critical. Therefore, any actual conflict of interest of persons who have 
a role in the design, conduct, analysis, publication, or any aspect of this trial will be disclosed and 
managed. Furthermore, persons who have a perceived conflict of interest will be required to have 
such conflicts managed in a way that is appropriate to their participation in the trial.  The study 
leadership in conjunction with the study sponsor has established policies and procedures for all 
study group members to disclose all conflicts of interest and will establish a mechanism for the 
management of all reported dualities of interest. 
 
 
 
 
 
 
 
 
1. 
Nehal KS, Bichakjian CK: Update on Keratinocyte Carcinomas. N Engl J Med 379:363-374, 
2018 
 
2. 
Wei-Passanese EX, Han J, Lin W, et al: Geographical variation in residence and risk of multiple 
nonmelanoma skin cancers in US women and men. Photochem Photobiol 88:483-9, 2012 
 
3. 
Xiang F, Lucas R, Hales S, et al: Incidence of nonmelanoma skin cancer in relation to ambient 
UV radiation in white populations, 1978-2012: empirical relationships. JAMA Dermatol 150:1063-71, 2014 
 
4. 
Migden MR, Rischin D, Schmults CD, et al: PD-1 Blockade with Cemiplimab in Advanced 
Cutaneous Squamous-Cell Carcinoma. N Engl J Med 379:341-351, 2018 
 
5. 
Kauvar AN, Arpey CJ, Hruza G, et al: Consensus for Nonmelanoma Skin Cancer Treatment, 
Part II: Squamous Cell Carcinoma, Including a Cost Analysis of Treatment Methods. Dermatol Surg 41:1214-
40, 2015 
 
6. 
Manyam BV, Garsa AA, Chin RI, et al: A multi-institutional comparison of outcomes of 
immunosuppressed and immunocompetent patients treated with surgery and radiation therapy for 
cutaneous squamous cell carcinoma of the head and neck. Cancer 123:2054-2060, 2017 
 
7. 
Tomaszewski JM, Gavriel H, Link E, et al: Aggressive behavior of cutaneous squamous cell 
carcinoma in patients with chronic lymphocytic leukemia. Laryngoscope 124:2043-8, 2014 
 
8. 
Porceddu SV, Veness MJ, Guminski A: Nonmelanoma Cutaneous Head and Neck Cancer and 
Merkel Cell Carcinoma: Current Concepts, Advances, and Controversies. J Clin Oncol 33:3338-45, 2015 
 
9. 
Strome SE, Dong H, Tamura H, et al: B7-H1 blockade augments adoptive T-cell 
immunotherapy for squamous cell carcinoma. Cancer Res 63:6501-5, 2003 
 
10. 
Topalian SL, Hodi FS, Brahmer JR, et al: Safety, activity, and immune correlates of anti-PD-1 
antibody in cancer. N Engl J Med 366:2443-54, 2012 
17 CONFLICT OF INTEREST POLICY 
18 LITERATURE REFERENCES 


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11. 
Bari S, Muzaffar J, Chan A, et al: Outcomes of Programmed Cell Death Protein 1 (PD-1) and 
Programmed Death-Ligand 1(PD-L1) Inhibitor Therapy in HIV Patients with Advanced Cancer. J Oncol 
2019:2989048, 2019 
 
12. 
Cook MR, Kim C: Safety and Efficacy of Immune Checkpoint Inhibitor Therapy in Patients With 
HIV Infection and Advanced-Stage Cancer: A Systematic Review. JAMA Oncol 5:1049-1054, 2019 
 
13. 
LIBTAYO (cemiplimab-rwlc) injection, for intravenous use. Package Insert, 2018 
 
14. 
Rizvi NA, Hellmann MD, Snyder A, et al: Cancer immunology. Mutational landscape 
determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 348:124-8, 2015 
 
15. 
Gandara DR, Paul SM, Kowanetz M, et al: Blood-based tumor mutational burden as a 
predictor of clinical benefit in non-small-cell lung cancer patients treated with atezolizumab. Nat Med, 2018 
 
16. 
Chung CH, Frampton GM, Chalmers ZR, et al: Genomic Profiling of Squamous Malignancies 
Across Anatomic Sites. J Clin Oncol 35:abstr 11512, 2017 
 
17. 
Bettegowda C, Sausen M, Leary RJ, et al: Detection of circulating tumor DNA in early- and 
late-stage human malignancies. Sci Transl Med 6:224ra24, 2014 
 
 
 
 
 


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APPENDIX 1: MANAGEMENT ALGORITHMS 
 
These general guidelines constitute guidance to the Investigator and may be supplemented at the 
discretion of the treating physician. The guidance applies to all immuno-oncology agents and 
regimens. 
 
A general principle is that differential diagnoses should be diligently evaluated according to standard 
medical practice. Non-inflammatory etiologies should be considered and appropriately treated. 
 
Corticosteroids are a primary therapy for immuno-oncology drug-related adverse events. The oral 
equivalent of the recommended IV doses may be considered for ambulatory patients with low-grade 
toxicity. The lower bioavailability of oral corticosteroids should be taken into account when switching 
to the equivalent dose of oral corticosteroids. 
 
Consultation with a medical or surgical specialist, especially prior to an invasive diagnostic or 
therapeutic procedure, is recommended. 
 
The frequency and severity of the related adverse events covered by these algorithms will depend on 
the immuno-oncology agent or regimen being used. 
 
Patients will not be able to resume treatment following events that require Cemiplimab-rwlc to be 
discontinued for more than 84 days (12 weeks) from last scheduled dose. Reference the Dose 
Adjustments/Modifications/Delays section for additional details. 
 
 
APPENDIX 


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Events 
CTCA
E v5 
Grade 
Management
/Cemiplimab 
Dosing 
Action/Supportive Care Guidelines 
Colitis events 
• Bowel 
obstruction 
• Colitis 
• Colitis 
microscopic 
• Enterocolitis 
hemorrhagic 
• GI perforation 
• Necrotizing 
colitis 
• Diarrhea:  
All patients who 
experience 
diarrhea should 
be advised to 
drink liberal 
quantities of clear 
fluids. If sufficient 
oral fluid intake is 
not feasible, fluid 
and electrolytes 
should be 
substituted via IV 
infusion. 
≤Grad
e 1 
No change in 
dose 
• For diarrhea, treat symptomatically (loperamide, oral 
hydration, electrolyte substitution and ADA colitis diet). 
Endoscopy is recommended if symptoms persist. 
• Grade 1 diarrhea that persist for >1 week should be treated 
with the addition of oral diphenoxylate hydrochloride and 
atropine sulfate four times daily and budesonide 9 mg daily. 
Grade 
2 
Hold until 
<Grade 1. 
Resume at 
same dose. 
• GI consultation and endoscopy is recommended to confirm 
or rule out colitis for grade 2 diarrhea that persists >1 week 
or grade 1-2 diarrhea with rectal bleeding (additional 
guidelines for the treatment of persistent colitis are provided 
below). 
• Grade 2 diarrhea should be treated with the addition of oral 
diphenoxylate hydrochloride and atropine sulfate four times 
daily and budesonide 9 mg daily. 
• Grade 2 diarrhea with diffuse ulceration and bleeding seen 
on endoscopy may require oral steroids with prolonged 
taper and represent an increased risk for the development 
of bowel perforation. Consider prophylactic antibiotics for 
opportunistic infections. 
• When symptoms improve to Grade 1 or less, steroid taper 
should be started and continued over no less than 4 weeks. 
• In patients with Grade 2 enterocolitis, cemiplimab should be 
withheld and antidiarrheal treatment should be started. If 
symptoms are persistent for more than one week, systemic 
corticosteroids should be initiated (eg, 0.5 mg/kg/day of 
prednisone or equivalent). When symptoms improve to 
Grade 1 or less, corticosteroid taper should be started and 
continued over at least 1 month. 
Grade 
3-4 
Hold 
cemiplimab 
Discontinue 
if unable to 
reduce 
corticosteroid 
dose to ≤ 10 
mg per day 
prednisone 
equivalent 
within 12 
weeks of 
toxicity 
• In patients with Grade 3 enterocolitis, cemiplimab will be 
permanently discontinued and treatment with systemic 
corticosteroids should be initiated at a dose of 1–2 
mg/kg/day of prednisone or equivalent. When symptoms 
improve to Grade 1 or less, corticosteroid taper should be 
started and continued over at least 1 month. Consider 
prophylactic antibiotics for opportunistic infections. 
For Grade 3–4 diarrhea (or Grade 2 diarrhea that persists 
after initial steroid treatment), 
• Rule out bowel perforation. Imaging with plain films or 
computed tomography (CT) can be useful.  
• Consider consultation with gastroenterologist and 
confirmation biopsy with endoscopy. 
• Treat with intravenous (IV) steroids (methylprednisolone 125 
mg) followed by high-dose oral steroids (prednisone 1–2 
mg/kg once per day or dexamethasone 4 mg every 4 hours). 
When symptoms improve to Grade 1 or less, steroid taper 
should be started and continued over no less than 4 weeks. 
Taper over 6–8 weeks in patients with diffuse and severe 
ulceration and/or bleeding. 


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• If IV steroids followed by high dose oral steroids does not 
reduce initial symptoms within 48–72 hours, consider 
treatment with infliximab at 5 mg/kg once every 2 weeks. 
Discontinue infliximab upon symptom relief and initiate a 
prolonged steroid taper over 45–60 days. If symptoms 
worsen during steroid reduction, initiate a retapering of 
steroids starting at a higher dose of 80 or 100 mg followed 
by a more prolonged taper and administer infliximab. 
CAUTION: infliximab is contraindicated in patients with 
bowel perforation or sepsis. 
• If symptoms persist despite the above treatment a surgical 
consult should be obtained.  
Endocrine 
events 
• Hyperthyroidism 
• Hypopituitarism 
Grade 
1-2 
No change in 
dose 
• Monitor thyroid function or other hormonal level tests and 
serum chemistries more frequently until returned to baseline 
values. 
Endocrine 
events 
• Hypothyroidism 
• Thyroid disorder 
• Thyroiditis 
Grade 
3-4 
Hold until on 
stable 
replacement 
dose 
• Consider endocrine consultation.  
• Rule out infection and sepsis with appropriate cultures and 
imaging.  
• Replacement of appropriate hormones as required. 
Endocrine 
events 
• Adrenal 
insufficiency 
• Hypophysitis 
• Pan-
hypopituitarism 
Grade 
1-4 
Hold until on 
stable 
replacement 
dose 
• Thyroid hormone and/or steroid replacement therapy to 
manage adrenal insufficiency.  
• If Grade 1-2 hypophysitis is considered, pituitary gland 
imaging should be considered (magnetic resonance imaging 
[MRIs] with gadolinium and selective cuts of the pituitary can 
show enlargement or heterogeneity and confirm the 
diagnosis).  
• Grade 3-4 hypophysitis with clinically significant adrenal 
insufficiency and hypotension, dehydration, and electrolyte 
abnormalities (such as hyponatremia and hyperkalemia) 
constitutes adrenal crisis. Hospitalization and IV 
methylprednisolone should be initiated. 
Eye event: 
Uveitis   
(iritis, iridocyclitis) 
Grade 
1 
Discontinue 
cemiplimab if 
symptoms 
persist 
despite 
treatment 
with topical 
immunosupp
ressive 
therapy   
• Evaluation by an ophthalmologist is strongly recommended. 
•  Treat with topical steroids such as 1% prednisolone acetate 
suspension and iridocyclitics. 
Grade 
2 
Discontinue 
cemiplimab if 
symptoms 
persist 
despite 
treatment 
with topical 
immunosupp
ressive 
• Evaluation by an ophthalmologist is strongly recommended.  
• Treat with topical steroids such as 1% prednisolone acetate 
suspension and iridocyclitics. 
• Discuss with and obtain approval from site PI prior to 
resumption once there is resolution to grade ≤1 


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therapy and 
do not 
improve to 
Grade 1 
within the 
retreatment 
period OR 
requires 
systemic 
treatment.  
Grade 
3-4 
Discontinue 
cemiplimab.  
• Treat with systemic corticosteroids such as prednisone at a 
dose of 1-2 mg/kg per day. When symptoms improve to 
≤Grade 1, steroid taper should be started and continued 
over no less than 4 weeks. 
• Discuss with and obtain approval from site PI prior to 
resumption once there is resolution to grade ≤1 
Hepatic events 
• Hepatitis 
• Hepatitis, 
Autoimmune 
Grade 
1-2 
Withhold 
cemiplimab if 
there is a 
treatment-
emergent 
concurrent 
elevation of 
ALT and 
bilirubin that 
corresponds 
to an upward 
shift of 2 or 
more grades 
in both 
parameters. 
• Monitor liver function tests more frequently until returned to 
baseline values. 
Grade 
3-4 
Withhold 
(and 
consider 
Discontinuati
on of) 
cemiplimab 
when AST or 
ALT  
>5.0 times 
ULN and/or 
total bilirubin 
>3.0 times 
ULN. 
• Consider appropriate consultation and liver biopsy to 
establish etiology of hepatic injury, if necessary.  
• Treat with high-dose IV glucocorticosteroids for 24–48 
hours. When symptoms improve to grade 1 or less, a steroid 
taper with dexamethasone 4 mg every 4 hours or 
prednisone at 1–2 mg/kg should be started and continued 
over no less than 4 weeks. 
• If serum transaminase levels do not decrease 48 hours after 
initiation of systemic steroids, oral mycophenolate mofetil 
500 mg every 12 hours may be given. Infliximab is not 
recommended due to its potential for hepatotoxicity.  
• Several courses of steroid tapering may be necessary as 
symptoms may worsen when the steroid dose is decreased. 
Pneumonitis 
events 
• Pneumonitis 
• Interstitial lung 
disease 
• Acute interstitial 
pneumonitis 
Grade 
1 
Consider 
hold of 
therapy. 
Cemiplimab 
may be 
continued 
with close 
monitoring. 
• 
Radiologic findings should be followed on serial 
imaging studies at least every 3 weeks.  
• 
Monitor for symptoms every 2–3 days.  
• 
Consider pulmonary consultation and/or bronchoscopy 
if clinically indicated. 


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Grade 
2 
Hold 
Cemiplimab 
To rule out other causes such as infection: 
• Consider pulmonary consultation with bronchoscopy and 
biopsy/bronchoalveolar lavage (BAL). 
• Consider pulmonary function test. 
• Follow radiologic findings on serial imaging studies every 1-
3 days. 
If the patient is determined to have study drug associated 
pneumonitis:  
• Monitor symptoms daily; consider hospitalization. 
• Treat with systemic corticosteroids at a dose of 1-2 
mg/kg/day prednisone or equivalent. When symptoms 
improve to Grade 1 or less, steroid taper should be started 
and continued over no less than 4 weeks. 
• Treatment with cemiplimab may be resumed if the event 
improves to ≤ Grade 1 within 12 weeks and corticosteroids 
have been reduced to the equivalent of methylprednisolone 
10 mg by mouth daily or less. Repeat chest imaging monthly 
as clinically indicated.  
For Grade 2 pneumonitis that improves to ≤Grade 1 within 12 
weeks, the following rules should apply:  
• First episode of pneumonitis: May increase dosing interval 
by one week in subsequent cycles. 
• Second episode of pneumonitis: Discontinue cemiplimab if 
upon rechallenge the patient develops a second episode of 
≥ Grade 2 pneumonitis. 
Grade 
3-4 
Discontinue 
cemiplimab 
• Consider pulmonary function tests with pulmonary consult. 
• Bronchoscopy with biopsy and/or BAL is recommended. 
• Treat with IV steroids (2–4 mg/kg per day prednisone or 
equivalent). When symptoms improve to grade 1 or less, a 
high-dose oral steroid (1–2 mg/kg prednisone once per day 
or 4 mg dexamethasone every 4 hours) taper should be 
started and continued over no less than 4 weeks.  
• Add prophylactic antibiotics for opportunistic infections.  
• If IV steroids followed by high-dose oral steroids does not 
reduce initial symptoms within 48–72 hours, treat with 
infliximab at 5 mg/kg once every 2 weeks. Discontinue 
infliximab upon symptom relief and initiate a prolonged 
steroid taper over 45–60 days. If symptoms worsen during 
steroid reduction, initiate a retapering of steroids starting at a 
higher dose of 80 or 100 mg followed by a more prolonged 
taper and administer infliximab. 
Renal events 
• Nephritis 
• Nephritis 
autoimmune 
• Renal failure 
Grade 
1 
Consider 
withholding 
Cemiplimab 
if event does 
not improve 
with 
• Provide symptomatic treatment. 
• Monitor creatinine weekly; when it returns to baseline, 
resume routine creatinine monitoring per protocol. 


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• Renal failure, 
Acute 
symptomatic 
treatment.  
 
Grade 
2 
Consider 
withholding 
Cemiplimab. 
• Systemic corticosteroids at a dose of 1–2 mg/kg/day of 
prednisone or equivalent may be indicated. When symptoms 
improve to Grade 1 or less, corticosteroid taper should be 
started and continued over at least 1 month.  
• Consider prophylactic antibiotics for opportunistic infections. 
• Consider renal biopsy. 
• If elevations persist >7 days or worsen, treatment as Grade 
4. 
Grade 
3-4 
Discontinue 
cemiplimab  
• Renal consultation with consideration of ultrasound and/or 
biopsy as appropriate.  
• Monitor creatinine daily. 
• Treat with systemic corticosteroids at a dose of 1–2 mg/kg 
prednisone or equivalent once per day. 
• When symptoms improve to grade 1 or less, steroid taper 
should be started and continued over no less than 4 weeks. 
• Discontinue cemiplimab if unable to reduce corticosteroid 
dose for irAEs to ≤10 mg. 
• Cemiplimab treatment may be restarted if symptoms 
resolve. 
Skin events 
• Dermatitis 
exfoliative 
• Erythema 
multiforme 
• Stevens-
Johnson 
syndrome 
• Toxic epidermal 
necrolysis 
If considered to 
be immune 
related,  
≥ Grade 3 or 
result in dose 
modification or 
discontinuation: 
• Pruritus 
• Rash 
• Rash, 
generalized 
• Rash 
maculopapular 
• Vitiligo 
Grade 
1-2 
No change 
• 
Symptomatic treatment should be given such as 
topical glucocorticosteroids (eg, betamethasone 0.1% cream 
or hydrocortisone 1%) or urea-containing creams in 
combination with oral antipruritics (eg, diphenhydramine HCl 
or hydroxyzine HCl).  
• 
Treatment with oral steroids is at investigator discretion 
for Grade 2 events. 
Grade 
3 
Hold 
cemiplimab 
• 
Consider dermatology consultation and biopsy for 
confirmation of diagnosis.  
• 
Treatment with oral steroids is recommended, starting 
with 1 mg/kg prednisone or equivalent once per day or 
dexamethasone 4 mg four times orally daily. When 
symptoms improve to Grade 1 or less, steroid taper should 
be started and continued over no less than 4 weeks. 
Grade 
4 
Permanently 
discontinue 
cemiplimab 
• 
Dermatology consultation and consideration of biopsy 
and clinical dermatology photograph.  
• 
Initiate steroids at 1–2 mg/kg prednisones or 
equivalent. When symptoms improve to grade 1 or less, 
steroid taper should be started and continued over no less 
than 4 weeks. 
 
  
 
 


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APPENDIX 2: COMPOSITE RESPONSE CRITERIA FOR PATIENTS WITH LOCALLY ADVANCED 
CSCC 
 
These criteria are designed primarily for patients whose target lesions will be evaluated by 
clinical measurements (ie caliper or ruler measurements).  This appendix also provides composite 
response criteria for disease that is measurable by both clinical response criteria and radiographic 
images.  These patients will be followed by clinical measurements and will also undergo 
radiologic imaging at baseline, and this will also be performed serially at each response assessment 
unless the investigator deems that baseline radiologic imaging was uninformative.  Radiologic 
imaging will be essential in the evaluation of tumors that have subdermal components that cannot be 
adequately assessed by clinical measurements. 
 
A new cutaneous lesion consistent with CSCC will be considered as PD if the lesion is ≥10 mm in 
both maximal perpendicular diameters, and can be clearly documented as not being previously 
present, unless it is confirmed on biopsy not to be consistent with CSCC. If a new cutaneous lesion 
is not biopsied or if the histology is inconclusive, it should be considered CSCC and deemed PD. 
 
Composite Response Criteria 
These criteria are for patients who have locally advanced or metastatic CSCC that is measurable by 
BOTH clinical response criteria by clinical measurement and radiologic imaging.   
 
Clinical Response  
(caliper/ ruler) 
Radiographic 
Response (CT/MRI) 
Composite 
(Overall) Response 
CR 
CR or NAa 
CR 
NAa 
CR 
CR 
CR 
PR or SD 
PR 
PR 
CR, PR, SD or NAa 
PR 
NA 
PR 
PR 
SD 
CR or PR 
PR 
SD 
SD or NAa 
SD 
NAa 
SD 
SD 
PD 
Any 
PD 
Any 
PD 
PD 
a NA indicates “Not applicable” (eg, because the assessment was not done) 
 
In addition, if all previously inoperable target lesions are rendered operable with clear margins 
obtained at the time of surgery, this will be considered a PR. 

ICF_001.pdf: 
A Single Arm Phase II Study of  
Cemiplimab-rwlc in Immunocompromised 
Patients with Unresectable Locally Recurrent 
and/or Metastatic Cutaneous Squamous Cell 
Carcinoma (CSCC) 
 
NCT04242173 
 
ICF Version 3 Dated 7/23/2020 


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CONSENT TO TAKE PART IN A CLINICAL RESEARCH STUDY 
AND 
AUTHORIZATION TO DISCLOSE HEALTH INFORMATION 
 
 
 
Study 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) 
 
Protocol Number: 
 
Sponsor: 
MCC 20114 
 
Moffitt Cancer Center 
 
Principal Investigator: 
(Study Doctor) 
 
Christine H. Chung, MD 
 
Telephone: 
(24 hour number) 
813-745-5061 
800-456-3434 
Address: 
Moffitt Cancer Center 
12902 Magnolia Drive 
Tampa, FL    33612 
 
Moffitt Cancer Center McKinley  
10920 N. McKinley 
Tampa, FL    33612 
 
 
You are being asked to take part in a research study.  The information in this document should 
help you to decide if you would like to participate. 
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).  About 27 
participants will participate in this study. 
During the study, you will receive Cemiplimab study treatment that will be administered every 21 
days for approximately 1 year (17 cycles).  Each study treatment will be administered 
intravenously for approximately 30 minutes.  You will stop receiving study treatment prior to 1 
year if your disease progresses, you experience intolerable side effects, or you withdraw your 
consent for study participation.   
Some of the most common side effects of Cemiplimab include fatigue, nausea, diarrhea, 
constipation, decreased appetite, and rashes. Cemiplimab can also cause side effects called 
immune-related adverse reactions.  These side effects can be serious and require corticosteroid 
treatment or discontinuation of the study medication. Some examples of these immune-related 


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side-effects are pneumonitis (inflammation of the lung), colitis (inflammation of the colon), and 
hepatitis (inflammation of the liver).  Please see the “ARE THERE RISKS TO ME IF I AM IN 
THIS STUDY” section of this form for additional immune-related side effects.  Other potential 
serious side effects include, but are not limited to, diabetic ketoacidosis (a potentially dangerous 
buildup of acids in your blood), damage to the liver, infusion related reactions, and Guillain-
Barre Syndrome (damage to the nervous system).  Please review the “ARE THERE RISKS TO 
ME IF I AM IN THIS STUDY?” section of this form for additional information on Cemiplimab side 
effects.  
In addition to receiving the study drug, throughout the study you will visit the clinic and undergo 
the following procedures:  you will be asked questions about your medical history and any 
medications you are currently taking; you will be asked questions about any symptoms you may 
be experiencing; you will complete physical exams and your vital signs will be assessed; you 
will complete laboratory tests; you will complete a pregnancy test, if applicable; you will undergo 
imaging studies (CT/MRI); and you may provide an optional tumor biopsy.  Additional 
information about the study procedures can be found in the “WHAT WILL HAPPEN DURING 
THIS STUDY?” section of this form.  
Your participation is voluntary, and you may stop your participation at any time.  There will be no 
penalties or loss of benefits or opportunities if you do not participate or decide to stop once you 
start.  Any new important information that is discovered during the study which may influence 
your willingness to continue participation will be provided to you. 
We do not know if you will receive any benefit from your participation.  There is no cost to 
participate.  You will not be compensated for your participation.   
Even if we publish the findings from this study, we will keep your study information private and 
confidential.  Anyone with the authority to look at your records must keep them confidential. 
 
WHAT IS THIS STUDY ABOUT? 
You are being asked to participate in this research study because you have a weakened 
immune system and unresectable (cannot be removed by surgery) locally recurrent and/or 
metastatic cutaneous squamous cell carcinoma (CSCC).  
The purpose of this research study is to: 
• 
test the safety and effectiveness of the study drug, Cemiplimab.    
This research study will test the investigational drug, Cemiplimab.  Cemiplimab is approved by 
the United States Food and Drug Administration (FDA) for the treatment of patients with 
metastatic cutaneous squamous cell carcinoma (CSCC) or locally advanced CSCC who are not 
candidates for curative surgery or curative radiation.  This study is designed to test the safety of 
Cemiplimab and to see how your type of cancer responds to Cemiplimab study treatment in 
participants with weakened immune systems. 
 


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WHAT WILL HAPPEN DURING THIS STUDY? 
Screening: 
Before any study-related tests and procedures are performed, you will be asked to read, sign 
and date this consent document.  The following screening tests and procedures will then be 
performed to determine if you qualify to take part in this study: 
• 
You will be asked questions about your medical history 
• 
You will be asked questions regarding any symptoms you may be having  
• 
You will be asked questions about your daily activities  
• 
Your vital signs will be taken 
• 
You will complete a physical exam 
• 
Blood will be collected for laboratory tests 
• 
You will complete a pregnancy test, if applicable 
• 
You will complete a computed tomography (CT)/magnetic resonance imaging (MRI) 
scan of the head/neck/chest/abdomen/pelvis and other areas where your cancer is. You 
may also have photographs taken of your cancer, if visible. 
• 
You will provide an archived tumor sample (tissue from a previous biopsy or surgery) 
• 
You will be asked to provide an optional, new tumor biopsy sample 
• 
You will be asked about any medications you may be taking 
• 
You will provide demographic information (such as age, gender, etc.) 
If you qualify to take part in this study and go on to receive the study treatment then the 
following will happen: 
Study Treatment:  
You will receive Cemiplimab every 21 days for approximately 1 year (17 cycles).  Each study 
treatment will be administered intravenously (directly into your vein) for approximately 30 
minutes.  You will stop receiving study treatment prior to 1 year if your disease progresses, you 
experience intolerable side effects or you withdraw your consent for study participation.  
Because this is a research study, the study drug will be given to you only during this study and 
not after the study is over. 
During the study treatment portion of the study, you will continue to come to the clinic for study 
visits and undergo the following procedures: 
• 
You will complete physical exams 
• 
Your vital signs will be taken 
• 
Blood will be collected for laboratory tests 
• 
You will complete CTs/MRIs of the head/neck/chest/abdomen/pelvis and other areas 
where your cancer is. You may also have photographs taken of your cancer, if visible.  
• 
You will be asked about any medications you are taking 
• 
You will be asked about any symptoms you may be experiencing 
End of Study Treatment Visit: 
An end of study treatment visit will be performed once you end the study treatment period for 
any reason (your disease progresses, you have harmful side effects, or if you with withdraw 
your consent to participate in the study).  This visit will take place approximately 30 days after 
your last dose of Cemiplimab.  During this visit, the following procedures will be performed: 


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• 
You will complete a physical exam 
• 
Your vital signs will be taken 
• 
Blood will be collected for laboratory tests 
• 
You will be asked about any medications you may be taking 
• 
You will be asked about any symptoms you may be experiencing 
• 
You will be asked to provide an optional, new tumor biopsy sample 
• 
You will complete a CT/MRI of the head/neck/chest/abdomen/pelvis and other areas 
where your cancer is. You may also have photographs taken of your cancer, if visible.  If 
you have had these procedures performed recently, it may not be necessary to repeat. 
Final Study Visit: 
At the end of the study (about 24 months after your first dose of Cemiplimab) you will complete 
a final study visit.  During this visit, the following procedures will be performed: 
• 
Blood will be collected for research purposes 
Follow-Up Study Visits: 
You will return to the study clinic approximately 6 months and 12 months after your end of 
treatment visit for a physical exam and laboratory tests 
Additional information on the required study procedures can be found below: 
• 
Demographic Questions:  you will be asked to give personal information, such as your 
name, date of birth, and race. 
• 
Health and Medication Questions: you will be asked to answer questions about your 
health, your medical history, and the medications you take. 
• 
Physical Exam:  a comprehensive physical exam, including a neurological evaluation, 
will be performed.  You should ask you study doctor to explain what will happen during 
this exam. 
• 
Vital Signs:  the study team will check your blood pressure by putting a band around 
your arm (this will squeeze your arm for about a minute), check your pulse, listen to you 
breathe in and out, and will take your temperature.  Your height and weight will also be 
assessed. 
• 
Blood Testing:  blood will be collected for laboratory tests 
o Some of your blood will be used to check on your health. 
o Some of your blood will be used for research purposes. 
• 
Pregnancy Testing:  a blood or urine test will be performed to see if you are pregnant.  
You will only have pregnancy testing if you are a woman and can have children.  The 
study doctor or study staff will tell you if the pregnancy test results are positive.  The 
results of the pregnancy testing must be negative in order for you to be in the study. 
• 
CT Scan:  A CT scan uses radiation (x-rays) to make pictures of the inside of your body.  
The scan can show a cross-section (a thin “slice”) of your body, or can show the body 
tissues and structure in 3 dimensions (“3-D”).  The study doctor or study staff may give 
you a contrast dye, either by mouth or with a needle.  The study doctor can tell you more 
about contrast dye. 
• 
MRI:  An MRI uses powerful magnets and radio waves to make pictures of body tissues 
and structure.  


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• 
Optional Biopsies: If you agree, a tissue sample will be collected, prior to receiving the 
study drug (during the screening portion of the study) and at the end of the study. The 
information obtained from these samples will be used for future research of your 
disease.  You do not have to provide the samples in order to participate in this study.  
You will be asked to provide your consent to the optional biopsies at the end of this 
consent form.   
 
HOW WILL MY SAMPLES BE USED? 
In addition to the procedures outlined above, we are asking you to allow us to store your 
optional tumor biopsies and blood samples, collectively referred to as “tissue”, for use in 
future research.  These samples may be used for research on your disease or condition and 
others to assist in the development of new treatments. 
In addition to your samples being used for this study and future research, we would like to 
share them with other researchers.  We will code your samples so that the researcher who 
uses it for other purposes does not know your identity.  We will not release the code that 
links your sample to your personal identifying information for any reason. 
This study also involves genetic testing.  Genes control how your body grows and changes, and 
how your body reacts to certain things.  Genes are what we get from our parents that help make 
our bodies what they are.  For example, eye and hair color depend on the genes we received 
from our parents.  We want to find out how genes work in skin cancer.  It may be true that some 
people are more likely to have skin cancer because of their genes and we would like to learn 
more about this. 
As part of this study, a blood sample will be obtained and DNA from your blood sample will be 
purified.  DNA, or deoxyribonucleic acid, stores and transmits inherited traits, such as eye color 
or blood type.  As part of this research project, your DNA will be studied in an effort to find out if 
there are genes that contribute to medical conditions that are part of this study. 
We will not tell you what we find out about your genes.  For example, we might find out that you 
have a certain kind of gene.  We may know that if people have this gene, they sometimes get a 
certain disease or do not respond to treatment.  You could have a gene that makes it more likely 
that you will have a health problem.  However, that does not mean you will get that health 
problem.  You should ask the study team or a genetic counselor if you have any questions 
about genetic research. 
Your sample will be stored with your name or other identifying information and health 
information linked to it.  We will not share your name or other information that identifies you 
unless it is required by law.  Since your genetic sample is linked to identifying information, 
should you choose to withdraw your consent to use the sample at a later date, please contact 
the study team.  The study team will remove your sample from the research and immediately 
destroy it so that it can no longer be used.  Please understand that part of your sample may 
have been used prior to the withdrawal of your consent. 
Researchers can look closely at large amounts of your genetic information by sequencing, or 
“reading”, every letter in your DNA (your genome).  Reading a person’s entire genetic code is 
called whole genome sequencing.  The research will include whole genome sequencing (i.e., 


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sequencing of a human germline or somatic specimen with the intent to generate the genome or 
exome sequence of that specimen). 
As part of the genetic study, a sample of your DNA may have Genome Wide Association 
Studies (GWAS) performed.  This analysis creates a very detailed picture of your DNA for 
researchers.  In addition, information regarding your DNA and clinical information about you will 
be sent to the National Institute for Health’s Genome Wide Association Study (GWAS) data 
repository, where it will undergo genome-wide analysis and be shared with other investigators 
for research purposes.  DNA and information sent to the GWAS database will help researchers 
better understand how genes affect the risk of developing diseases and may lead to better 
methods to select the best treatment options.  Before your information is sent to the GWAS data 
repository it will be de-identified, which means that we will remove any identifying information 
such as your name, date of birth, address, etc.  Thus, researchers using your DNA and clinical 
data will not be able to link this information back to you. 
Genetic Information Nondiscrimination Act (GINA) 
A Federal law, called the Genetic Information Nondiscrimination Act (GINA), generally makes it 
illegal for health insurance companies, group health plans, and most employers to discriminate 
against you based on your genetic information.  This law generally will protect you in the 
following ways: 
• 
Health insurance companies and group health plans may not request your genetic 
information that we get from this research. 
• 
Health insurance companies and group health plans may not use your genetic 
information when making decisions regarding your eligibility or premiums. 
• 
Employers with 15 or more employees may not use your genetic information that we get 
from this research when making a decision to hire, promote, or fire you or when setting 
the terms of your employment. 
All health insurance companies, group health plans, and employers as outlined above must 
follow this law.  Please note that this new Federal law does not protect you against genetic 
discrimination by companies that sell life insurance, disability insurance, or long-term care 
insurance. 
 
WHO IS PAYING FOR THIS STUDY? 
A company called Regeneron Pharmaceuticals, Inc., the manufacturer of the study drug, is 
paying for this study. 
 
WILL IT COST ANYTHING TO BE IN THIS STUDY? 
You and/or your insurance company will be financially responsible for hospital inpatient, 
outpatient and follow-up visits that would normally or routinely occur in the management of your 
disease.  Inpatient and outpatient visits could include charges for treatments, medications, 
physician visits, laboratory tests and procedures.   You and /or your insurance company will be 
responsible for paying for the charges which are considered routine, since you would have 
received these services even if you were not participating in this study.   You will be responsible 
for any costs not covered by your insurance company, including deductibles, co-payments and 


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all out-of-pocket expenses. Before you agree to be in this study, you should contact your health 
insurer to see if your plan will cover the costs required as part of your participation.   
 
You and/or your insurance company will not be responsible for paying for study related items 
and services that are specifically required for this research study and are not considered part of 
the routine management of your disease, if these procedures are performed at Moffitt Cancer 
Center.   
 
During your participation in this study, the study sponsor will be responsible for providing the 
study drug, Cemiplimab, at no additional charge to you. You and/or your insurance company will 
be responsible for the charges related to the administration of the study drug. 
If you would like more information on the costs of being on this study or have other insurance 
related questions then please let your clinical trial coordinator know or contact our Business 
Office at 813-745-8422. 
 
WILL BEING IN THIS STUDY HELP ME? 
You may benefit as a result of your participation in this study.  There is, however, no guarantee 
that you will benefit from your participation in this study.  Information learned from the study may 
help other people in the future. 
 
ARE THERE RISKS TO ME IF I AM IN THIS STUDY? 
The Cemiplimab might not help. 
Right now, we do not know for sure if Cemiplimab will help.  If it does not help, your 
condition/disease may get worse. 
You may have problems because of the Cemiplimab.  These problems are called side effects.  
Some side effects are just bothersome.  Others could harm you.  There may be some side 
effects that we do not know about yet.  The research might involve risks to you that are currently 
unforeseeable.  Your health care team may give you medicines to help lessen side effects.  
Many side effects go away soon after you stop taking the study drug.  In some cases, side 
effects can be serious, long lasting, or may never go away. There may also be the risk of death. 
 
HERE ARE THE KNOWN SIDE EFFECTS THAT COULD HAPPEN WITH CEMIPLIMAB 
Risks and side effects related to the Cemiplimab include those which are: 
Most Common (more than 10% of participants)  
• 
Fatigue (tiredness) 
• 
Rash 
Common (1 to 10% of participants) 
• 
Nausea (feeling sick to your stomach) 
• 
Diarrhea 


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• 
Arthralgia (joint pain) 
• 
Itchiness 
• 
Damage to the liver (from inflammation) that causes an abnormal result on a blood test 
of liver function and may cause symptoms 
• 
Underactive or overactive thyroid gland (which can cause tiredness, constipation, hair 
loss, sensitivity to heat or cold temperatures, mood changes, sweating, muscle aches, a 
fast heartbeat or weight changes) 
• 
Decreased appetite 
• 
Fever 
• 
Infusion-related reaction 
• 
Myalgia (muscle pain) 
• 
Asthenia (weakness or lack of energy) 
• 
Chills 
• 
Pneumonitis (inflammation of the lung) which may be life-threatening or may lead to 
death 
• 
Vomiting 
• 
Dry mouth 
• 
Headache 
• 
Dry Skin 
• 
Cough 
• 
Stomatitis (inflammation of mouth and lips) 
• 
Anemia (low red blood cells that can cause tiredness, physical weakness or lack of 
energy) 
• 
Abdominal (stomach) pain 
• 
Dizziness 
• 
Constipation 
• 
Flu-like illness 
• 
Insomnia (trouble sleeping) 
• 
Shortness of breath 
• 
Low white blood cells (that can make it more likely to get an infection) 
• 
Swelling of arms or legs  
• 
Blood creatinine increased which indicates impaired kidney function or kidney disease 
Rare and serious (less than 1% of participants) 
• 
Encephalitis (inflammation of the brain) which may result in severe memory loss and 
occasionally death. 
• 
Myasthenia gravis, a disease that causes muscle weakness 
• 
Colitis, an inflammation of the colon 
• 
Diabetic ketoacidosis, a severe complication of diabetes (high blood sugar) where the 
body makes too much acid in the blood 
• 
Diabetes mellitus 
• 
Hypophysitis, pituitary gland inflammation (possible headaches) 
• 
Myocarditis, inflammation of the heart muscle 


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• 
Meningitis, inflammation of the membrane around the spinal cord and brain (possible 
headache and/or coma) 
• 
Guillain-Barre syndrome, damage to the nervous system (causing numbness and/or 
paralysis) 
• 
Pancreatitis, inflammation of the pancreas causing pain in the upper abdomen. This 
could become severe and cause nausea and vomiting, fever and rapid heart rate 
• 
Pemphigoid, large skin blisters 
• 
Adrenal insufficiency/Adrenocorticotropic hormone deficiency: Adrenal gland does not 
produce enough of certain hormones  
• 
Pericarditis: inflammation of the pericardium which is two thin layers of a sac-like tissue 
that surround the heart  
• 
Myositis: inflammation of the muscles 
Cemiplimab can cause some type of side effects called immune-related adverse reactions. 
These immune-related side effects can be serious and require corticosteroid treatment and 
interruption or discontinuation of study treatment. It is important to contact your study doctor 
immediately if you experience any of these symptoms described below or if they get worse:   
• 
Pneumonitis (inflammation of the lung): new or worsening cough, chest pain, or 
shortness of breath. 
• 
Colitis (inflammation of the colon): diarrhea, blood in stool or severe abdominal pain  
• 
Hepatitis (inflammation of the liver): jaundice (yellowing of skin, mucus membranes or 
whites of eyes), severe nausea or vomiting, or easy bruising or bleeding  
• 
Hypophysitis (inflammation of pituitary gland which secretes hormones to control several 
body processes): persistent or unusual headache, extreme weakness, dizziness or 
fainting, vision changes, or other changes due to an effect on your hormones 
• 
Nephritis (inflammation of the kidney): pain in pelvis, pain or burning during urination, 
frequent urination, blood in urine, vomiting, fever  
• 
Hyperthyroidism and Hypothyroidism (over or underactive thyroid gland): tiredness, 
weight gain or loss, hair loss, constipation, depression, irritability, muscle aches, 
intolerance to heat or cold 
• 
Uveitis (inflammation of the eye): eye redness, eye pain, light sensitivity, blurred vision, 
floaters, decreased vision  
• 
Skin changes: peeling of the skin over large areas of the body, rash, itching, skin 
blistering. 
• 
Mucositis (painful inflammation and ulceration of mucous membranes lining the digestive 
tract): painful sores in the mouth, tongue, nose or throat which can make it hard to eat or 
drink 
• 
Encephalitis (inflammation of the brain): headache, fever, tiredness, confusion, memory 
problems, sleepiness, seeing or hearing things that are not really there, seizures, stiff 
neck 
 


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ALTERNATIVE TREATMENTS 
Some potential alternatives to participating in the study are palliative chemotherapy or 
cetuximab.  
As with any medication or chemotherapy treatment, there may be risks, known and unknown. 
The most common temporary side effects for some chemotherapy drugs may include nausea 
and vomiting, loss of appetite, hair loss, mouth sores, higher risk of infection (due to decreased 
white blood cells), bruising or bleeding, fatigue (feeling tired), and changes in your menstrual 
cycle if you are a woman, (such as, irregular periods or symptoms of menopause [end of 
menstruation]). 
A more complete listing of side effects for other therapies may be available for you to review if 
you wish.  Please talk with your study doctor about the risks of both this investigational drug and 
any alternative methods of treatment that are available. 
 
WHAT CAN HAPPEN IF I GET INFUSIONS? 
The study doctor will give you the study drug by sticking a needle in your skin.  Some problems 
you might have from this are: 
• 
Pain 
• 
Bruising 
• 
Dizziness 
• 
Infection 
You will receive the study drug intravenously, which means you will receive it directly into your 
vein.  This may cause the following problems: 
• 
Irritation of the vein; your skin near the vein could become warm, swell, hurt, or get red 
• 
Damage to your vein 
• 
Damage to the skin or tissue around the injection site 
• 
Too much of the study drug may be given to you 
• 
An increase or decrease in electrolyte levels (the amount of certain salts and other 
chemicals in your blood), could occur which could cause health problems 
• 
A blood clot or an air bubble could form, which could block a blood vessel in another part 
of your body 
Some of these problems could be very serious. 
Over time, getting a lot of injections can cause a vein to become hard or scar, which can make it 
difficult to put a needle into the vein to give you a shot or take blood. 
 
COULD I HAVE AN ALLERGIC REACTION? 
Occasionally, people have allergic reactions to medications which may require medical 
treatment.  A severe allergic reaction could be life-threatening.  Examples of an allergic reaction 
include: a rash; shortness of breath; wheezing; difficulty breathing; sudden drop in blood 
pressure; swelling around the mouth, throat, or eye; fast pulse; and sweating.  You should get 


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immediate medical help and contact the study doctor if you have any of these or any other side 
effects during the study. 
 
IS THERE ANY RISK TO YOUR UNBORN CHILDREN IF YOU TAKE PART IN THIS STUDY? 
FOR WOMEN: 
If you are pregnant, you cannot participate in this study, because there may be risks to you and 
your unborn baby that are currently unforeseeable; risks that we do not know about yet.  
Breastfeeding (nursing) mothers will not be included in this study, since it is not known whether 
the study drug will be passed on to the baby in mother’s milk.  If you are currently breastfeeding 
and wish to continue breastfeeding, your study doctor may recommend another treatment. 
If you are a woman of childbearing potential (able to become pregnant), you will be given a 
pregnancy test before beginning any study drug. 
Tell the study doctor right away if: 
• 
You are pregnant. 
• 
You become pregnant. 
• 
You are planning to become pregnant. 
• 
You are breastfeeding. 
FOR MEN AND WOMEN: 
Whether you are a man or a woman, there may be risks to your unborn children that we don’t 
know about ahead of time; they are unforeseeable. 
If you take part in this study, you must use an effective birth control method as discussed with 
your study doctor and continue to use it until at least 6 months after your last dose of study 
drug. 
Examples of birth control methods include: 
• 
Oral birth control pills 
• 
Birth control patch 
• 
Implanted (injectable contraceptive hormones or mechanical products such as 
intrauterine device) 
• 
Barrier methods (such as: diaphragm, condoms, or spermicides) 
• 
Tubal ligation or vasectomy 
• 
Abstinence (no sexual intercourse) 
You should discuss the method of birth control which is best for you to use both during study 
treatment and for a period of time after study treatment. 
Whether you are a woman or a man, you should tell your study doctor immediately if you 
become pregnant or if your partner becomes pregnant.  Women who become pregnant during 
the study will have to leave the study.   
The long-term effects of the study drug on fertility are unknown.  This means that it is unknown if 
the study drug will affect your ability to have children in the future.  If we find out that the study 
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Cancer treatment can affect fertility in both men and women, and it is important to understand 
the risks before starting study therapy.  Ask your study staff about fertility preservation before 
you begin study treatment.  However, once you have started study treatment you should not 
donate or sell your eggs or sperm. 
 
COULD I HAVE ANY OTHER PROBLEMS WITH MY HEALTH IF I DO THIS RESEARCH 
STUDY? 
It is possible that you could have problems and side effects of Cemiplimab that nobody knows 
about yet, which include your cancer getting worse or even death.  If the study doctor learns any 
new 
 information that might change your mind about continuing in the study, the study doctor or 
study staff will tell you about it.  The study doctor will also tell you if new treatments become 
available for your cancer. 
It is possible that taking Cemiplimab with your regular medications or supplements may change 
how, the study drug or your regular medications, or regular supplements work.  It is very 
important that you tell the study doctor about all medications or supplements you are taking 
during the study. 
 
WHAT ARE THE RISKS OF GIVING BLOOD FOR THIS STUDY? 
Risks associated with drawing blood from your arm include momentary discomfort and/or 
bruising.  Infection, excess bleeding, clotting, or fainting are also possible, although unlikely. 
You will give about 20 ml (4 teaspoons) of blood for research purposes at screening, at the start 
of cycles 3, 6, 9 and 12, at End of Study Treatment (EOST), and End of Study (2 years after 
your first study treatment).  In total, this will amount to approximately 140 ml (about 9 
tablespoons) of blood.  
 
WHAT ARE THE RISKS OF HAVING A BIOPSY DONE FOR THIS STUDY? 
Optional Tumor Biopsy 
Risks of a tumor biopsy are localized bleeding at the needle injection site or from the surgical 
incision, pain, inflammation, swelling, and infection.  The bleeding may cause discomfort and 
bruising.  In rare circumstances (less than 1%), this bleeding may be severe enough to require 
further care.  If you have a history of excessive bleeding, or if you are receiving medication that 
might increase your risk of bleeding (such as aspirin or blood thinners), you must notify the 
study doctor before the procedure.  Infection of the surgical site may require treatment with 
antibiotics. 
Tumors that are biopsied from the lungs may result in an additional risk of pneumothorax 
(collapsed lung).  Biopsies in or near other vital organs may result in bleeding that can be life-
threatening or may cause damage to the organs and affect their function.   
Depending on the site, the biopsy procedure may use local anesthetics (numbing medicine), 
sedatives, or general anesthesia to reduce the discomfort or pain.  All medicines have the 


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possible risk of allergic reaction.  Please advise your study doctor if you have ever had an 
allergic reaction to latex, lidocaine, or any other anesthetic.   
Any complications arising from the biopsy may be treated with observation, additional 
medications, or in some cases, additional surgery.  The study doctor will discuss the specific 
risks of the biopsy with you at the time of the procedure. 
Liver Biopsy 
For participants undergoing an optional liver biopsy, there may be increased risk in certain 
circumstances.  When study doctors perform your liver biopsy, they do so by passing a needle 
into the liver usually through your side.  Doctors are usually able to get a large enough piece of 
liver to examine under the microscope by taking a single biopsy of the liver.  However, in some 
participants, only a small piece is retrieved (not enough to look at under the microscope) and in 
this case, a second specimen from the liver is taken for clinical diagnosis.  However, after the 
first attempt, if there is enough for clinical purposes, but not for research purposes, a second 
piece will be taken for research purposes.  Thus, by participating in this study, in a small fraction 
of participants undergoing liver biopsy (less than 5% of all participants), there will be a chance 
that a second piece of liver will be taken for research purposes.  The additional risk of an 
additional liver sampling is approximately 1 in 1,000 for increased bleeding, and 1 in 2,000 for 
other complications such as puncture of a lung or colon.  These complications are managed by 
observation and, in some circumstances, surgery. 
Skin Biopsy 
A skin biopsy is generally a non-hazardous procedure; however, possible hazards may include: 
1) reaction to anesthetic (numbing medicine), 2) excessive bleeding, 3) bruising, 4) infection and 
5) excessive scarring.  While the local numbing medicine xylocaine is almost entirely free from 
allergic properties (such as causing hives), an allergic reaction is possible, and you will not be 
given xylocaine if you have a history of such a reaction.  The xylocaine will be given by a small 
injection into the skin at the site of the skin biopsy.  To speed healing, one or two stitches (also 
known as sutures) will be placed, which will be removed 5 - 7 days later.  During the healing 
process, you will be asked to keep the biopsy site clean and dry, and to apply antibiotic 
ointment.  Infection rarely occurs and is largely prevented by the use of an aseptic (or sterile) 
biopsy technique and proper wound care. If infection does occur, you will be instructed to keep 
the wound clean and to apply warm, wet compresses for 15 minutes, three times a day, until the 
infection subsides.  If the infection persists, antibiotics may be prescribed. 
Only 10-15 minutes will be required for the biopsy procedure.  After the anesthesia wears off, 
there will be some soreness at the biopsy site that will last for a few hours.  A small scar will 
develop at the site of the biopsy. 
 
WHAT ARE THE RISKS OF OTHER STUDY PROCEDURES? 
MRI 
Magnetic resonance imaging (MRI) uses a magnet and radio waves to make diagnostic medical 
images of the body.  There have been no ill effects reported from exposure to the magnetism or 
radio waves used in this test.  However, it is possible that harmful effects could be recognized in 
the future.  A known risk is that the magnet could attract certain kinds of metal.  Therefore, we 
will ask you about metal within your body, including medical implants, devices such as 


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pacemakers and internal defibrillators, or certain dyes found in tattoos.  We will also keep the 
examining room locked so that no one carrying metal objects can enter while you are in the 
scanner. 
If there is any question about potentially hazardous metal within your body, you will not undergo 
the MRI.  This may exclude you from participation in this research study.  The MRI involves 
entering a large room in which a magnet is present.  You will be placed on a narrow bed and 
then slid into a small tunnel approximately 6 feet in length and 25 inches in diameter.  You will 
be asked to lie still for about one hour on this bed.  You will hear a loud machine-like noise.  You 
may be asked to have a harmless monitoring device applied during the MRI.  During the MRI, 
you can have voice contact and physical contact with someone in attendance if you desire.  Let 
the study doctor know if you have a fear of enclosed spaces. 
CT Scan 
Computed Tomography (CT) is a way to make x-ray images of the inside of the body.  The CT 
scanner is a doughnut-shaped machine that uses x-rays to create computer pictures that show 
structures inside your body more clearly than regular x-ray pictures.  During the procedure, a 
technologist will take you into the CT scan room where you will lie down on the table (usually on 
your back) inside of the CT machine.  You should get comfortable because it is very important 
that you not move during certain parts of the test. 
CT examinations differ depending on the part of your body being studied.  For example, if your 
abdomen is being studied, a series of pictures will be taken from your lower chest to your lower 
pelvis.  During the study, you will be asked to hold your breath so that the pictures will not be 
blurred.  The machine will make some noise, and the table will move during the scan.  Also, you 
may receive signals from the technologist or from the machine about your breathing.  Before or 
during the study, you may be given an injection of a contrast liquid in your vein to allow the 
radiologist to obtain clearer images of your organs.  If you have any discomfort during the test or 
after the injection, be sure to tell the technologist. 
Confidentiality 
There is a risk of loss of confidentiality of your information.  You will read more about the 
protection of your information later in this form.  Please ask the study doctor or study staff if you 
would like to know more about how your information will be protected while you are in this study. 
 
WHAT IF I GET HURT OR SICK WHILE I AM IN THIS STUDY? 
If you need emergency care: 
• 
Call 911 or go to your nearest emergency room right away. Moffitt Cancer Center does 
not have an emergency room or the facilities to provide emergency care. 
If you do NOT need emergency care: 
• 
Call or go to your regular doctor.  It is important that you tell your regular doctor that you 
are participating in a research study.  If possible, take a copy of this consent form with 
you when you go. 
If you experience a side effect or a change in the way that you feel, call the study doctor at the 
telephone number listed on the first page of this form. 


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By signing and dating this informed consent and research authorization form, you have not 
given up any legal rights to seek compensation for injuries from the sponsor. 
 
MOFFITT CANCER CENTER INJURY STATEMENT 
If you believe you have been injured as a result of your participation in this study or if you have 
questions about your rights as a person who is taking part in a research study, you may call the 
Moffitt Cancer Center Risk Manager at 813-745-7882.  Moffitt Cancer Center and its 
investigators have made no provision for monetary compensation in the event of physical illness 
or injury resulting from this study.  Likewise, Moffitt Cancer Center and its investigators have 
made no provision for payment of lost wages, disability, or discomfort in the event of physical 
illness or injury resulting from this study.  Florida law (Statute 768.28) limits the liability of Moffitt 
Cancer Center.  This statute provides that damages are available only to the extent that 
negligent conduct of a Moffitt Cancer Center employee caused your injuries, and are limited by 
law. 
 
WILL I GET PAID? 
You will not get paid for being in this study.  You will not be reimbursed for expenses for travel 
and/or lodging while taking part in this study. 
 
WHILE YOU ARE IN THE STUDY, YOU MUST: 
• 
Follow the instructions you are given. 
• 
Come to the study center for all visits with the study doctor. 
• 
Give correct and accurate information about your medical history and current medical 
condition. 
• 
Tell the study doctor about any health problems you have during the study. 
• 
Tell the study doctor about any new medicine or drug you take during the study. 
• 
Not take any other drugs or remedies unless the study doctor has approved them 
beforehand.  This includes prescription drugs and over the counter medicine (including 
vitamins and herbal remedies) that you buy without a prescription. 
• 
Not participate in other medical research studies. 
• 
Not get pregnant or cause your partner to become pregnant. 
• 
Tell the study doctor or study staff if you want to stop being in the study at any time. 
 
DO I HAVE TO REMAIN ON THIS STUDY ONCE I JOIN? 
If you want to stop being in the study, tell the study doctor or study staff.  If you stop being in the 
study early, the study doctor or study staff may ask you some questions about being in the 
study.  To help you leave the study safely, the study doctor may ask you to participate in more 
tests or return for a final study visit. 
 


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ARE THERE REASONS THE STUDY DOCTOR OR SPONSOR MIGHT TAKE ME OUT OF 
THE STUDY LATER? 
Even if you want to stay in the study, there may be reasons the study doctor or study staff will 
need to take you out of it.  Your study doctor has the right to take you out of the study at any 
time with or without your agreement.  Your participation may be ended without your consent for 
different reasons, including the following: 
• 
If the study doctor believes, for any reason, that it is in your best interest. 
• 
If at any time while you are taking the study drug the study doctor discovers that your 
disease has worsened. 
• 
If you develop side effects that the study doctor considers unacceptable. 
• 
If you refuse to take the study drug or return for follow-up as recommended by your 
study doctor, or do not follow the study doctor’s instructions. 
• 
If you refuse to have tests that are needed to determine whether the study drug is safe 
and effective. 
• 
If you require treatment with drugs that are not allowed on this study. 
• 
If other causes prevent you from continuing in this study. 
• 
If the Sponsor decides to end the study. 
 
HOW WILL MY INFORMATION BE KEPT CONFIDENTIAL? 
We understand that information about you and your health is personal, and we are committed to 
protecting the privacy of that information.  Because of this commitment and because of federal 
law, we must obtain your written authorization before we use or disclose your information for 
this study. 
By signing and dating this form, you are permitting researchers at Moffitt Cancer Center to use 
personal health information for research purposes within its organized health care 
arrangements.  You are also allowing the Moffitt Cancer Center to disclose your personal health 
information to outside organizations or individuals that participate in this study.  We may publish 
what we find out from this study.  If we do, we will not let anyone know your name.  We will not 
publish anything that would directly let people know who you are. 
Identifiers might be removed from your identifiable private information or identifiable 
biospecimens collected during this study and could then be used for future research studies or 
distributed to another investigator for future research studies without additional informed 
consent. 
 
WHO WILL DISCLOSE, RECEIVE, AND/OR USE YOUR INFORMATION? 
Your records are confidential and they will be kept in a secure environment and protected to the 
full extent of the law. 
To do this research, the following people and/or organization(s) will be allowed to disclose, use, 
and receive your information, but they may only use and disclose the information to the other 
parties on this list, to you or your personal representative, or as permitted by law: 


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• 
Every research site for this study, including the Moffitt Cancer Center, and each site’s 
study team, research staff and medical staff. 
• 
Any person who provides services or oversight responsibilities in connection with this 
study. 
• 
Every member of the Moffitt Cancer Center workforce who provides services in 
connection with this study. 
• 
The person who is responsible for the study nationwide or worldwide (study 
chairperson). 
• 
Any laboratories, individuals, and organizations that use your health information in 
connection with this study. 
• 
Any funding source of the study, including Regeneron Pharmaceuticals, Inc. 
• 
Any federal, state, or local governmental agency that regulates the study (such as the 
U.S. Food and Drug Administration (FDA) and Florida Department of Health (FDH). The 
U.S. Department of Health & Human Services (DHHS), Office for Human Research 
Protections (OHRP). 
• 
Other government agencies in this or other countries. 
• 
The designated Protocol Review and Monitoring Committees, Institutional Review 
Boards such as Advarra IRB, Privacy Boards, Data and Safety Monitoring Board and 
their related staff that have oversight responsibilities for this study. 
• 
The National Cancer Institute in evaluating the ongoing research of the Moffitt Cancer 
Center as a Comprehensive Cancer Center. 
The organizations and people listed above may employ or pay various consultants and 
companies to help them understand, analyze and conduct this study.  All of these people may 
not be known now, but if you would like to have more specific information about this at any time 
during the study, you may ask the study doctor and your questions will be answered. 
Moffitt Cancer Center cannot guarantee the privacy of your information, or block further use or 
distribution, after the information has left the Moffitt Cancer Center.  Others listed above may 
further disclose your information, and it may no longer be covered by federal privacy 
regulations.  If all information that does or can identify you is removed from your records, the 
remaining information will no longer be subject to this authorization and may be used or shared 
for other purposes.  You might have the right to see and copy your health records related to this 
research.  You might not be able to see or copy some of your records until after all participants 
finish the study.  If it is necessary for your care, your records will be provided to you or your 
regular doctor. 
 
WHAT INFORMATION WILL BE USED OR DISCLOSED? 
By signing and dating below, you authorize the use and disclosure of your entire study record 
and any medical or other records held by Moffitt Cancer Center, including, but not limited to, 
HIV/AIDS, mental health, substance abuse or genetic information.  The purpose for the uses 
and disclosures you are authorizing is to conduct the study explained to you during the informed 
consent and research authorization process and to ensure that the information relating to that 
study is available to all parties who may need it for research purposes. 
Your authorization to use your health information will never expire unless and until you 
expressly revoke it in writing to the study doctor listed on the first page of this form. 


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Any data collected before your letter will continue to be used as necessary to preserve the 
integrity of the study, however no additional information will be collected after you withdraw your 
authorization. 
You will receive a signed and dated copy of this form. 
 
WHOM TO CONTACT ABOUT THIS STUDY 
During the study, if you experience any medical problems, suffer a research-related injury, or 
have questions, concerns or complaints about the study, please contact the Investigator at the 
telephone number listed on the first page of this consent document.  If you seek emergency 
care, or hospitalization is required, alert the treating physician that you are participating in this 
research study. 
An institutional review board (IRB) is an independent committee established to help protect the 
rights of research participants.  If you have any questions about your rights as a research 
participant, and/or concerns or complaints regarding this research study, contact: 
• 
By mail: 
Study Participant Adviser 
Advarra IRB 
6940 Columbia Gateway Drive, Suite 110 
Columbia, MD 21046 
• 
or call toll free: 
877-992-4724 
• 
or by email: 
adviser@advarra.com 
Please reference the following number when contacting the Study Participant Adviser: 
Pro00037712. 
 
WHERE CAN I GET MORE INFORMATION? 
You may call the National Cancer Institute’s (NCI) Information Service at: 
 
1-800-4-CANCER (1-800-422-6237). 
Visit the NCI’s Websites at: 
• 
CancerTrials: comprehensive clinical trial information at: http://cancertrials.nci.nih.gov 
• 
CancerNet: accurate cancer information including PDQ at:  http://cancernet.nci.nih.gov 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by 
U.S. Law.  This Web site will not include information that can identify you.  At most, the Web site 
will include a summary of the results.  You can search this Web site at any time. 


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CONSENT FOR OPTIONAL TUMOR BIOPSIES 
 
Participant’s Initials ______ Yes, I agree to the optional tumor biopsies outlined in this consent 
form (1 to be performed at screening and 1 to be performed at the end of the study) and for the 
use of my biopsy samples in future research.  
 
Participant’s Initials ______ No. I do not agree to the optional tumor biopsies. 
 
STATEMENT OF CONSENT AND AUTHORIZATION 
I have read this form and its contents were explained to me.  I agree to be in this research study 
for the purposes listed above.  All of my questions were answered to my satisfaction.  I will 
receive a signed and dated copy of this form for my records. 
 
 
_______________________________________________ 
Printed Name of Participant  
 
 
_______________________________________________________________ 
 
Signature of Participant                         
Date                Time 
 
                     
 
STATEMENT OF PERSON OBTAINING INFORMED CONSENT / RESEARCH 
AUTHORIZATION 
I attest that the participant named above had enough time to consider this information, had an 
opportunity to ask questions, and voluntarily agreed to be in this study. 
 
 
_______________________________________________ 
Printed Name of Person Explaining Consent 
 
 
 
________________________________________________________________ 
Signature of Person Explaining Consent                 
 Date                 Time