Clinical trial: NCT04163952
Section: Alternatives
Subsections: What Is Stsndard Of C*Re?

Several agents including cemiplirnab, EGFR inhibitors like fyrosine kiuase inhibitors (e-g-'
erlotinib. gefrtinib) andbCn'trmonoclonal antibodies (e.g., cetrrximab, necitumtuuabn paninrmumab alone) or chernotherapy can be enrployed in locally advanced disease.  
Other options ilclude treahneut with irnmunotherapy such as cemipliurab, which can produce
,"rpo*"r. Not all patients are candidates for cemiplimftb and this ueeds to be discussed with you doctor. Palliative care options can be considered.
Clinical trial: NCT04163952
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: Injection Sife Reactious|Cellulitis|Flu-Like S).Mptoms|Skin Toxieity|Scarring Of Hurg|Infirsion Reactions|Are There Any Other Risks?|Physical Risks Of Hamt:|Reproductiye Risks

Talimogeue laherparepvec is admiuistered by direct injection into skin turuor masses. lnjection site adverse events lnay occur, such as lgddsning of the skin, local skiu discoloration" hardening of soft tissue, waruth. and pain. Less fiequently, iajected skin hmor masses may become open wounds, predisposing you to local an\#or systernic infections. $inrilar:ly, injected nodes may eularge or become uecrotic death of cells or tisstres). Adverse events of "injectiou site pain" aad
"injectiol site reactiol" were very sormron, occuning irr >l0oz'o of Taliurogene laherparepvec-  
  
Shdy Tifle: A phase I of Talinrogene Laherparepvec and Pauihumutrab in Patients with Locally Advaficed Squarnous cell carcinoma of tbe skin (sccS)
and injection site reactiou rvere miltl to heated subjects. Most events of injection site moderate in severitypaiu

Death of body tissue of skin tumor masses and diseased lymph nodes injected rvith Taliroogene lahe.rparepvec may ilfrequently occrr, predisposing to local/regpon*l infection (i.e., cellulitis). In clinical studies fo date, cellulitis was coulruon, occurring in > l7o to < 10Yo of subjects teated with Talimogene laherparepvec.

Syruptomi incltrding chills, fatigue, headache. nruscle pain, zurd fever may occru with Talimogene laherparepvec. In clinical studies to date, adverse eveuts "chills". "fatigple",
"headac-he", *iufluelza like illness", "ttluscle pflh", arrd "fever" were very corrrnroll, occurring in
> l0% of subjects treated with Talimogene laherparepvec. Most of these events were urild to moderate in severity.  
Accidental Expostue A""i.l"rtul "xposure uray lead to tralsmission of Taliurogene lalrerparepvec and herpetic infection.  
Caregivers should wear protective gloves when assisting you ir applying or clranging occlusive dressings (bandage) and observe safety precautions for disposal of used ibsssings, gloves, aud cleaning materials. Spreading talimogene laherparepvec may be more likely if yoru close contact has a break in the skin or rlucous urembranes that comes into contact with you injection site or you body fluids. In patients treated with talirnogene laherpalepvec in clinicai trials, taliruogene iulr"rp*"p""" has been fourd ou tlre stuface of the injected turuors and on the outside of the dressings that covered these injectiol sites.  
Talimogene laherparepvec have also been deteeted in patieuts' blood and ruine, and in the patient's mucous rnembraues of the mouth and genilals, no sarnples had detectabletalimogeue iaherparepvec 30 days after the end of treatment. For patients who had talimogene laherparepvec pr"r"o"" i1the surface of injected huxors. no samples had detectable talimogene laherparepvec 60 days after eud of treatmeut.  
I1the event of an accidental exposure to talimogene laherpatepvec" exposed i[dividuals should cleal the affected area thoroughly with soap artd water and/or a disitfectant. If sigrrs or symptorns of herpetic infection develop, the exposed iadividuals should contact thefu'healthcare provider for appropriate treahuent.  
You should avoid togching or scratching injection sites or their occhrsive dressings, as doirig so could lead to inadvertent tmnsfer of talir:rogene laherparepvec to other areas of the body.  
  
Shrdy Title: A Phase I of Talinrogene Laherparepvec and Panituuuuuab in Patienfs lvith Locally Advanced squarnous cell carcifloua of the skin (sccs)
,r-

Skin toxicities occurred tn 90ols of patieuts and were severe in 15o/o of patients receivifig panitlmumab. The clinical synlptoms inchrded acne like rash. itchy skin, reddeuing of the skin, iash. skin peeling, nail disease, dry skin, and tear in the skirr. You are advised to avoid sun exposure while receiving panifumtunab.

S.*r--g of lturg may be acute in otset and has beel observed in 1.3% of patients, and some cases have been fatal.  
Chemical aud Mineral Abnonualities Pr"S.r""-ty decreasing serum magnesium levels leading to severe low maguesium (a mifleral in yoru blood) occtured iu .rp to 7o/o of patietts across clinical hials. Other chemical dishu'bances have also been observed.

f" o"" .toay, 4olo of patients receiving panihrmumab experienced infusion reactiotrs, and l% of patients experienced severe infusion reactions. Infusion reaction synptoms inelude fevers,
"hill*,
difflculfy breathing, tigilrtering of the airways in the lurgs. and low bloodpressure.  
  
  
  
Photosensitivitv E-p**= i" -,*light can worserl skiu toxicity. You are advised to lvear stuxcreen and hats, aud limit stur exposrue while receiving paniturntuuab.  
Ocular Toxicities Ke.rafitis (iuflamed eye's comea) and uleerative keratitis are botl known risk factors tearilg, and keratorhexis (coureal perforation) have beeu reported with panitumurnab-for corneal Other Toxicities Lfe-ttueaiemng and fatal infectious conrplications including inflanunation. collection of pus' and infection have been observed inpatients treated with panifumumab.  
Life-threatening and fatal blisters, etosions, and skin peeling has also been obsenred in patients treated with paninrmumab.  
Yoru conditiol may not irnprove ald could even worset if you take part in this shldy' The sfudy does have risks. becarme the treahuent is investigational, we ruay not yet lorow all the side effects: sornething turexpected could happen.

Otlrer less commol side effects have been reported with the use of the drugs in this study- The study doctor or staffcan discuss these with you-
There may be other side effects or risks that are not known at this time.  
As with all medications, the side eifects or risks described umy occ:ur ruore ofteu or be ruore severe than has beea seen before.

o From Biopsies, you tnay exPerielce:
e Pain and discourfort at the biopsy site o Minor bleeding at the biopsy site o Tenderness at the biopsY site r Scarring at the biopsy site o Rarely, an infection at the biopsy site. *I
Shldy Tifle: A phase I of Talimogene Laherparepvec and Panitumtuuab in Patienfs with
' Locally Advanced Squaruoirs Cell Carcino'ra of the Skin (SCCS)

Panifumlmab and talimogene laherparepvec may have adverse effects on a fehrs in utero.  
Ftlthennore, it is lot known if panitruntrmab and talimogene laherparepvec have trausient adverse effects on tlre composiiion of spenn. It is wrknowu whether panitumumab and talimogene traherparepvec areixcreted in human milk. Since rnany drugs ate excreted in lrtlnan rnilk, panittrmunab and Taliurogene laherparepvec have the potential for serious adveme reactioos in the nrusiug infant.
Clinical trial: NCT04163952
Section: Procedures
Subsections: What Wilt T Be Asked Io Rlo If I Take Part In This Research Study?|While An Sftuly Treatment:|About Tests, Procedures, Ai$D Intervention

Before );ou begin studlt treatment:
If you apgee to take part in this study, you will fust sign this "Subject Coasent to take part in a resealch shrdy" before any study-related procedures are perfor:ned, iuchrding stopping use of medication not allowed in this study.  
Before you arc enrolled it the study, you will undergo cerlain tests to enstue that it is safe for you to go on the sfudy- Most of these exftrus, tests, or procedtues are part of regrilar cancer cat-e and may be doue ever if you do not take part in this study. If you have had some of these tests receutly, they may not reed to be repeated. Tlrese tests and procedures, for example baseliue laboratory, blood tests. and EKG (electocardiogram), need to be done withio t4 days before you receive yotu'first sh.rdy h'eatment. Tests such as hunor assessrnent (evaluation of cancer disease),
radiology scan tests, ard first tumor biopsy need to be done withitr 30 days of yotu' first study treahnent.

When all of the above tests have been completed, you have been fotmd eligible to enter this study, and you aepe€ to participate, you will be scheduled to beeir treatment ot this study.  
o You will receive study dnrg as below.  
r Talimogene laherparepvec will be administered as a single agent on day 1 (week l), and thereafter in conrbination with Panihunuurab on day 22 (week 4), and to be continued on weeks 6, ald every 2 weeks thereafter.  
- The fotal volume of Talirnogene laherparepvec to be injected will be based on investigator evaluation of injectable lesions and tumor size. The maximtun vohune of

\ilhat effects, risks, and discomfort cotrld the tests have oa me?  
  
You may feel discomfort during some of these tests or may experience sorue ircouveniences.  
Some may also have risks, which may include:
Page 13 of3l Shrdy Title: A phase I of Talirirogene Laherparepvec aud Panitumuurab irr Patients with Locally Adva,ced Sq*aruoirs Cell Ca'cino,ra of t6e Skin (SCCS) tr,E
o Blood samples: drawing blood &om your exftemity (anu or leg) may catrse pain' bnrising, ligbtlreaded-ness, and rarely, infection.  
o Estimated Total Blood Draws:
. Treatment Phase: 200 ml (about 7 orurces)
o IV Line: placement of an inhavenous line for infusion of the study drug ilray cause discomfoit, irritation, mild bruising, bleedirg, and rarely infection, nausea, and ligbtheadedness. Because panihrmumab is an antibody, there is the possibllity that you may eiperience an acute infusion reaction. These are side effects that develop dtuing or immediately a*er the adurinistration ofpanihmnunab.Signs and symptoms rnay include:
o Blood presstue changes (increase or decrease)
o Couglr o Dizziness o Fastheartbeat o Feeling cold o Feeligg that the tongue is swelling or yoru airway is closilg and you have trouble breathing o Fever o Headache o Joint pains D Muscle pains o Nausea o Rash, hives, or itcl'ring o Shortness of breath o Sweating o Tiredness o Vomiting o Tgmor Biopsy: A biopsy will be used to determine how your irnrnune system is responding to the tueahnent. the biopsy will be doue at baseline prior to treatmeut beginning' at completion of therapy (J surgery if surgery is ptrsued; if surgery is not recommended, a second biopsy will ie oUtd""al *d within 30 days of huuor recurrerce. The hrmor will be sent to "."rtul laboratory for testing andwill not be a part of your medical record-
Clinical trial: NCT04163952
Section: Purpose of Research
Subsections: Why Is This Study Being Tlone?

The prupose of this shrdy is to:
o Primary:
o To detemrine the safety of the combined heafunent of Talimogeue laherparepvec and panitumumab.  
o To determine fhe prelirninary effectiveness (also krown as efficacy) of the combined treatrnent of Talimogene laherparepvec and panihrmumab. iu courparisou to single-dnrg panihrmuurab (historical effectiveness).  
o SecondarJr:
o To assess ttrre effectivetess of paniftnmunab in cornbinatiou with inhahunoral Talimogene laherparepvec in terux ofnon-advancitg or growilg (progression-fi-ee) survival at 12 months.  
o To measrxe the improvement in conditious, siggrs a,'d synrptorns sf yeru disease
(includirg whether disease has had a complele response) to pauihununab combined with Talimogene laherparepvec.  
o Assess the response of injected and non-injected hrmor sites after palihuurunab and Taliurogene laherparepvec.  
o See the time it takes to first-time (initial) response.  
o See how long responses to the dnrgs last.  
This is a research study to test dnrgs (panitumtunab and Taliruogene laherparepvec) that have been approved for use in cerlaiu fypes of cancer. Padturnumab is FDA-approved for use in patients with wild-type RAS (defined as wild-type ia both KRAS and NRAS as deter:nired by an FDA-approved test for this use) in rnetastatic colorcctal caucer (mCRC). The safety and optimal dosing of Talimogene laherparepvec was established in melanoma. ard it is an FDA-apploved agent for mefastatic melanorrra. Howeveq these drugs have not been approved for you cancer, and are therefore, expedmental. "Experimental" uleaos that f]re sfudy drug is cuuently being tested. These drugs are not approvedby the U.S. Food and Dnrg Adrniais*ation (FDAj for treafuent of your condition.
Clinical trial: NCT04163952
Section: Voluntary Participation
Subsections: Subject Consent To Take Part In A Researcii Study|Who May Take Part In This Study? And Who May Not?|Why Have I Been Asked To Take Part In This Sfudy?

TITLE OF STLIDY:
A Phase I Study of Talimogene Laberparepvec aud Panitumuurab in Patieuts rvith Locally Advanced Squaurous Cell Carcinorna of the Skin (SCCS)  
  
STUDY SUMMARY: This consent for:n is part of an infonned cotsent process for a research shrdy ald it will provide infonuation that will help you decide whether you want to take part in this study. It is yorr choice to take part or not.  
The prupose of the research is to detennine the safety and benelif of the combined treatrnent rvith talirnogere laherparepvec (also knowu as IMLYGIC0)and parriturntuBab in patieuts with advanced squaurous cell cancer of tbe skirr" If you take parl in the research. you will be asked to sigp this docunent, go through laboratory and medieal tests to verify yoru eligibility to enter this study, receive the experimeutal courbination of drugs (Taliruogene laherparepvec and panihrmumab) and turdergo laboratory tests and study procedrues on specified days duling the study period, complete end of shrdy evaluations and tests, and participate in follow up every 12 rveeks for 2 yeals. Your Shdy Tifle: A Phase I of Talimogene Laherparepvec and Panittunrunab in Patients wifh Locally Advaflced squarnous cell carci[o[ra of the skin (sccs) Pr,I
ately 4-6 hours duling pre-study, study and end of study visits.  
Possible hanns or burdens of taking part in the study may be many side etTects or toxicities known andlor uukuown for the dnrgs you take in this study (details provided later in the document). You may feel diseornfort aud/or pain during sorne of the tests or proeedures in the strdy. Yotu eondifion uray not improve aud could even worser if you take part in this study.  
Possible beneflrts of taking part rnay be improvement in yoru conditiou and slowing or stoppilg the grorth of you carcer, if the dnrgs work. Informatiou leamed f,'om the study may help otlrer people in the frrture. However, it is possible that you rnight receive no direct personal beuefrt frorn t*king part in this shrdy.  
Alternatir.es to takitg part in the research shrdy are a rnarketed dnrg or heatment with a different investigational dmg, other chemotherapy regimens, sffgery to relieve distressing symptoms or radiation treatment, or comfort care (pain medication and other support) ot non-traditiooal uredical care.  
Yoru alternative to taking part in the research study is not to take part in it and pusue other available trcatrnent opfious as described above after talkrng with l'our physiei The irfonnatiou in this consent form will provide ruore details about the research shrdy aad what will be asked of you if you choose to take part iu it. If you have any questiols trow ot'dtuing the study, if yotr choose to take part, you should feel fi'ee to ask theur aad shotrld expect to be giveu answers you courpletely r.urdersfand. After all of your quesfions have been answered and you wish to take parl in the research shrdy, you will be asked to sigrn this consent form. You are not Siving up ary of yoru legal riglrts by apeeing to take part in this resealch or by siguing this consent form.  
Sponsor ofthe study:  
  
  
  
Ine. is the extemal of this research shrdy. As a The costs that are usually covered ilclude things such as research laboratory tests reqrrired by the shrdy and the costs of collecting all of the infomration requiled by the study.  
  
Shtdy Title: A Phase I of Talinrogene Laherparepvec and Pauitruntunab in Patients with Locally Advanced Squarnous Cell Carcinoura of the Skin (SCCS) I

If you decide that you want to be in this study and you sigu this colsent forxr, you will have some plocedures doue to see if you are eligible to be in this study. If you are eligible. yotr will be enrolled in the study.  
In order to be eligible for parlicipation in this frial, you nrust/have r)
2)
3)
Be willing and able to provide written informed conseut/assent for the trial.  
Age 18 years or g[eater.  
Microscopically confirmed skin carrcel (a type klown as SCCS) that is a) locally advalced or metastatic for which culative sugery or radiation would be difficult cr irupossible, or b) recun'ent after initial surgery, chemo&erapy, or rarliation therapy, or c)
Page 3 of31  
  
Sfudy Tifle: A Phase I Sfttdy of Talinrogene Laherparepvec and Panittuntunatr in Patienfs with Locally Advanced Squarnous Cell Carcitoura of tbe Skin (SCCS)
",Iconsidered to have aggressive feahu'es.  
4) Tunror suitable for direcf or ulhasouud-guided injection (ruore thas 10 mrrr iu diarueter).  
5) Cancer disease with daily working perfonnauce of fully active or restricted to liglht work
@rown as ECOG Perfonnance Status 0, or l. or 2).  
6) No prior treatmelt with panihumnnab or Taliruogene laherparepvec for advanced disease" 7) Adequate organ fuuction 8) Female patients of childbearilg potential should have a negative preeuarcy test withiu 72 hous prior to receiving the first dose of study medication.  
9) Feurale patients of childbearing potential should be willing to use 2 nrethods of birth control or be surgically sterile, or abstain from heterosexual activity for the cotuse of the shrdy throupfr 120 days alter the last dose of study nredication.  
l0) Male patieuts should aptree to abstinence or use of an adequate method of contraception starting with the fust dose of study therapy ttuough 120 days after the last dose of study the.rapy.
There may be reasors why you are uot allowed to take part in this study. Some of these reasons include:  
1) Age <18 years.  
2) Pregnaut womeu.  
3) Tumor not suitable for direct or ulhasomrd-puided injection.  
4) Prior heahnent with Talimogene laherparcpvec for advaaced disease.  
5) Patients with active, trncotholled iafectious iucluding active herpetie iufectious or chronie herpetic iufections rcquiring anti-viral therapy (e.g., acyclovir).  
6) Patients rvithout adequate or€Fn firnction.  
7) History of allergic reactiors attributed to corupounds of siruilal chemieal or biologic cornposifion to pauifumrunab or Taliruogene laherp{repvec.
The study doctor or staffwill discuss these and any other reasons why you rnay not be allowed to euter tlte study.

You are being asked to take part in this study because it is believed that you have a type of tutor that may respond to heatrnent with Panitrunumab and Taliruogene laherparepvec.  
How long will the study take and how many subjects will participate?  
Up to 30 people may emoll iu the study. The estirnated duratiorr of the study will be 24 to 30 months. You may receive sfudy treatment for up to two years, as long as yotu disease is not getting worse or you do not have serious side effects.  
Upon sttrdy completion or ear'ly witlrdrawal, it is important for you to speak with you shrdy doctor to arrange follow-trp care.  
Page 4 of31  
  
Title: A Phase I of Talinrogene Laherparepvec and Pa:rifiunurub in Patients with Locally Advanced Squarnous Cell Carcinoma of the Skin (SCCS) tr,I