Clinical Trials Register

Summary
EudraCT Number:	2019-001469-34
Sponsor's Protocol Code Number:	NEO-CESQ
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2020-10-22
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2019-001469-34

A.3

Full title of the trial

A phase II, single arm study investigating neoadjuvant plus adjuvant treatment with Cemiplimab in high risk, surgically resectable, stage III Cutaneaous Squamous Cell Carcinoma

Studio di fase II, a singolo braccio su trattamento neo-adiuvante più adiuvante con cemiplimab nel carcinoma cutaneo a cellule squamose di stadio III, ad alto rischio, resecabile chirurgicamente

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A phase II, single arm study investigating neoadjuvant plus adjuvant treatment with Cemiplimab in high risk, surgically resectable, stage III Cutaneaous Squamous Cell Carcinoma

Studio di fase II, a singolo braccio su trattamento neo-adiuvante più adiuvante con cemiplimab nel carcinoma cutaneo a cellule squamose di stadio III, ad alto rischio, resecabile chirurgicamente

A.3.2

Name or abbreviated title of the trial where available

NEO-CESQ

A.4.1

Sponsor's protocol code number

NEO-CESQ

A.5.4

Other Identifiers

Name:

NEO-CESQ

Number:

NEO-CESQ

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	FONDAZIONE MELANOMA ONLUS
B.1.3.4	Country	Italy
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Sanofi Italia
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Clinical Research Technology Srl
B.5.2	Functional name of contact point	Clinical Operations
B.5.3	Address:
B.5.3.1	Street Address	Via San Leonardo Traversa Migliaro
B.5.3.2	Town/ city	Salerno
B.5.3.3	Post code	84131
B.5.3.4	Country	Italy
B.5.4	Telephone number	+39089301545
B.5.5	Fax number	+390897724155
B.5.6	E-mail	neo-cesq@cr-technology.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	LIBTAYO
D.2.1.1.2	Name of the Marketing Authorisation holder	REGENERON IRELAND DESIGNATED ACTIVITY COMPANY (DAC)
D.2.1.2	Country which granted the Marketing Authorisation	Italy
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	cemiplimab
D.3.2	Product code	[REGN2810]
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	FRAMMENTI MONOVALENTI E BIVALENTI DELL'ANTICORPO MONOCLONALE MURINO (Mab)
D.3.9.1	CAS number	1801342-60-8
D.3.9.2	Current sponsor code	Libtayo
D.3.9.3	Other descriptive name	anti-PD-1 mAb
D.3.9.4	EV Substance Code	SUB179369
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

high risk, surgically resectable, stage III Cutaneous Squamous Cell Carcinoma

carcinoma cutaneo a cellule squamose di stadio III, ad alto rischio, resecabile chirurgicamente

E.1.1.1

Medical condition in easily understood language

high risk, surgically resectable, stage III Cutaneous Squamous Cell Carcinoma

carcinoma cutaneo a cellule squamose di stadio III, ad alto rischio, resecabile chirurgicamente

E.1.1.2

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10041834
E.1.2	Term	Squamous cell carcinoma of skin
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Major pathological response rate (i.e., <10% remaining viable tumour cells in resected primary tumor).

Tasso di risposta patologica maggiore (ovvero <10% delle cellule tumorali vitali rimanenti nel tumore primario resecato).

E.2.2

Secondary objectives of the trial

• Recurrence-free survival (RFS - the time from start of treatment until disease recurrence (local, regional or distant) or death from any cause)
• Overall Survival (OS - the time from the date of first dose until the date of death from any cause.)
• Safety
• To determine molecular and immunophenotypic changes in tumor and peripheral blood evaluating several biomarkers. Since the identification of new markers for immunotherapy is rapidly evolving, the definitive list of analyses remains to be determined; however, the following tests are planned (differences between baseline and surgical time points and at recurrence, will be compared)

• Sopravvivenza libera da recidiva (RFS: tempo dalla randomizzazione all’evento recidiva -sviluppo di malattia a livello locale o distante -o morte per qualsiasi causa)
• Sopravvivenza globale (OS: il tempo dalla data della prima dose fino alla data del decesso per qualsiasi causa.)
• Sicurezza
• Determinare i cambiamenti molecolari e immunofenotipici nel tumore e nel sangue periferico valutando diversi biomarcatori. Dal momento che l'identificazione di nuovi marcatori per l'immunoterapia sono in rapida evoluzione, resta da stabilire l'elenco definitivo delle analisi; tuttavia, sono previsti i seguenti test (verranno confrontate le differenze tra i punti temporali di base e quelli chirurgici e al momento della ricorrenza)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1) Patients of either sex aged =18 years.
2) Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
3) Patients must have histologically or cytologically locally advanced cutaneous squamous cell carcinomas. The definition of resectability can be determined by the patient's surgical oncologist and verified via discussion at Multidisciplinary Tumor Conference attended by CSCC medical and surgical oncology staff. Resectable tumors are defined as having no significant vascular, neural or bony involvement.
4) Patients must be medically fit enough to undergo surgery as determined by the surgical oncology team.
5) Patients must have measurable disease, defined by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.
6) Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
7) Patients must have organ and marrow function as defined below: absolute neutrophil count (ANC) =1.5 X 10^9/L; hemoglobin =9.5 g/dL; platelets =100 X 10^9/L; prothrombin time/international normalized ratio (PT/INR) and partial thromboplastin time (PTT) =1.5 X upper limit of normal (ULN); total bilirubin =1.5 X ULN (isolated bilirubin >1.5 X ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =2.5 X ULN ^1; albumin =2.5 g/dL; creatinine =1.5 X ULN 2 OR calculated creatinine clearance =50 mL/min OR 24-hour urine creatinine clearance =50 mL/min.
8) Female subjects of childbearing potential must have a negative pregnancy test result at baseline and must practice a reliable method of contraception for the total study duration plus 16 weeks (i.e., 30 days plus the time required for cemiplimab to undergo five half-lives) after the last dose of cemiplimab.
9) Men who are sexually active with women of childbearing potential must practice a reliable method of contraception for the total study duration plus 16 weeks (i.e., 80 days plus the time required for cemiplimabto undergo five half-lives) after the last dose of cemiplimab.

1) Pazienti di entrambi i sessi di età =18 anni.
2) In grado di fornire un consenso informato scritto, che include la conformità ai requisiti e alle restrizioni elencati nel modulo di consenso.
3) I pazienti devono presentare carcinomi cutanei squamosi istologicamente o citologicamente localmente avanzati. La definizione di resecabilità può essere determinata dall'oncologo chirurgico del paziente e verificata attraverso la discussione alla Conferenza multidisciplinare sui tumori alla quale partecipano CSCC Medical e personale di oncologia chirurgica. I tumori resecabili sono definiti come privi di un significativo coinvolgimento vascolare, neurale o osseo.
4) I pazienti devono essere sufficientemente idonei dal punto di vista medico per sottoporsi a un intervento chirurgico come determinato dal team di oncologia chirurgica.
5) I pazienti devono avere una malattia misurabile, definita dai criteri di valutazione della risposta nei tumori solidi (RECIST) 1.1.
6) Stato delle prestazioni del Cooperative Oncology Group (ECOG) orientale 0-1.
7) I pazienti devono avere la funzione di organo e midollo come definita di seguito: conta assoluta dei neutrofili (ANC) = 1,5 X 10^9/L; emoglobina =9,5 g / dL; piastrine =100 X 10 ^ 9 / L; tempo di protrombina / rapporto internazionale normalizzato (PT / INR) e tempo di tromboplastina parziale (PTT) = 1,5 X limite superiore della norma (ULN); bilirubina totale = 1,5 X ULN (la bilirubina isolata> 1,5 X ULN è accettabile se la bilirubina è frazionata e la bilirubina diretta <35%); aspartato aminotransferasi (AST) e alanina aminotransferasi (ALT) =2,5 X ULN ^ 1; albumina =2,5 g / dL; creatinina = 1,5 X ULN 2 o clearance della creatinina calcolata =50 mL/min o clearance della creatinina delle urine nelle 24 ore =50 mL/min.
8) Le donne in età fertile devono avere un risultato del test di gravidanza negativo al basale e devono praticare un metodo contraccettivo affidabile per la durata totale dello studio più 16 settimane (ovvero, 30 giorni più il tempo necessario affinché cemiplimab subisca cinque emivite) dopo l'ultima dose di cemiplimab.
9) Gli uomini che sono sessualmente attivi con donne in età fertile devono praticare un metodo contraccettivo affidabile per la durata totale dello studio più 16 settimane (ovvero 80 giorni più il tempo necessario per cemiplimab per sottoporsi a 5 emivite) dopo l'ultima dose di cemiplimab .

E.4

Principal exclusion criteria

1) Evidence of metastatic disease extra lymphnodal.
2) Currently and previous cancer therapy (chemotherapy, radiation therapy, immunotherapy, or biologic therapy) or investigational anti-cancer drug.
3) Prior malignancy within the prior 5 years, except for the following: in-situ cervical cancer, thyroid cancer (except anaplastic) or any cancer from which the patient has been disease-free for 2 years.
4) Any major surgery within the last 3 weeks.
5) Unwillingness or inability to follow the procedures required in the protocol.
6) Uncontrolled diabetes, hypertension, pneumonitis and abnormal thyroid function or other medical conditions that may interfere with assessment of toxicity.
7) Subjects with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of treatment.
8) Female subjects who are pregnant (positive pregnancy test), breast-feeding, or who are of childbearing potential and not practicing a reliable method of birth control.
9) Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection;
10) Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).

1) Evidenza di malattia metastatica extra linfonodale.
2) Terapia del cancro attuale e precedente (chemioterapia, radioterapia, immunoterapia o terapia biologica) o farmaco antitumorale sperimentale.
3) Neoplasie pregresse nei 5 anni precedenti, ad eccezione di quanto segue: carcinoma cervicale in situ, carcinoma tiroideo (tranne anaplastico) o qualsiasi tumore da cui il paziente sia stato libero da malattia per 2 anni.
4) Qualsiasi intervento chirurgico importante nelle ultime 3 settimane.
5) Riluttanza o incapacità di seguire le procedure richieste nel protocollo.
6) Diabete non controllato, ipertensione, polmonite e funzionalità tiroidea anormale o altre condizioni mediche che possono interferire con la valutazione della tossicità.
7) Soggetti con una condizione che richiede un trattamento sistemico con corticosteroidi (> 10 mg equivalenti al prednisone al giorno) o altri farmaci immunosoppressori entro 14 giorni dal trattamento.
8) Donne in gravidanza (test di gravidanza positivo), in allattamento o in età fertile che non praticano un metodo affidabile di controllo delle nascite.
9) Test positivo per l'antigene di superficie del virus dell'epatite B (HBV sAg) o l'acido ribonucleico del virus dell'epatite C (anticorpo HCV) che indica un'infezione acuta o cronica;
10) Storia nota di test positivi per virus dell'immunodeficienza umana (HIV) o sindrome da immunodeficienza acquisita nota (AIDS).

E.5 End points

E.5.1

Primary end point(s)

the major pathological response rate

Tasso di risposta patologica maggiore

E.5.1.1

Timepoint(s) of evaluation of this end point

43-71 days

43-71 giorni

E.5.2

Secondary end point(s)

Recurrence-free survival; Overall Survival; Safety; To determine molecular and immunophenotypic changes in tumor and peripheral blood evaluating several biomarkers. Since the identification of new markers for immunotherapy is rapidly evolving, the definitive list of analyses remains to be determined.

Recurrence-free survival; Overall Survival; Safety; Determinare i cambiamenti molecolari e immunofenotipici nel tumore e nel sangue periferico per alcuni biomarkers. Poiché l'identificazione di nuovi marcatori per
l'immunoterapia è in rapida evoluzione, resta da stabilire l'elenco definitivo delle analisi.

E.5.2.1

Timepoint(s) of evaluation of this end point

at disease recurrence or death from any cause; Until three years from last infusion; countinuosly during the study; screening and at recurrence of disease

alla ricorrenza della malattia o morte per qualsiasi causa; Fino a tre anni dall'ultima infuzione; in modo continuativo durante lo studio; screening e alla ricorrenza di malattia

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS: All patients will be followed for survival and new anti-cancer therapy information untill 3 years from last treatment received

LVLS: tutti i pazienti saranno seguiti per la sopravvivenza e informazioni su nuovi trattamenti sperimentali fino a 3 anni dall'ultimo trattamento ricevuto

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Subject incapable of giving consent for physical reasons or reason linked to their medical condition

Soggetto incapace di dare il consenso per motivi fisici o motivi legati alla loro condizione medica

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

2 safety follow-up 28 and 84 days from last infusion and Every 3 months up to 3 years from last infusion

due visite di safety follow-up a 28 e 84 giorni dall'ultima infusione e una visita ogni tre mesi per tre anni dall'ultima infusione

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2020-10-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-07-29

P. End of Trial
P.	End of Trial Status	Ongoing

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