Clinical Trials Register

Summary
EudraCT Number:	2022-001144-18
Sponsor's Protocol Code Number:	MS202359_0002
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:	2022-07-21
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

2022-001144-18

A.3

Full title of the trial

A randomized, double-blind, placebo-controlled, 2-arm Phase III study to
assess efficacy and safety of xevinapant and radiotherapy compared to
placebo and radiotherapy for demonstrating improvement of disease-free
survival in participants with resected squamous cell carcinoma of the head
and neck, who are at high risk for relapse and are ineligible for high-dose
cisplatin

Studio di fase III, randomizzato, in doppio cieco, controllato con placebo, a 2 bracci, per valutare l’efficacia e la sicurezza di xevinapant e radioterapia rispetto a placebo e radioterapia, al fine di comprovare il miglioramento della sopravvivenza libera da malattia in partecipanti con carcinoma resecato a cellule squamose di testa e collo, ad alto rischio di recidiva e non idonei al cisplatino ad alto dosaggio

A.3.1

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

A clinical study comparing efficacy and safety of xevinapant against
placebo when given with radiotherapy in participants who had their locally
advanced squamous cell carcinoma of the head and neck removed by
surgery, are at high risk for the cancer to return and who cannot be treated
with high-dose cisplatin.

Studio clinico atto a comparare l'efficacia e la sicurezza di xevinapant rispetto al placebo in pazienti in radioterapia e operati chirurgicamente per carcinoma a cellule squamose di testa e collo, ad alto rischio recidiva e non idonei al cisplatino ad alto dosaggio.

A.3.2

Name or abbreviated title of the trial where available

Phase III xevinapant and radiotherapy in resected LA SCCHN

Fase III xevinapant e radioterapia in LA SCCHN resecato

A.4.1

Sponsor's protocol code number

MS202359_0002

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	MERCK HEALTHCARE KGaA
B.1.3.4	Country	Germany
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Merck Healthcare KGaA
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Merck Healthcare KGaA
B.5.2	Functional name of contact point	Communication Centre
B.5.3	Address:
B.5.3.1	Street Address	Frankfurter Str. 250
B.5.3.2	Town/ city	Darmstadt
B.5.3.3	Post code	64293
B.5.3.4	Country	Germany
B.5.4	Telephone number	+496151725200
B.5.5	Fax number	+496151725200
B.5.6	E-mail	service@merckgroup.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	No
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	Xevinapant
D.3.2	Product code	[MSC2735845A]
D.3.4	Pharmaceutical form	Oral solution
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	MSC2735845A
D.3.9.3	Other descriptive name	Xevinapant
D.3.9.4	EV Substance Code	SUB189921
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	20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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	No
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Oral solution
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Resected squamous cell carcinoma of the head and neck

Carcinoma a cellule squamose resecato della testa e del collo

E.1.1.1

Medical condition in easily understood language

Resected squamous cell carcinoma of the head and neck

Carcinoma a cellule squamose resecato della testa e del collo

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
E.1.2	Level	PT
E.1.2	Classification code	10060121
E.1.2	Term	Squamous cell carcinoma of head and neck
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

The purpose of this study is to demonstrate improvement in Disease-
Free Survival (DFS) with xevinapant compared to placebo when added to
RT irrespective of subsequent anticancer therapy.

Lo scopo di questo studio è dimostrare il miglioramento della Sopravvivenza libera da malattia
(DFS) con xevinapant rispetto al placebo quando aggiunto alla
RT indipendentemente dalla successiva terapia antitumorale.

E.2.2

Secondary objectives of the trial

- To demonstrate improvement in OS with xevinapant compared to
placebo when added to RT followed by subsequent anticancer therapy
- To evaluate time to subsequent cancer treatments in participants
treated with xevinapant compared to placebo when added to RT
- To evaluate the safety and tolerability of xevinapant compared to
placebo when added to RT
- To evaluate xevinapant compared to placebo when added to RT
followed by xevinapant monotherapy in terms of patient-reported head
and neck pain, swallowing, and speech as measured by the EORTC
H&N35 sub scales, patient-reported fatigue, physical function, and global
health status as measured by the EORTC QLQ C-30 sub scales and EQ-
5D-5L VAS

- Dimostrare il miglioramento dell'overall survival con xevinapant rispetto a
placebo quando aggiunto a RT seguito da successiva terapia antitumorale
- Valutare le tempistiche dei successivi trattamenti contro il cancro nei partecipanti
trattati con xevinapant rispetto al placebo quando aggiunto a RT
- Valutare la sicurezza e la tollerabilità di xevinapant rispetto a
placebo quando aggiunto a RT
- Valutare xevinapant rispetto al placebo quando aggiunto a RT
seguita da xevinapant in monoterapia in termini di dolori a collo e testa riferiti dal paziente, deglutizione e linguaggio misurati dall'EORTC
Sottoscale H&N35, affaticamento riportato dal paziente, funzione fisica e globale
stato di salute misurato tramite EORTC QLQ C-30 e EQ-
5D-5L VAS

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Participants with Eastern Cooperative Oncology Group Performance
Status (ECOG PS) 0-1
• Participants with histologically confirmed squamous cell carcinoma
with one of the following primary sites: oral cavity, oropharynx,
hypopharynx or larynx. Participants have received surgery with curative
intent on these sites in the past 4 to 8 weeks before start of treatment
(Cycle 1 Day 1)
• Oropharynx (OPC) participants must have known human
papillomavirus (HPV) status as determined by p16 expression using
immunohistochemistry ICH)
• Participants with no residual disease by computed tomography (CT)
and 2-deoxy-2-[fluorine-18] fluoro-D-glucose positron emission
tomography (18F-FDG-PET) and have a high risk of relapse with 1 or 2 of
the following criteria, confirmed by local histopathology:
• nodal extra-capsular extension (ECE) and positive resection margins
(R1 or close margin less than or equal to (<=) 1 millimeter (mm)
• Are unfit to receive high-dose cisplatin by meeting one or more of the
following criteria: 30 < estimated glomerular filtration rate (eGFR) < 60
milliliter per minute per 1.73 meter square (mL/min /1.73 m^2);
History of hearing loss, defined as Grade >= 2 audiometric hearing loss.
An
audiogram is not required if one of the other criteria meets unfitness to
receive high-dose cisplatin; Peripheral neuropathy > = Grade 2 and if >=
70 years, unfit according to G8 questionnaire (Score <= 14)
• Participants with adequate hematologic and hepatic function as
defined in the protocol
• Other protocol-defined inclusion criteria could apply

• Partecipanti con Eastern Cooperative Oncology Group Performance
Status (ECOG PS) 0-1
• Partecipanti con carcinoma a cellule squamose istologicamente confermato
con una delle seguenti sedi primarie: cavità orale, orofaringe,
ipofaringe o laringe. I partecipanti hanno ricevuto un intervento chirurgico con curativo
intento su questi siti nelle ultime 4-8 settimane prima dell'inizio del trattamento
(Ciclo 1 Giorno 1)
• I partecipanti all'orofaringe (OPC) devono essere a conoscenza dello
stato relativo al papillomavirus (HPV) determinato dall'espressione di p16 tramite
immunoistochimica ICH)
• Partecipanti senza malattia residua accertata mediante tomografia computerizzata (TC)
e18F-FDG-PET e con alto rischio di recidiva con 1 o 2 di
i seguenti criteri, confermati dall'istopatologia locale:
• estensione extracapsulare nodale (ECE) e margini di resezione positivi
(R1 o margine chiuso minore o uguale a (<=) 1 millimetro (mm)
• Non sono idonei a ricevere cisplatino ad alte dosi incontrando uno o più dei
seguenti criteri: 30 < velocità di filtrazione glomerulare stimata (eGFR) < 60
millilitri al minuto per 1,73 metri quadrati (mL/min /1,73 m^2);
Storia di perdita dell'udito, definita come perdita dell'udito audiometrica di Grado >= 2.

L'audiogramma non è richiesto se uno degli altri criteri soddisfa l'impossiblità nel
ricevere cisplatino ad alte dosi; Neuropatia periferica > = Grado 2 e se >=
70 anni, non idoneo secondo il questionario G8 (Punteggio <= 14)
• Partecipanti con adeguata funzionalità ematologica ed epatica come
definito nel protocollo
• Potrebbero essere applicati altri criteri di inclusione definiti dal protocollo

E.4

Principal exclusion criteria

• Any condition, including any uncontrolled disease state other than
SCCHN that in the Investigator's opinion constitutes an inappropriate
risk or a contraindication for participation in the study or that could
interfere with the study objectives, conduct, or evaluation
• Participant with incomplete surgery
• Primary tumor of nasopharyngeal, paranasal sinuses, nasal cavity,
salivary, thyroid or parathyroid gland, skin or unknown primary site
• Prior definitive, neoadjuvant, concurrent or adjuvant (C)RT to the head
and neck region which may jeopardize the primary tumor irradiation
plan,or any other prior SCCHN systemic treatment, including
investigational agents
• Participation in any clinical study within 28 days prior to screening or
during participation in this study
• Known contraindication to undergoing positron emission tomography
with 18F-FDG-PET-CT scans, or both contrast-enhanced MRI and
contrast enhanced CT scans
• Known allergy to Xevinapant (Debio 1143) or any excipient known to
be present in Xevinapant (Debio 1143) or in the placebo formulation
• Other protocol-defined exclusion criteria could apply

• Qualsiasi condizione, incluso qualsiasi stato patologico non controllato diverso da
SCCHN che a giudizio del PI costituisce un rischio inappropriato
una controindicazione alla partecipazione allo studio o che potrebbe
interferire con gli obiettivi, la condotta o la valutazione dello studio
• Partecipante con chirurgia incompleta
• Tumore primitivo del nasofaringe, dei seni paranasali, della cavità nasale,
ghiandola salivare, tiroidea o paratiroidea, cute o sede primaria sconosciuta
• Precedente (C)RT definitiva, neoadiuvante, concomitante o adiuvante alla testa
e regione del collo che possono compromettere l'irradiazione del tumore primario
piano o qualsiasi altro trattamento sistemico SCCHN precedente, incluso
agenti investigativi
• Partecipazione a qualsiasi studio clinico entro 28 giorni prima dello screening o
durante la partecipazione a questo studio
• Controindicazione nota alla tomografia a emissione di positroni
con scansioni 18F-FDG-PET-CT, o entrambe le risonanze magnetiche con mezzo di contrasto e
scansioni TC con contrasto migliorato
• Allergia nota a Xevinapant (Debio 1143) oa qualsiasi eccipiente noto
essere presente in Xevinapant (Debio 1143) o nella formulazione placebo
• Potrebbero essere applicati altri criteri di esclusione definiti dal protocollo

E.5 End points

E.5.1

Primary end point(s)

Disease-Free Survival (DFS)

Sopravvivenza libera da malattia

E.5.1.1

Timepoint(s) of evaluation of this end point

Time from randomization to the first occurrence of death from any cause
or objective disease recurrence,
assessed up to 5 years

Tempo dalla randomizzazione alla prima occorrenza di morte per qualsiasi causa
o oggettivamente riconducibile alla malattia, valutato fino a 5 anni

E.5.2

Secondary end point(s)

1. Overall Survival (OS)
2. Time to Subsequent Cancer Treatments
3. Number of Participants with Adverse Events (AEs) and Treatmentrelated
AEs
4. Change from Baseline in European Organization for Research and
Treatment of Cancer Quality of Life Head and Neck Module (EORTC QLQHN35)
Score
5. Change from Baseline in European Organization for research and
Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQC30)
Score
6. Change from Baseline in EuroQOL 5 Dimension 5 Level Health-Related
Quality of Life Measure Visual Analog Scale Score (EQ-5D-5L VAS)

1. Sopravvivenza globale (OS)
2. Tempo per i successivi trattamenti contro il cancro
3. Numero di partecipanti con eventi avversi (EA) e correlati al trattamento
AE
4. Modifiche rispetto alla baseline della European Organization for Research e dello score del
Treatment of Cancer Quality of Life Head and Neck Module (EORTC QLQHN35)
5. Modifiche rispetto alla baseline della European Organization for Research e dello score del
Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQC30)
Score
6. Cambiamento rispetto alla baseline in EuroQOL 5 Dimension 5 Level Health-Related
Quality of Life Measure Visual Analog Scale Score (EQ-5D-5L VAS)

E.5.2.1

Timepoint(s) of evaluation of this end point

1. Time from randomization to death from any cause, assessed up to 5
years
2. Time from randomization to the start of first subsequent cancer
treatment, assessed up to 5 years
3. Time from randomization until end of study (up to 5 years)
4. Baseline up to follow-up (5 years)
5. Baseline up to follow-up (5 years)
6. Baseline up to follow-up (5 years)

1. Tempo dalla randomizzazione al decesso per qualsiasi causa, valutato fino a 5
anni
2. Tempo dalla randomizzazione all'inizio del primo tumore successivo
trattamento, valutato fino a 5 anni
3. Tempo dalla randomizzazione fino alla fine dello studio (fino a 5 anni)
4. Baseline fino al follow-up (5 anni)
5. Baseline fino al follow-up (5 anni)
6. Baseline fino al follow-up (5 anni)

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

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

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

Yes

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

110

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Argentina

Australia

Brazil

Canada

China

India

Israel

Japan

Korea, Republic of

Mexico

Taiwan

United States

Austria

Finland

France

Poland

Sweden

Netherlands

Romania

Spain

Switzerland

Czechia

Germany

Greece

Italy

Belgium

Denmark

Georgia

Hungary

Ireland

Norway

Portugal

Turkey

United Kingdom

E.8.7

Trial has a data monitoring committee

Yes

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

Last Patient Last Visit

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:

315

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

385

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

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

314

F.4.2.2

In the whole clinical trial

700

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)

Participants will be receiving the appropriate follow-up treatment per
institutional standards.

I partecipanti riceveranno il trattamento di follow-up appropriato per
standard istituzionali

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

2022-09-29

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-09-07

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

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