Clinical Trials Register

Summary
EudraCT Number:	2019-004770-25
Sponsor's Protocol Code Number:	D7310C00001
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:	2021-01-21
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

2019-004770-25

A.3

Full title of the trial

A Phase 3 Randomized, Double-blind, Multicenter, Global Study of Monalizumab or Placebo in Combination with Cetuximab in Patients with Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
Previously Treated With an Immune Checkpoint Inhibitor (INTERLINK-1).

Studio globale di fase 3 randomizzato, in doppio cieco, multicentrico, di Monalizumab o placebo in combinazione con Cetuximab in pazienti affetti da carcinoma a cellule squamose della testa e del collo, ricorrente o metastatico, precedentemente trattati con un inibitore dei checkpoint immunitari (INTERLINK-1).

A.3.1

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

Study of Monalizumab Given With Cetuximab or Placebo Given with Cetuximab in Patients With Head and Neck Cancer that has come back or spread to other parts of the body.

Studio di Monalizumab somministrato con Cetuximab o Placebo somministrato con Cetuximab in pazienti con tumore della testa e del collo ricorrente o che si è diffuso ad altre parti del corpo.

A.3.2

Name or abbreviated title of the trial where available

INTERLINK-1

A.4.1

Sponsor's protocol code number

D7310C00001

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	ASTRAZENECA AB
B.1.3.4	Country	Sweden
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	AstraZeneca AB
B.4.2	Country	Sweden
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	AstraZeneca AB
B.5.2	Functional name of contact point	Clinical Trial Transparency
B.5.3	Address:
B.5.3.1	Street Address	Karlebyhus, Astraallén
B.5.3.2	Town/ city	Södertälje
B.5.3.3	Post code	SE 151 85
B.5.3.4	Country	Sweden
B.5.6	E-mail	ClinicalTrialTransparency@astrazeneca.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Comparator
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	Cetuximab
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Europe B.V.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Cetuximab
D.3.2	Product code	[NA]
D.3.4	Pharmaceutical form	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	CETUXIMAB
D.3.9.1	CAS number	205923-56-4
D.3.9.2	Current sponsor code	NA
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	5
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.IMP: 2
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	Monalizumab
D.3.2	Product code	[IPH2201]
D.3.4	Pharmaceutical form	Powder and solvent 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	(1s, 4s)-4-(3,4-dichlorophenyl)-4-[(dimethylamino)methyl]-1-methylcyclohexanol maleate
D.3.9.1	CAS number	1228763-95-8
D.3.9.2	Current sponsor code	IPH2201
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.IMP: 3
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	Cetuximab
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Europe B.V.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Cetuximab
D.3.2	Product code	[NA]
D.3.4	Pharmaceutical form	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	CETUXIMAB
D.3.9.1	CAS number	205923-56-4
D.3.9.2	Current sponsor code	NA
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	5
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck Previously Treated With an Immune Checkpoint Inhibitor.

Pazienti con carcinoma a cellule squamose ricorrente o metastatico della testa e del collo precedentemente trattati con un inibitore del checkpoint immunitario.

E.1.1.1

Medical condition in easily understood language

Patients who had received prior immunotherapy treatment for specific type of head and neck cancer that has come back or spread to other parts of the body.

Pazienti che hanno ricevuto un precedente trattamento immunoterapico per un tipo specifico di tumore della testa e del collo ricorrente o che si è diffuso ad altre parti del corpo.

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	21.1
E.1.2	Level	PT
E.1.2	Classification code	10067821
E.1.2	Term	Head and neck cancer
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

To compare the effect of monalizumab and cetuximab (Arm A) relative to placebo and cetuximab (Arm B) in terms of overall survival (OS).

Confrontare l'effetto di monalizumab e cetuximab (braccio A) rispetto al placebo e cetuximab (braccio B) in termini di sopravvivenza globale (OS).

E.2.2

Secondary objectives of the trial

To compare the effect of monalizumab and cetuximab (arm A) relative to placebo and cetuximab (arm B) by:
1. assessment of PFS, ORR, DoR;
2. assessment of disease-related symptoms, functioning and quality of life;
3. characterization of the association between clinical outcome and protein expression in the tumor;
4. assessment of safety and tolerability.

To investigate PK and immunogenicity of monalizumab.

Confrontare l'effetto di monalizumab e cetuximab (braccio A) rispetto a placebo e cetuximab (braccio B) di:
1. valutazione di PFS, ORR, DoR;
2. valutazione dei sintomi correlati alla malattia, funzionamento e qualità della vita;
3. caratterizzazione dell'associazione tra esito clinico ed espressione proteica nel tumore;
4. valutazione di sicurezza e tollerabilità.

Per studiare la PK e l'immunogenicità di monalizumab.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Are aged 18 years and over
2. Recurrent or metastatic SCCHN (oral cavity, oropharynx, hypopharynx, or larynx)
3. Received treatment using a PD-(L)1 inhibitor
4. Prior platinum failure
5. Received 1 or 2 prior systemic regimens for recurrent or metastatic SCCHN
6. At least one measurable lesion at baseline that qualifies RECIST 1.1
7. A fresh or recently acquired tumor tissue for the purpose of biomarker testing
8. WHO/ECOG PS of 0 or 1

Pazienti:
1. con erà maggiore o uguale a 18 anni
2. con SCCHN ricorrente o metastatico (cavità orale, orofaringe, ipofaringe o laringe)
3. che hanno ricevuto il trattamento utilizzando un inibitore PD- (L) 1
4. con precedente fallimento del trattamento con platino
5. che hanno ricevuto 1 o 2 precedenti regimi sistemici per SCCHN ricorrente o metastatico
6. con almeno una lesione misurabile al basale che qualifica RECIST 1.1
7. con campione di tessuto tumorale fresco o acquisito di recente ai fini di test sui biomarcatori
8. con WHO/ECOG PS pari a 0 o 1

E.4

Principal exclusion criteria

1. Head and neck cancer of any primary anatomic location in the head and neck not specified in the inclusion criteria, including participants with SCCHN of unknown primary or non-squamous histologies
2. Had prior cetuximab therapy (unless it was administered in curative LA setting with radiotherapy and no disease progression for at least 6 months following the last cetuximab dose)
3. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn's disease], diverticulitis
4. Any concurrent anticancer treatment, except for hormonal therapy for non-cancer-related conditions (eg, hormone replacement therapy)

Pazienti:
1. Con carcinoma testa collo in qualsiasi posizione anatomica primaria nella testa e nel collo non specificata nei criteri di inclusione, inclusi i partecipanti con SCCHN ad istologie primarie o non squamose sconosciute
2. Che hanno ricevuto una terapia precedente con cetuximab (a meno che non sia stato somministrato in setting curativo LA con radioterapia e senza progressione della malattia per almeno 6 mesi dopo l'ultima dose di cetuximab)
3. Con disturbi autoimmuni o infiammatori attivi o precedentemente documentati (inclusa la malattia infiammatoria intestinale [p. Es., Colite o morbo di Crohn], diverticolite)
4. che ricevono qualsiasi trattamento antitumorale concomitante, ad eccezione della terapia ormonale per condizioni non correlate al cancro (ad es. Terapia ormonale sostitutiva)

E.5 End points

E.5.1

Primary end point(s)

Overall survival, defined as the time from the date of randomization until date of death due to any cause.

Sopravvivenza globale, definita come il periodo di tempo dalla data della randomizzazione fino alla data del decesso per qualsiasi causa.

E.5.1.1

Timepoint(s) of evaluation of this end point

Assessments of survival status must be made periodically from enrollment.

Le valutazioni dello stato di sopravvivenza devono essere effettuate periodicamente dall'arruolamento.

E.5.2

Secondary end point(s)

- PFS is defined as time from randomization until disease progression, per RECIST 1.1 as assessed by the investigator at local site or death due to any cause, whichever occurs first.
- ORR is defined as the proportion of participants with measurable disease who have a confirmed CR or PR, as determined by the investigator at local site per RECIST 1.1.
- DoR is defined as the time from the date of first documented response until date of documented disease progression or death in the absence of disease progression.
- Patient questionnaires regarding wellbeing and symptom change in baseline scores across visits
- Concentration of monalizumab in the blood
- Presence of antibodies to monalizumab in the blood
- Measurement of specific biomarkers in the tumor sample(s)
- AEs, vital signs, clinical laboratory results, ECGs

- La PFS è definita come il tempo che intercorre tra la randomizzazione e la progressione della malattia, secondo RECIST 1.1 come valutato dallo sperimentatore nel centro a livello locale o morte per qualsiasi causa, a seconda di quale evento si verifichi per primo.
- ORR è definito come la percentuale di partecipanti con malattia misurabile che hanno una CR o PR confermata, come determinato dallo sperimentatore nel centro a livello locale secondo RECIST 1.1.
- DoR è definito come il tempo che intercorre dalla data della prima risposta documentata fino alla data della progressione della malattia documentata o della morte in assenza di progressione della malattia.
- Questionari per i pazienti riguardanti il benessere e la variazione dei sintomi nei punteggi di base durante le visite
- Concentrazione di monalizumab nel sangue
- Presenza di anticorpi contro monalizumab nel sangue
- Misurazione di biomarcatori specifici nei campioni di tumore
- Eventi avversi, segni vitali, risultati di laboratorio clinici, ECG

E.5.2.1

Timepoint(s) of evaluation of this end point

Periodically from enrollment.

Periodicamente dall'arruolamento.

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

Yes

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

Yes

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

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

Australia

Brazil

Canada

Japan

Korea, Democratic People's Republic of

Peru

Philippines

Russian Federation

Taiwan

United States

Austria

Belgium

Bulgaria

France

Germany

Greece

Italy

Romania

Spain

Switzerland

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

LVLS

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:

400

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

200

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

Caregiver

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

256

F.4.2.2

In the whole clinical trial

600

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)

After end of treatment with study drug, patients may be managed according to local standard of care or may continue study treatment for as long as receiving benefit.

Dopo la fine del trattamento con il farmaco in studio, i pazienti possono essere gestiti secondo gli standard di cura locali o possono continuare il trattamento in studio fino a quando ricevono benefici.

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

2020-07-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-06-15

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

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