Clinical Trials Register

Summary
EudraCT Number:	2020-000612-30
Sponsor's Protocol Code Number:	D910MC00001
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2021-06-14
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

2020-000612-30

A.3

Full title of the trial

A Phase III, Randomized, Multicenter, Double-blind, Placebo-controlled Study of Durvalumab for the Treatment of Stage II-III NSCLC Patients with Minimal Residual Disease Following Surgery and Curative Intent Therapy (MERMAID-2)

Studio di Fase III, Randomizzato, Multicentrico, in Doppio Cieco, Controllato con Placebo di Durvalumab per il Trattamento di Pazienti Affetti da NSCLC allo stadio II-III con Malattia Minima Residua dopo Intervento Chirurgico e Terapia con Intento Curativo (MERMAID-2)

A.3.1

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

Phase III study to evaluate the efficacy and safety of durvalumab compared to placebo in patients with NSCLC who have minimal residual disease after surgery + / - additional therapy before or after surgery

Studio di fase III per valutare l'efficacia di durvalumab rispetto al placebo in pazienti con NSCLC che hanno malattia minima residua dopo l'intervento chirurgico + / - terapia aggiuntiva prima o dopo la chirurgia

A.3.2

Name or abbreviated title of the trial where available

MERMAID-2

A.4.1

Sponsor's protocol code number

D910MC00001

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	MedImmune
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	AstraZeneca
B.5.2	Functional name of contact point	Information Center
B.5.3	Address:
B.5.3.1	Street Address	-
B.5.3.2	Town/ city	Karlebyhus, Astraallén
B.5.3.3	Post code	151 85
B.5.3.4	Country	Sweden
B.5.6	E-mail	information.center@astrazeneca.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	durvalumab
D.3.2	Product code	[MEDI4736]
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	durvalumab
D.3.9.1	CAS number	1428935-60-7
D.3.9.2	Current sponsor code	MEDI4736
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: 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	Yes
D.2.1.1.1	Trade name	Inflectra 100 mg powder for concentrate for solution for infusion
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer Europe MA EEIG
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	infliximab
D.3.2	Product code	[-]
D.3.4	Pharmaceutical form	Powder for 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	INFLIXIMAB
D.3.9.2	Current sponsor code	-
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
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	Mycophenolate mofetil Sandoz 250 mg capsules, hard
D.2.1.1.2	Name of the Marketing Authorisation holder	Sandoz GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Poland
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	micofenolato mofetile
D.3.2	Product code	[-]
D.3.4	Pharmaceutical form	Capsule, hard
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.3.8	INN - Proposed INN	MICOFENOLATO MOFETILE
D.3.9.2	Current sponsor code	-
D.3.9.3	Other descriptive name	mycophenolate mofetil
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	250
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	Concentrate for 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

Completely resected stage II-III NSCLC

NSCLC in stadio II-III completamente resecato

E.1.1.1

Medical condition in easily understood language

Patients with NSCLC who have minimal residual disease after surgery + / - additional therapy before or after surgery

Pazienti con NSCLC che presentano malattia minima residua dopo l'intervento chirurgico + / - terapia aggiuntiva prima o dopo la chirurgia

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	10061873
E.1.2	Term	Non-small cell lung 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 assess the efficacy of durvalumab compared to placebo as measured by DFS (using Investigator assessment according to RECIST 1.1.) in the PD-L1 TC=1% analysis set

Valutare l'efficacia di durvalumab rispetto al placebo misurata in termini di DFS (mediante la valutazione dello Sperimentatore secondo i criteri RECIST 1.1) nel set di analisi PD-L1 TC=1%

E.2.2

Secondary objectives of the trial

1. To assess the efficacy of durvalumab compared to placebo as measured by DFS in all randomized patients (using investigator assessment according to RECIST 1.1);
2. To assess the efficacy of durvalumab compared to placebo as measured by DFS in the PD-L1 TC=1% analysis set and in all randomized patients (using BICR assessment according to RECIST 1.1);
3. To assess the efficacy of durvalumab compared to placebo on postrecurrence outcomes;
4. To assess the efficacy of durvalumab compared to placebo as measured by OS in the PD-L1 TC=1% analysis set and in all randomized patients;
5. To assess patient-reported symptoms, functioning, and HRQoL in patients treated with durvalumab compared to placebo;
6. To investigate the relationship between a patient's baseline PD-L1 TC expression and efficacy of study treatments.

1. Valutare l'efficacia di durvalumab rispetto al placebo misurata in termini di DFS in tutti i pazienti randomizzati (mediante la valutazione dello Sperimentatore secondo i criteri RECIST 1.1);
2. Valutare l'efficacia di durvalumab rispetto al placebo misurata in termini di DFS nel set di analisi PD-L1 TC=1% e in tutti i pazienti randomizzati (mediante la valutazione BICR secondo i criteri RECIST 1.1);
3. Valutare l'efficacia di durvalumab rispetto al placebo in base agli esiti post-recidiva;
4. Valutare l'efficacia di durvalumab rispetto al placebo misurata in termini di OS nel set di analisi PD-L1 TC=1% e in tutti i pazienti randomizzati;
5. Valutare i sintomi riportati dai pazienti, la funzionalità e l'HRQoL nei pazienti trattati con durvalumab rispetto al placebo;
6. Studiare la relazione tra l'espressione PD-L1 TC nei pazienti al baseline e l'efficacia dei trattamenti di studio.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Capable of giving signed informed consent, which includes a mandatory genetic informed consent and compliance with the requirements and restrictions listed in the informed consent forms (ICFs) and study protocol;
2. Age =18 years at the time of screening;
3. Diagnosis of histologically confirmed NSCLC (WHO 2015 classification) with resectable (stage II-III) disease;
4. Complete resection of the primary NSCLC.

1. In grado di fornire il proprio consenso informato, che include un consenso informato genetico obbligatorio e in conformità con i requisiti e le restrizioni elencate nel modulo di consenso informato e nel protocollo di studio;
2. Età =18 anni nel momento dello screening;
3. Diagnosi confermata istologicamente di NSCLC (classificazione WHO 2015) con malattia resecabile (stadio II-III);
4. Resezione completa dell'NSCLC primario.

E.4

Principal exclusion criteria

1. EGFR and/or ALK mutant as assessed either from the tumor biopsy taken prior to surgery or the resected tumor tissue. Testing must be performed using a well-validated, local regulatory approved test;
2. Require re-resection or are deemed to have unresectable NSCLC by a multidisciplinary evaluation that must include a thoracic surgeon who perform lung cancer surgery as a significant part of their practice;
3. History of allogeneic organ or bone marrow transplantation;
4. Non-leukocyte-depleted whole blood transfusion in 120 days of genetic sample collection.

1. Mutazioni di EGFR e/o ALK, valutate sulla biopsia tumorale prelevata prima dell'intervento chirurgico o dal tessuto tumorale resecato. La valutazione deve essere effettuata mediante test validati e approvati dalle norme locali;
2. Richiedono re-resezione o ritenuti avere un NSCLC non resecabile secondo una valutazione multidisciplinare che deve includere un chirurgo toracico che effettua interventi chirurgici sui tumori polmonari come parte preponderante della sua pratica clinica;
3. Anamnesi di organi allogenici o di trapianto di midollo osseo;
4. Trasfusioni di sangue intero non leucodepleto nei 120 giorni precedenti il prelievo dei campioni genetici.

E.5 End points

E.5.1

Primary end point(s)

DFS in PD-L1 TC=1% (using Investigator assessments according to RECIST 1.1)

DFS nel set PD-L1 TC=1% (mediante la valutazione dello Sperimentatore secondo i criteri RECIST 1.1)

E.5.1.1

Timepoint(s) of evaluation of this end point

Approximately 3 years

Circa 3 anni

E.5.2

Secondary end point(s)

1. DFS in FAS (using Investigator assessments according to RECIST 1.1)
2. DFS (using BICR assessments according to RECIST 1.1) in PD-L1 TC=1% and in FAS
3. PFS (using local standard practice)
4. Time to first subsequent therapy (TFST)
5. Time to second subsequent therapy (TSST)
6. OS in PD-L1 TC=1% and in FAS
7. Change from baseline and time to deterioration in EORTC QLQ-C30 and EORTC QLQ-LC13
8. IHC analysis of PD-L1 TC expression and spatial distribution within the tumor microenvironment relative to efficacy outcomes (ie, DFS, OS)

1. DFS nel FAS (mediante la valutazione dello Sperimentatore secondo i criteri RECIST 1.1)
2. DFS (mediante la valutazione BICR secondo i criteri RECIST 1.1) nei set PD-L1 TC=1% e FAS
3. PFS (mediante la pratica standard locale)
4. Tempo alla prima terapia successiva (TFST)
5. Tempo alla seconda terapia successiva (TSST)
6. OS nei set PD-L1 TC=1% e FAS
7. Differenze tra baseline e tempo di deterioramento nei questionari EORTC QLQ-30 e EORTC QLQ-LC13
8. Analisi IHC dell'espressione PD-L1 TC e della distribuzione spaziale all'interno del microambiente tumorale in relazione ai risultati di efficacia (DFS, OS)

E.5.2.1

Timepoint(s) of evaluation of this end point

Approximately 5 years

Circa 5 anni

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

Yes

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

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)

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

Hong Kong

India

Israel

Japan

Peru

Russian Federation

Taiwan

Turkey

United States

Vietnam

Belgium

Bulgaria

Denmark

France

Germany

Hungary

Italy

Netherlands

Romania

Spain

Sweden

Switzerland

Czechia

Argentina

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

The end of study is defined as the last expected visit/contact of the last subject undergoing the study.

La conclusione dello studio è definita dall'ultima attesa visita/contatto dell'ultimo soggetto partecipante.

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:

200

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

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

104

F.4.2.2

In the whole clinical trial

284

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)

None

Nessuno

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

2020-12-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-10-09

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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