Clinical Trials Register

Summary
EudraCT Number:	2018-002997-29
Sponsor's Protocol Code Number:	D9106C00001
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2020-02-28
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

Spain - AEMPS

A.2

EudraCT number

2018-002997-29

A.3

Full title of the trial

A Phase III, Double-blind, Placebo-controlled, Multi-center International Study of Neoadjuvant/adjuvant Durvalumab for the Treatment of Patients with Resectable Stages II and III Non-small Cell Lung Cancer (AEGEAN)

Ensayo fase III, doble ciego, controlado con placebo, Internacional y multicéntrico de tratamiento neoadyuvante/adyuvante de Durvalumab para el tratamiento de pacientes con cáncer de pulmón no microcítico resecable en estadios II y III (AEGEAN)

A.3.1

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

A Study of Neoadjuvant/adjuvant Durvalumab for the Treatment of Patients with Resectable Non-small Cell Lung Cancer

Ensayo de durvalumab neoadyuvante/adyuvante para el tratamiento de pacientes con cáncer de pulmón no microcítico resecable

A.3.2

Name or abbreviated title of the trial where available

AEGEAN

A.4.1

Sponsor's protocol code number

D9106C00001

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 Farmacéutica Spain, S.A.
B.5.2	Functional name of contact point	Unidad de Investigación Clínica
B.5.3	Address:
B.5.3.1	Street Address	C/ Serrano Galvache, 56; Parque Norte, Edificio Álamo
B.5.3.2	Town/ city	Madrid
B.5.3.3	Post code	28033
B.5.3.4	Country	Spain
B.5.4	Telephone number	900200444
B.5.6	E-mail	informacionEECC-Spain@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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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 resectable Non-small Cell Lung Cancer (Stage IIA to IIIB; either squamous or non-squamous)

Pacientes con cáncer de pulmón no microcítico (CPNM) resecable (estadio IIA a estadio IIIB; escamoso o no escamoso)

E.1.1.1

Medical condition in easily understood language

Patients with "non-small cell lung cancer" (NSCLC) at a specific stage (Stage IIA to IIIB)

Pacientes con cáncer de pulmón no microcítico (CPNM) en estadio específico (estadio IIA a estadio IIIB)

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 compare the efficacy of durvalumab + chemotherapy administered prior to surgery followed
by durvalumab post-surgery compared with placebo + chemotherapy administered prior to surgery
followed by placebo post-surgery in terms of EFS
To compare the activity of durvalumab + chemotherapy administered prior to surgery compared with placebo + chemotherapy administered
prior to surgery in terms of mPR

Comparar la eficacia de durvalumab + quimioterapia administrado antes de la intervención quirúrgica seguido de durvalumab después de la intervención en comparación con placebo + quimioterapia administrado antes de la intervención quirúrgica seguido de placebo después de la intervención en la Supervivencia Libre de Eventos (SLEp).
Comparar la actividad de durvalumab + quimioterapia administrado antes de la intervención quirúrgica en comparación con placebo + quimioterapia administrado antes de la intervención quirúrgica en la mayor Respuesta Patológica (mRP).

E.2.2

Secondary objectives of the trial

- To assess activity of durvalumab + chemo administered prior to surgery compared with placebo + chemo administered prior to surgery in terms of pCR
- To assess the efficacy of durvalumab + chemo administered prior to surgery followed by
durvalumab post-surgery compared with placebo + chemo administered prior to surgery followed by placebo post-surgery in terms of EFS, DFS, and OS
- To assess disease-related symptoms and Health-Related Quality of Life (HRQoL) in patients treated with durvalumab + chemo administered prior to surgery followed by durvalumab post-surgery compared with placebo + chemo administered prior to surgery followed by placebo post-surgery
- To assess the pharmacokinetics (PK) and immunogenicity of durvalumab

Evaluar la actividad de durvalumab+quimioterapia administrado antes de la intervención quirúrgica (i.q.) en comparación con placebo+quimioterapia administrado antes dela i.q. en la Respuesta Patológica completa (RPc).
Evaluar la eficacia de durvalumab+quimioterapia administrado antes de la i.q. seguido de durvalumab después de la intervención en comparación con placebo+quimioterapia administrado antes de la i.q. seguido de placebo después de la intervención en la SLEp, Supervivencia Libre de Enfermedad (SLE) y Supervivencia Global (SG).
Evaluar los síntomas relacionados con la enfermedad y la calidad de vida relacionada con la salud (CVRS) en pacientes tratados con durvalumab+quimioterapia administrado antes de la i.q. seguido de durvalumab después de la intervención en comparación con placebo+quimioterapia administrado antes de la i.q. seguido de placebo después de la intervención.
Evaluar la farmacocinética (FC) y la inmunogenicidad de durvalumab

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Age ≥18 years
2. Histologically or cytologically documented NSCLC with resectable (Stage IIA to select [ie, N2] Stage IIIB) disease
3. World Health Organization (WHO)/ECOG PS of 0 or 1 at enrollment
4. At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 Target Lesion (TL) at baseline
5. No prior exposure to immune-mediated therapy including, but not limited to, other anti-CTLA-4, anti-PD-1, anti-PD-L1, and anti-PD-L2 antibodies, excluding therapeutic anticancer vaccines.
6. Adequate organ and marrow function
7. Confirmation of a patients tumour PD-L1 status
8. Documented EGFR and ALK status

1. Edad ≥ 18 años
2. CPNM resecable (Estadio IIA (p.ej. N2) a Estadio IIIB ) documentado histológica o citológicamente.
3. Organización Mundial de la Salud (OMS)/ Eastern Cooperative Oncology Group (ECOG) de 0 o 1 en la inclusión
4. Al menos 1 lesión, no previamente irradiada, calificada como una Lesión Diana (LD) por criterio RECIST 1.1 en el momento basal
5. Sin exposición previa a terapia inmuno-mediada, incluyendo, entre otras, otros anticuerpos anti CTLA-4, anti-PD-1, anti-PD-L1, y anti-PD-L2, excluyendo terapias con vacunas anticancerígenas
6. Función adecuada de órganos y médula
7. Confirmación del estado PD-L1 del paciente
8. Estado de la mutación EGFR y ALK documentado

E.4

Principal exclusion criteria

1. History of allogeneic organ transplantation
2. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease, diverticulitis, systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome).
3. History of another primary malignancy
4. History of active primary immunodeficiency
5. Active infection including tuberculosis hepatitis B, or human immunodeficiency virus
6. Deemed unresectable NSCLC by multidisciplinary evaluation
7. Patients who have pre-operative radiotherapy treatment as part of their care plan
8. Patients who have brain metastases or spinal cord compression
9. Stage IIIB N3 and Stages IIIC, IVA, and IVB NSCLC
10. Mixed small cell and NSCLC histology
11. Patients who are candidates to undergo only segmentectomies or wedge resections

1. Antecedentes de trasplante alogénico de órganos.
2. Trastornos autoinmunes o inflamatorios activos o previamente documentados (incluyendo enfermedad inflamatoria intestinal, diverticulitis, lupus eritematoso sistémico, síndrome de sarcoidosis o síndrome de Wegener)
3. Antecedentes de otro cáncer primario
4. Antecedentes de inmunodeficiencia primaria activa
5. Infección activa incluyendo tuberculosis, hepatitis B o virus de inmunodeficiencia humana
6. Considerado CPNM irresecable por evaluación multidisciplinaria
7. Pacientes que reciben tratamiento preoperatorio con radioterapia como parte de su plan de atención
8. Pacientes con metástasis cerebrales o compresión de la médula espinal
9. CPNM Estadio IIIB N3 y Estadios IIIC, IVA, y IVB
10. Histología mixta de células pequeñas y CPNM
11. Pacientes que son candidatos a someterse solo a segmentectomías o resecciones en cuña

E.5 End points

E.5.1

Primary end point(s)

Event-free Survival (EFS) and Major Pathological Response (mPR) in full analysis set

Supervivencia libre de eventos (SLEp) y mayor respuesta patológica (mRP) en el grupo de análisis completo (GAC)

E.5.1.1

Timepoint(s) of evaluation of this end point

approximately 6 months after last patient randomized

Aproximadamente 6 meses después de la aleatorización del último paciente

E.5.2

Secondary end point(s)

1. pCR in FAS and PD-L1-TC positive patients
2. mPR in PD-L1-TC positive patients
3. EFS, DFS, OS
4. Change from baseline in Patient reported outcomes
5. Concentration of durvalumab
6. Presence of ADAs for durvalumab
7. EFS and DFS in PD-L1 TC positive patients

1. RPc en Grupo de Análisis Completo (GAC) y pacientes PD-L1-TC positivo
2. mRP en pacientes PD-L1-TC positivo
3. SLEp, SLE, SG
4. Cambio desde el momento basal en los resultados comunicados por los pacientes
5. Concentración de durvalumab
6. Presencia de Anticuerpos contra el fármaco (ACF) dirigidos contra durvalumab
7. SLEp y SLE en pacientes PD-L1-TC positivo

E.5.2.1

Timepoint(s) of evaluation of this end point

approximately 5.5 years after last patient has had surgery.

Aproximadamente 5,5 años después de la cirugía del último paciente

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

Yes

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

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

Austria

Belgium

Brazil

Bulgaria

Chile

China

Costa Rica

France

Germany

Hungary

India

Italy

Japan

Korea, Republic of

Mexico

Netherlands

Peru

Philippines

Poland

Romania

Russian Federation

Spain

Taiwan

Thailand

Ukraine

United States

Vietnam

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

LSLV

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:

280

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

520

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

238

F.4.2.2

In the whole clinical trial

800

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

Ninguno

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

2020-05-08

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-04-01

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

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