Clinical Trials Register

Summary
EudraCT Number:	2015-001279-39
Sponsor's Protocol Code Number:	D419AC00001
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2015-11-06
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

France - ANSM

A.2

EudraCT number

2015-001279-39

A.3

Full title of the trial

A Phase III Randomized, Open-Label, Multi-Center, Global Study of MEDI4736 in Combination with Tremelimumab Therapy or MEDI4736 Monotherapy Versus Standard of Care Platinum-Based Chemotherapy in First Line Treatment of Patients with Advanced or Metastatic Non Small-Cell Lung Cancer (NSCLC) (MYSTIC)

Étude internationale, multicentrique, de phase III, randomisée, en ouvert comparant le MEDI4736 en association au tremelimumab ou en monothérapie à une chimiothérapie conventionnelle à base de platine chez des patients atteints d’un cancer bronchique non à petites cellules (CBNPC) de stade avancé ou métastatique en première ligne de traitement (MYSTIC)

A.3.1

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

Study of MEDI4736 with or without Tremelimumab Versus standard of
care chemotherapy in lung cancer (MYSTIC Study)

Etude comparant le MEDI4736 avec ou sans Tremelimumab à une chimiothérapie conventionnelle dans le cancer du poumon (Etude MYSTIC)

A.3.2

Name or abbreviated title of the trial where available

MYSTIC

A.4.1

Sponsor's protocol code number

D419AC00001

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02453282

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	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	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	MEDI4736
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.3.9.3	Other descriptive name	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.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	Tremelimumab
D.3.2	Product code	MEDI1123
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	Tremelimumab
D.3.9.1	CAS number	745013-19-6
D.3.9.2	Current sponsor code	MEDI1123
D.3.9.3	Other descriptive name	MEDI1123
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	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.IMP: 3
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	Paclitaxel
D.2.1.1.2	Name of the Marketing Authorisation holder	Teva UK Limited
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Paclitaxel
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.3.11 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	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	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.IMP: 4
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	Carboplatin
D.2.1.1.2	Name of the Marketing Authorisation holder	Hospira UK Limited
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Carboplatin
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.3.11 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	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	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.IMP: 5
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	Gemcitabine
D.2.1.1.2	Name of the Marketing Authorisation holder	Activis Group PTC ehf.
D.2.1.2	Country which granted the Marketing Authorisation	Iceland
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	Gemcitabine
D.3.4	Pharmaceutical form	Powder for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.11 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	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	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.IMP: 6
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	Cisplatin
D.2.1.1.2	Name of the Marketing Authorisation holder	Hospira UK Limited
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Cisplatin
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.3.11 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	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	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.IMP: 7
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	Pemetrexed
D.2.1.1.2	Name of the Marketing Authorisation holder	Eli Lilly Nederland BV
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
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	Pemetrexed
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.3.11 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	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	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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Advanced or Metastatic Non Small-Cell Lung Cancer (NSCLC) in treatment naiive patients with epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) wild type tumour pathology.

Cancer bronchique non à petites cellules (CBNPC) de stade avancé ou métastatique en première ligne de traitement avec statut pour le récepteur de facteur de croissance épidermique (EGFR) et pour la kinase lymphome anaplasique (ALK) de type sauvage

E.1.1.1

Medical condition in easily understood language

Specific type of lung cancer called "non-small cell lung cancer" (NSCLC)

Cancer du poumon non à petites cellules

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	18.1
E.1.2	Level	LLT
E.1.2	Classification code	10025055
E.1.2	Term	Lung cancer non-small cell stage IV
E.1.2	System Organ Class	100000004864

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 MEDI4736 + tremelimumab combination therapy compared to SoC in terms of PFS in patients with NSCLC

Comparer l’efficacité de l’association MEDI4736 + tremelimumab à celle du traitement conventionnel en termes de survie sans progression (SSP) chez des patients atteints de CBNPC

E.2.2

Secondary objectives of the trial

To assess the efficacy of MEDI4736 + tremelimumab combination therapy or MEDI4736 monotherapy compared to SoC in terms of PFS, ORR, DoR, APF12, PFS2, and OS

To assess the efficacy of MEDI4736 + tremelimumab combination therapy compared to MEDI4736 monotherapy in terms of PFS and ORR

To assess disease-related symptoms and HRQoL in patients treated with MEDI4736 + tremelimumab and MEDI4736 therapies compared to SoC using the EORTC QLQ C30 v3 and the LC13 module

To assess the PK of MEDI4736 + tremelimumab and MEDI4736 therapies

To investigate the immunogenicity of MEDI4736 and tremelimumab

To assess the safety and tolerability profile of MEDI4736 + tremelimumab and MEDI4736 therapies compared to SoC in the first-line setting for treatment of advanced or metastatic NSCLC patients

Comparer l'efficacité du MEDI4736+tremelimumab ou du MEDI4736 en monothérapie au traitement conventionnel sur SSP, taux de réponse objective (TRO), durée de la réponse (DdR), patients en vie et sans progression 12 mois après la randomisation (SSP12) et survie globale (SG)
Comparer l'efficacité du MEDI4736+tremelimumab et du MEDI4736 en monothérapie en termes de SSP et TRO
Comparer les symptômes liés à la maladie et la qualité de vie liée à la santé chez les patients traités par MEDI4736+tremelimumab ou par MEDI4736 en monothérapie et ceux recevant le traitement conventionnel avec le questionnaire QLQ-C30 v3 de l’EORTC et le module LC13
Évaluer la pharmacocinétique du MEDI4736+tremelimumab et du MEDI4736 en monothérapie
Etudier l'immunogénicité du MEDI4736 et du tremelimumab
Comparer la sécurité d'emploi et la tolérance du MEDI4736+tremelimumab et du MEDI4736 en monothérapie au traitement standard dans le traitement de 1ère ligne du CBNPC de stade avancé ou métastatique

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Inclusion Criteria: For inclusion in the study, patients should fulfill the following criteria:
• Aged at least 18 years
• Documented evidence of Stage IV NSCLC
• No activating EGFR mutation or ALK rearrangement
• No prior chemotherapy or any other systemic therapy for advanced/metastatic NSCLC
• World Health Organization (WHO) Performance Status of 0 or 1

Critères d’inclusion : pour être inclus dans l’étude, les patients doivent présenter la totalité des critères suivants :
• Âge d’au moins 18 ans
• CBNPC de stade IV documenté
• Tumeur dépourvue de mutation activatrice d'EGFR ou de réarrangement d'ALK
• Absence d'antécédent de chimiothérapie ou d'un autre traitement systémique pour CBNPC de stade avancé ou métastatique
• Indice de performance de l'Organisation mondiale de la santé (OMS) de 0 ou 1

E.4

Principal exclusion criteria

- Exclusion Criteria: Patients should not enter the study if any of the following exclusion criteria are fulfilled:
• Mixed small-cell lung cancer and NSCLC histology or not otherwise specified (NSCLC NOS)
• Brain metastases or spinal cord compression unless asymptomatic, treated and stable (not requiring steroids)
• Prior exposure to Immunomodulatory therapy (IMT), including, but not limited to, other anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), anti-programmed cell death1 (PD-1), anti-programmed cell death ligand 1 (PD-L1), or anti PD-L2 antibodies, excluding therapeutic anticancer vaccines
• Active or prior documented inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis)

Critères d’exclusion : les patients ne peuvent pas entrer dans l’étude s’ils présentent l’un des critères d’exclusion suivants :
• Histologie mixte de cancer bronchique à petites cellules et de CBNPC ou non précisée
• Métastases cérébrales ou compression de la moelle épinière, sauf si asymptomatiques, traitées et stables (ne nécessitant pas de corticothérapie)
• Exposition précédente à un traitement à médiation immunitaire, notamment un autre anticorps anti-CTLA-4, anti-PD-1, anti-PD-L1 ou anti-PD-L2, sauf un vaccin thérapeutique antitumoral
• Maladie inflammatoire chronique de l’intestin active ou précédemment documentée (par exemple colite ou maladie de Crohn)

E.5 End points

E.5.1

Primary end point(s)

Progression Free Survival (PFS) using investigator assessments according to Response Evaluation Criteria in Solid Tumours (RECIST 1.1).

Survie sans progression (SSP) selon le jugement de l’investigateur et d’après les critères d’évaluation de la réponse dans les tumeurs solides (Response Evaluation Criteria in Solid Tumors) version RECIST 1.1

E.5.1.1

Timepoint(s) of evaluation of this end point

At baseline, after that every 6 weeks for the first 48 weeks relative to the date of randomization, and then every 8 weeks until progression.

E.5.2

Secondary end point(s)

PFS in patients with PD-L1–negative NSCLC using Investigator assessments according to RECIST 1.1
PFS in patients with PD-L1–positive NSCLC using Investigator assessments according to RECIST 1.1
ORR, DoR, and APF12 using Investigator assessments according to RECIST 1.1
PFS2 using local standard clinical practice OS PFS and ORR using Investigator assessments according to RECIST 1.1
EORTC QLQ-C30, EORTC QLQ-LC13, Changes in World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status will also be assessed.
Concentration of MEDI4736 and tremelimumab in blood and non-compartmental PK parameters, such as peak concentration and trough (as data allow; sparse sampling)
Presence of ADAs for MEDI4736 and tremelimumab

AEs, physical examinations, laboratory findings, and vital signs

. SSP des patients présentant un CBNPC PD-L1- négatif selon le jugement de l’investigateur et d’après les critères RECIST 1.1
. SSP des patients présentant un CBNPC PD-L1- positif selon le jugement de l’investigateur et d’après les critères RECIST 1.1
. TRO, DdR et SSP12 selon le jugement de l’investigateur et d’après les critères RECIST 1.1
. Survie jusqu’à seconde progression (SSP2) déterminée selon la pratique clinique conventionnelle locale
. SG
. SSP et TRO selon le jugement de l’investigateur et d’après les critères RECIST 1.1
. EORTC QLQ-C30, EORTC QLQ-LC13 . Les modifications de l'indice de performance de l’Organisation Mondiale de la Santé (OMS)/Eastern Cooperative Oncology Group (ECOG) seront également évaluées
. Concentrations sanguines du MEDI4736 et du tremelimumab et paramètres pharmacocinétiques non compartimentaux tels que les concentrations maximale et minimale (comme les données le permettront; prélèvements peu fréquents)
. Présence d’anticorps anti-MEDI4736 et anti-tremelimumab

E.5.2.1

Timepoint(s) of evaluation of this end point

For PFS - At baseline, then every 6 weeks for the first 48 weeks relative to the date of randomization, and then every 8 weeks until progression

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

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Platinum-based doublet chemotherapy

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

Australia

Belgium

Canada

France

Germany

Hungary

Italy

Japan

Korea, Republic of

Netherlands

Russian Federation

Spain

Taiwan

Thailand

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

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

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:

455

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

220

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

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Information not present in EudraCT

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

235

F.4.2.2

In the whole clinical trial

675

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.

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

2015-10-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-10-16

P. End of Trial
P.	End of Trial Status	Completed

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Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
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