Clinical Trials Register

Summary
EudraCT Number:	2019-004025-24
Sponsor's Protocol Code Number:	IRFMN-NSCLC-8187
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:	2021-04-21
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

France - ANSM

A.2

EudraCT number

2019-004025-24

A.3

Full title of the trial

BRIDGE trial: Phase II trial of durvalumaB and chemotheRapy Induction followed by Durvalumab and radiotherapy in larGe volumE stage III NSCLC

Essai BRIDGE : Essai de phase II sur le Durvalumab et la chimiothérapie Induction suivie du Durvalumab et de la radiothérapie dans le NSCLC de stade III de grand volume.

A.3.1

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

Study on the activity and safety of a treatment with an antibody in association with chemotherapy in a first phase, and with radiotherapy in a second phase, in patients
with advanced non-small cell lung cancer of large volume

Étude sur l'activité et la sécurité d'un traitement avec un anticorps en association avec une chimiothérapie dans une première phase, et avec une radiothérapie dans une seconde phase, chez des patients atteints de cancer du poumon non à petites cellules avancé de grand volume

A.3.2

Name or abbreviated title of the trial where available

BRIDGE

A.4.1

Sponsor's protocol code number

IRFMN-NSCLC-8187

A.5.4

Other Identifiers

Name:

NCT04765709

Number:

NCT04765709

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	IRCCS - ISTITUTO DI RICERCHE FARMACOLOGICHE MARIO NEGRI
B.1.3.4	Country	Italy
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	AstraZeneca
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	IRCCS - ISTITUTO DI RICERCHE FARMACOLOGICHE MARIO NEGRI
B.5.2	Functional name of contact point	LMRC
B.5.3	Address:
B.5.3.1	Street Address	Via Mario Negri, 2
B.5.3.2	Town/ city	Milan
B.5.3.3	Post code	20156
B.5.3.4	Country	Italy
B.5.4	Telephone number	+390239014661
B.5.5	Fax number	+390233200231
B.5.6	E-mail	bridge@marionegri.it

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	Yes
D.2.1.1.1	Trade name	IMFINZI (50 mg/mL concentrate for solution for infusion, vial of 10 mL of concentrate)
D.2.1.1.2	Name of the Marketing Authorisation holder	ASTRAZENECA AB
D.2.1.2	Country which granted the Marketing Authorisation	France
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.3.4	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.3.11 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)	Yes
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

Locally advanced non-small cell lung cancer in stage III

Cancer des poumons non à petites cellules localement avancé au stade III

E.1.1.1

Medical condition in easily understood language

Advanced lung cancer

Cancer des poumons à un stade avancé

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	20.0
E.1.2	Level	SOC
E.1.2	Classification code	10029104
E.1.2	Term	Neoplasms benign, malignant and unspecified (incl cysts and polyps)
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

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	10029521
E.1.2	Term	Non-small cell lung cancer stage IIIB
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

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	10029519
E.1.2	Term	Non-small cell lung cancer stage III
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

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	10029520
E.1.2	Term	Non-small cell lung cancer stage IIIA
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 increase the proportion of patients with NSCLC in stage III eligible for
immunotherapy plus radiotherapy after induction with durvalumab and chemotherapy, in comparison with historical controls

Augmenter la proportion des patients admissibles pour l’immunothérapie plus la radiothérapie après l’induction par un traitement associant la prise de durvalumab et une chimiothérapie, par rapport aux contrôles historiques.

E.2.2

Secondary objectives of the trial

(1) to evaluate Progression-free Survival (PFS) of patients using RECIST 1.1 criteria according to investigators and blinded central review (BCR); (2) to evaluate response rate of each phase of treatment and the overall response rate using RECIST 1.1 criteria, according to investigators and BCR; (3) to evaluate overall survival (OS) of treated patients; [the trial will assess the efficacy and activity of durvalumab combined with induction chemotherapy, definitive radiotherapy and as consolidation treatment, in terms of PFS, OS and response rate]; (4) to evaluate toxicity and safety of each part of the program.

(1) évaluer la survie sans progression (PFS) des patients en utilisant les critères RECIST 1.1 selon les investigateurs et la revue centrale en aveugle (BCR) ; (2) évaluer le taux de réponse de chaque phase du traitement et le taux de réponse global en utilisant les critères RECIST 1. 1, selon les investigateurs et le BCR ; (3) évaluer la survie globale (OS) des patients traités ; [l'essai évaluera l'efficacité et l'activité du durvalumab associé à la chimiothérapie d'induction, à la radiothérapie définitive et comme traitement de consolidation, en termes de PFS, OS et taux de réponse] ; (4) évaluer la toxicité et la sécurité de chaque partie du programme.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

(1) provision of signed, written and dated informed consent, (2) male or female aged 18 years or older, (3) histologically- or cytologically-documented locally advanced NSCLC (Stage III-v.8 IASLC), (4) patient eligible for platinum-based chemotherapy (platinum – pemetrexed for non-squamous and platinum- vinorelbine for squamous histology), (5) patient not eligible for surgery and chemoradiation (each patient will be discussed in a web multidisciplinary team among all the three involved Cancer Core Europe [CCE] centers) (6) tumor sample requirements: availability of an archived tumor tissue block (or unstained slides to perform local PDL1 assessment following protocol procedure), (7) patient’s willingness to undergo blood draws to provide plasma and blood samples for analysis according to study objectives test for female pre-menopausal patients, (8) life expectancy =12 weeks at the start of treatment, (9) ECOG Performance Status of 0 – 1, (10) Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients, (11) patient willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up, (12) adequate organ and marrow function, (13) absence of a known severe hypersensitivity (= Grade 3) to any of the study chemotherapy agents and/or to durvalumab and/or to any of their excipients.

(1) fourniture d'un consentement éclairé signé, écrit et daté, (2) homme ou femme âgé(e) de 18 ans ou plus, (3) NSCLC localement avancé documenté histologiquement ou cytologiquement (stade III-v.8 IASLC), (4) patient éligible à une chimiothérapie à base de platine (platine - pemetrexed pour une histologie non squameuse et platine - vinorelbine pour une histologie squameuse), (5) patient non éligible à la chirurgie et à la chimioradiation (chaque patient sera discuté au sein d'une équipe multidisciplinaire en ligne entre les trois centres Cancer Core Europe [CCE] impliqués), (6) exigences en matière d'échantillons tumoraux : disponibilité d'un bloc de tissu tumoral archivé (ou de lames non colorées pour effectuer une évaluation locale de PDL1 selon la procédure du protocole), (7) volonté du patient de se soumettre à des prélèvements sanguins pour fournir des échantillons de plasma et de sang à analyser selon les objectifs de l'étude ; test pour les patientes pré-ménopausées, (8) espérance de vie =12 semaines au début du traitement, (9) statut de performance ECOG de 0 - 1, (10) preuve du statut de post-ménopause, ou test de grossesse urinaire ou sérique négatif pour les patientes pré-ménopausées, (11) patient désireux et capable de se conformer au protocole pendant toute la durée de l'étude, y compris de suivre le traitement et les visites et examens prévus, y compris le suivi, (12) fonction adéquate des organes et de la moelle, (13) absence d'hypersensibilité grave connue (= grade 3) à l'un des agents de chimiothérapie de l'étude et/ou au durvalumab et/ou à l'un de leurs excipients.

E.4

Principal exclusion criteria

(1) stage IV NSCLC, (2) patient amenable to curative intent surgery or concurrent
chemoradiation, (3) mixed small cell and non-small cell lung cancer histology, (4)
patients who already received therapy for locally advanced NSCLC, (5) dyspnea of minimal exertion or oxygen requirement, (6) recent medical history of cardiac events during the last 6 months (ischemic or congestive heart failure), (7) pancoast tumors, (8) previous radiotherapy to the thorax (prior to inclusion), including radiotherapy for breast cancer, (9) prior exposure to any anti-PD-1 or anti-PD-L1 antibody, (10) participation in another clinical study with an investigational product during the last 4 weeks (11) any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer
treatment, (12) active or prior documented autoimmune disease within the past 2 years or inflammatory disorders, (13) uncontrolled intercurrent illness including, but not limited to symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses, ongoing or active infection, including any patient known to have evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV) or tuberculosis, psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the patient to give written informed consent, (14) history of another primary malignancy except for: malignancy treated with curative intent and with no known active disease =3 years before the first
dose of study drug and of low potential risk for recurrencem, adequately treated nonmelanoma skin cancer or lentigo maligna without evidence of disease, superficial bladder cancer without evidence of disease, adequately treated carcinoma in situ without evidence of disease, eg, cervical cancer in situ, (15) female patients who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control, (16) any condition that, in the opinion of the Investigator, would interfere with evaluation of the study drug or interpretation of patient safety or study results.

(1) CBNPC de stade IV, (2) patient pouvant bénéficier d'une chirurgie à visée curative ou d'une chimio-radiation simultanée, (3) histologie mixte de cancer du poumon à petites cellules et non à petites cellules, (4) patients ayant déjà reçu un traitement pour un CBNPC localement avancé, (5) dyspnée d'effort minimale ou besoin en oxygène, (6) antécédents médicaux récents d'événements cardiaques au cours des 6 derniers mois (ischémie ou insuffisance cardiaque congestive), (7) tumeurs de Pancoast, (8) radiothérapie antérieure du thorax (avant l'inclusion), y compris radiothérapie pour un cancer du sein, (9) exposition antérieure à tout anticorps anti-PD-1 ou anti-PD-L1, (10) participation à une autre étude clinique avec un produit expérimental au cours des 4 dernières semaines, (11) toute chimiothérapie, immunothérapie, thérapie biologique ou hormonale concomitante pour le traitement du cancer, (12) maladie auto-immune active ou antérieure documentée au cours des 2 dernières années ou troubles inflammatoires, (13) maladie intercurrente non contrôlée, y compris, mais sans s'y limiter, insuffisance cardiaque congestive symptomatique, hypertension non contrôlée, angine de poitrine instable, arythmie cardiaque, ulcère gastroduodénal ou gastrite active, diathèses hémorragiques actives, infection en cours ou active, y compris tout patient connu pour présenter des signes d'hépatite B, d'hépatite C ou de virus de l'immunodéficience humaine (VIH) aigus ou chroniques, ou de tuberculose, maladie psychiatrique/ situations sociales susceptibles de limiter le respect des exigences de l'étude ou de compromettre la capacité du patient à donner son consentement éclairé par écrit, (14) antécédents d'une autre tumeur maligne primaire, à l'exception de :une tumeur maligne traitée à des fins curatives et sans maladie active connue =3 ans avant la première dose du médicament à l'étude et présentant un faible risque potentiel de récidive, un cancer de la peau sans mélanome ou une lentigo maligna traités de manière adéquate sans preuve de maladie, un cancer superficiel de la vessie sans preuve de maladie, un carcinome in situ traité de manière adéquate sans preuve de maladie, (15) les patientes enceintes, allaitantes ou les patients masculins ou féminins en âge de procréer qui n'utilisent pas une méthode efficace de contrôle des naissances, (16) toute condition qui, selon l'investigateur, pourrait interférer avec l'évaluation du médicament à l'étude ou l'interprétation de la sécurité du patient ou des résultats de l'étude.

E.5 End points

E.5.1

Primary end point(s)

proportion of patients who did not progress and who achieved a mean lung dose <20 Gy and/or a lung V20<35% (response)

Proportion de patients qui n'ont pas progressé et qui ont obtenu une dose moyenne au poumon <20 Gy et/ou un V20<35% (réponse)

E.5.1.1

Timepoint(s) of evaluation of this end point

At the end of part 1 of the study (induction with durvalumab + chemotherapy). In
particular, the study has a Simon 2 stages design and the firt assessment of
primary endpoint will be performed when 37 patients are enrolled

À la fin de la partie 1 de l'étude (induction par un traitement associant la prise de durvalumab et une chimiothérapie). En particulier, cette étude possède un design à 2 étapes de Simon, et la première évaluation du critère principal sera effectuée lorsque 37 patients auront été recrutés.

E.5.2

Secondary end point(s)

1) Progression Free Survival (PFS)
2) Overall Survival (OS)
3) Objective Response Rate (ORR)
4) SECONDARY SAFETY ENDPOINTS: to assess adverse reactions (ARs) and the frequency and nature of serious adverse events (SAEs).

1) Survie sans progression ( PFS)
2) Survie globale (OS)
3) Taux de réponse objectif (ORR)
4) Objectifs secondaires de sécurité : évaluer les effets indésirables (EI) ainsi que la fréquence et la nature des effets indésirables graves (EIG).

E.5.2.1

Timepoint(s) of evaluation of this end point

1) PFS: is defined as the time from the date of start of induction treatment until the date of objective disease progression (using RECIST 1.1 criteria according to
investigators and blinded central review (BCR)) or death to any cause whichever
comes first.
2) OS: is defined as the time from the date of start of induction treatment until
death due to any cause.
3) ORR: is defined as the proportion of patients with CR or PR (as best response)
according to RECIST 1.1 as assessed by Investigators and BCR; ORR will be presented for each of the three phases of the trial and overall.
4) SECONDARY SAFETY ENDPOINTS: will be evaluated during all the course of treatment and follow-up.

1) SSP : définie comme le temps écoulé entre la date de début du traitement d'induction et la date de progression objective de la maladie (selon les critères RECIST 1.1, selon les investigateurs et l'examen central en aveugle (BCR)) ou le décès, quelle qu'en soit la cause, selon la première éventualité.
2) OS : est défini comme le temps écoulé entre la date du début du traitement d'induction et le décès, quelle qu'en soit la cause.
3) ORR : est défini comme la proportion de patients ayant une RC ou une RP (meilleure réponse) selon RECIST 1.1, évaluée par les investigateurs et le BICR ; l'ORR sera présenté pour chacune des trois phases de l'essai et globalement.
4) Objectifs secondaires de sécurité : ils seront évalués pendant toute la durée du traitement et du suivi.

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

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

multicentrique, ouvert, simple bras, Simon 2 étapes

multicentric, open label, single arm, Simon 2 stages

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

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

Yes

E.8.4

The trial involves multiple sites in the 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

E.8.6.2

Trial being conducted completely outside of the EEA

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 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:

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

F.4.2.2

In the whole clinical trial

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)

Patients will be treated according to clinical practice

Les patients seront traités conformément à la pratique clinique

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

2021-09-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-10-20

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

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials