Clinical Trials Register

Summary
EudraCT Number:	2011-004792-36
Sponsor's Protocol Code Number:	CA209-017
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-07-25
Trial results	View 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

2011-004792-36

A.3

Full title of the trial

An Open-Label Randomized Phase III Trial of BMS-936558 versus Docetaxel in Previously Treated Advanced or Metastatic Squamous Cell Non-small Cell Lung Cancer (NSCLC).

Studio di fase III randomizzato in aperto di BMS-936558 verso Docetaxel in soggetti con carcinoma polmonare squamoso non a piccole cellule (NSCLC), in stadio avanzato o metastatico precedentemente trattato

A.3.1

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

Study of BMS-936558 compared to Docetaxel in previously treated advanced or metastatic Squamous cell NSCLC.

Studio di confronto tra BMS-936558 e Docetaxel in soggetti con carcinoma polmonare squamoso non a piccole cellule (NSCLC) avanzato o metastatico precedentemente trattato.

A.4.1

Sponsor's protocol code number

CA209-017

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	BRISTOL-MYERS SQUIBB INTERNATIONAL CORPORATION
B.1.3.4	Country	Belgium
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	Bristol-Myers Squibb International Corporation
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Bristol-Myers Squibb International Corporation
B.5.2	Functional name of contact point	EU Study Start-Up Unit
B.5.3	Address:
B.5.3.1	Street Address	Parc de l'Alliance - Avenue de Finlande, 8
B.5.3.2	Town/ city	Braine-l'Alleud
B.5.3.3	Post code	1420
B.5.3.4	Country	Belgium
B.5.6	E-mail	clinical.trials@bms.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	NA
D.3.2	Product code	BMS-936558
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.3.9.1	CAS number	946414-94-4
D.3.9.2	Current sponsor code	BMS-936558-01
D.3.9.3	Other descriptive name	Anti-PD-1 Human Monoclonal Antibody; MDX-1106
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	10
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	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	Taxotere 160 mg (20 mg/mL)
D.2.1.1.2	Name of the Marketing Authorisation holder	Aventis Pharma S.A
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.3.4	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	DOCETAXEL
D.3.9.1	CAS number	114977-28-5
D.3.9.4	EV Substance Code	SUB12492MIG
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	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

Squamous cell Non-small cell lung cancer

Carcinoma polmonare squamoso non a piccole cellule (NSCLC)

E.1.1.1

Medical condition in easily understood language

Squamous cell Non-small cell lung cancer

Carcinoma Polmonare squamoso non a piccole cellule (NSCLC)

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	14.1
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

The purpose of the study is to compare the change in tumor size, and overall survival of BMS-936558 as compared with Docetaxel in subjects with squamous cell non-small cell lung cancer (NSCLC), after failure of prior platinum-based chemotherapy

L’obiettivo principale dello studio è confrontare la variazione della dimensione del tumore e la sopravvivenza complessiva indotti da BMS-936558 rispetto a Docetaxel in soggetti con carcinoma polmonare squamoso non a piccole cellule che hanno fallito una precedente chemioterapia contenente platino.

E.2.2

Secondary objectives of the trial

.To compare the progression-free survival (PFS) of BMS-936558 versus docetaxel 2.To evaluate clinical benefit in terms of ORR and OS of BMS-936558 versus docetaxel, in PD-L1 + versus PD-L1- protein expression subgroups 3.To evaluate durability of and time to objective response in BMS-936558 and docetaxel groups 4.To evaluate the proportion of subjects exhibiting disease-related symptom progression, as measured by LCSS, in BMS-936558 and docetaxel groups

1.Confrontare la sopravvivenza libera da progressione (PFS) indotta da BMS-936558 rispetto a Docetaxel 2.Valutare il beneficio clinico in termini di percentuale di risposta obiettiva (ORR) e sopravvivenza complessiva (OS) indotte da BMS-936558 rispetto a Docetaxel nel sottogruppo di soggetti positivi all’espressione della proteina PD-L1 rispetto a quelli che non esprimono la proteina PD-L1 3.Valutare la durata e il tempo alla risposta obiettiva tra i due bracci, BMS-936558 e Docetaxel 4.Valutare la percentuale di soggetti che mostrano sintomi di progressione correlati alla malattia, misurati attraverso la specifica scala di valutazione LCSS, nei due bracci BMS-936558 e Docetaxel.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1) men & women ≥ 18 years of age 2) Subjects with histologically or cytologically-documented squamous cell NSCLC who present with Stage IIIB/IV disease or recurrent disease following radiation therapy or surgical resection. 3) Disease recurrence or progression during/after one prior platinum-containing chemotherapy regimen for advanced or metastatic disease 4) Measurable disease by CT/MRI per RECIST 1.1 criteria 5) ECOG performance status ≤ 1 6) An FFPE tumor tissue block or unstained slides of tumor sample (archival or recent) must be available for biomarker evaluation. Specimens must be received by the central lab prior to randomization. Biopsy should be excisional, incisional or core needle. Fine needle aspiration is insufficient.

1.Uomini e donne di età maggiore o uguale a 18 anni 2.Soggetti con carcinoma polmonare squamoso non a piccole cellule (NSCLC), documentato in termini istologici o citologici, con malattia allo stadio IIIB/IV o recidivante dopo radioterapia o rimozione chirurgica 3.Malattia recidivante o che è andata in progressione durante o dopo un precedente regime di chemioterapia contenente platino 4.Malattia misurabile tramite TAC/RMN sulla base dei criteri RECIST 1.1 5.Performance Status inferiore o uguale a 1 (ECOG) 6.Blocchetto di tessuto tumorale fissato in formalina e incluso in paraffina o vetrini non colorati contenenti sezioni di tessuto (di archivio o recenti) devono essere disponibili per l’analisi dei biomarker. Tali campioni devono essere ricevuti dal laboratorio centralizzato prima della randomizzazione. Il tessuto deve provenire da una biopsia escissionale, incisionale o ago aspirato profondo. L’ago aspirato sottile non è sufficiente.

E.4

Principal exclusion criteria

1) Subjects with active CNS metastases are excluded. Subjects are eligible if CNS metastases are adequately treated and subjects are neurologically returned to baseline for at least 2 weeks prior to enrollment. In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of ≤10mg daily prednisone (or equivalent) 2) Subjects with carcinomatous meningitis. 3) Subjects with active, known or suspected autoimmune disease, or subjects with interstitial lung disease. 4) Subjects with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of randomization. 5) Prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways). 6) Prior treatment on the first line study CA184104 first line NSCLC study 7) Prior treatment with docetaxel 8) Treatment with any investigational agent within 28 days of first administration of study treatment

1.Soggetti con metastatasi attive del sistema nervoso centrale sono esclusi. Tali soggetti possono essere inclusi se le metastasi sono adeguatamente trattate e i soggetti sono rientrati nel basale neurologico da almeno 2 settimane prima dell’arruolamento. Inoltre tali soggetti devono essere fuori dal trattamento con corticosteroidi o in dose stabile o decrescente inferiore o uguale a 10 mg di prednisone (o equivalenti). 2.Soggetti con meningite carcinomatosa 3.Soggetti con malattia autoimmune attiva, nota o sospetta, o soggetti con malattia polmonare interstiziale 4.Soggetti con una condizione clinica che richieda trattamento sistemico sia con corticosteroidi o altri farmaci immunosoppressivi nell’arco dei 14 giorni precedenti alla randomizzazione 5.Precedente trattamento con terapia anti-PD-1, anti-PD-L1, anti-PD.L2, anti-CD137, o anticorpo anti-CTLA-4 (incluso ipilimumab o qualunque altro anticorpo o farmaco che abbia come target specifico la costimolazione delle cellule T) 6.Precedente trattamento nello studio BMS CA184-104, Ipilimumab prima linea nel tumore al polmone non a piccole cellule (NSCLC). 7.Precedente trattamento con Docetaxel 8.Trattamento con altri farmaci sperimentati nell’arco dei 28 giorni precedenti l’inizio della terapia con il farmaco in studio.

E.5 End points

E.5.1

Primary end point(s)

Objective Response Rate, Overall Survival

Percentuale di Risposta Obiettiva (ORR), Sopravvivenza Complessiva (OS)

E.5.1.1

Timepoint(s) of evaluation of this end point

24 MONTHS

24 MESI

E.5.2

Secondary end point(s)

1.To compare the progression-free survival (PFS) of BMS-936558 versus docetaxel 2.To evaluate clinical benefit in terms of ORR and OS of BMS-936558 versus docetaxel, in PD-L1 + versus PD-L1- protein expression subgroups 3.To evaluate durability of and time to objective response in BMS-936558 and docetaxel groups 4.To evaluate the proportion of subjects exhibiting disease-related symptom progression, as measured by LCSS, in BMS-936558 and docetaxel groups.

1. Confrontare la sopravvivenza libera da progressione (PFS) indotta da BMS-936558 rispetto a Docetaxel 2. Valutare il beneficio clinico in termini di percentuale di risposta obiettiva (ORR) e sopravvivenza complessiva (OS) indotte da BMS-936558 rispetto a Docetaxel nel sottogruppo di soggetti positivi all’espressione della proteina PD-L1 rispetto a quelli che non esprimono la proteina PD-L1 3. Valutare la durata e il tempo alla risposta obiettiva tra i due bracci, BMS-936558 e Docetaxel 4. Valutare la percentuale di soggetti che mostrano sintomi di progressione correlati alla malattia, misurati attraverso la specifica scala di valutazione LCSS, nei due bracci BMS-936558 e Docetaxel

E.5.2.1

Timepoint(s) of evaluation of this end point

24 MONTHS

24 MESI

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

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Biomarker,Immunogenicity,Outcomes Research Assessments:LCSS&EuroPRO Group’s EQ-5D

Valutazione Biomarker, Immunogenicità, Risultati Ricerca: LCSS &EuroPRO Group’s EQ-5D

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

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

Australia

Brazil

Canada

Chile

Hong Kong

Mexico

Peru

Russian Federation

Singapore

South Africa

Turkey

United States

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

This study will end when analysis of survival is complete. All subjects will be followed for overall survival every 3 months until death, lost to follow-up, or withdrawal of study consent. The duration of study will be approximately 2 years (24 months).

Lo studio si concluderà dopo completamento dell'analisi della sopravvivenza.Tutti i soggetti saranno seguiti per la sopravvivenza complessiva ogni 3 mesi fino a decesso, perdita al follow up,ritiro del consenso. Durata dello studio: circa 2 anni

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

Number of subjects for this age range:

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:

160

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

100

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

190

F.4.2.2

In the whole clinical trial

320

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)

At the conclusion of the study, subjects who continue to demonstrate clinical benefit will be eligible to receive study drug. Study drug will be provided via an extension of the study, a rollover study requiring approval by responsible health authority and ethics committee, or through another mechanism at the discretion of the sponsor. See also Protocol, section 3.2 for more details.

Al termine dello studio i pazienti che continueranno a dimostrare un beneficio clinico saranno idonei a ricevere ancora il farmaco in studio. Il farmaco sarà fornito attraverso una estensione del presente studio o tramite uno studio di roll-over che richiederà l’approvazione del comitato etico, o attraverso un altro procedimento consentito dalla legge a discrezione dello sponsor. Per ulteriori dettagli vedi protocollo sezione 3.2

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

2012-10-25

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-07-18

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

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IMP with orphan designation in the indication
Orphan Designation Number:
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