Clinical Trials Register

Summary
EudraCT Number:	2016-000603-91
Sponsor's Protocol Code Number:	CA013-004
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:	2021-06-17
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

2016-000603-91

A.3

Full title of the trial

A Phase 1/2a Study of BMS-986179 Administered Alone and in Combination with N ivolumab (BMS-936558) in Subjects with Advanced Solid Tumors

Studio di fase 1/2a di BMS-986179 somministrato in monoterapia e in combinazione con nivolumab (BMS-936558) in soggetti con tumori solidi in stadio avanzato

A.3.1

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

Study of BMS-986179 Administered alone and in Combination with Nivolumab (BMS-
936558) in Subjects with Advanced Solid Tumors

Studio di BMS-986179 somministrato in monoterapia e in combinazione con nivolumab (BMS-936558) in soggetti con tumori solidi in stadio avanzato

A.3.2

Name or abbreviated title of the trial where available

ooo

A.4.1

Sponsor's protocol code number

CA013-004

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02754141

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1179-3950

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	Milagros Blazquez
B.5.3	Address:
B.5.3.1	Street Address	Parc de l'Alliance - Avenue de Finlande, 4
B.5.3.2	Town/ city	Braine-l'Alleud
B.5.3.3	Post code	1420
B.5.3.4	Country	Belgium
B.5.4	Telephone number	0000000
B.5.5	Fax number	0000000
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.2.1.2	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	NIVOLUMAB - 10ml vial - clinical
D.3.2	Product code	[BMS-936558]
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	NIVOLUMAB
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	BMS936558; BMS-936558, MDX1106, ONO-4538
D.3.9.4	EV Substance Code	SUB32944
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	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	No
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	NIVOLUMAB - 4ml vial - clinical
D.3.2	Product code	BMS-936558
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	NIVOLUMAB
D.3.9.1	CAS number	946414-94-4
D.3.9.2	Current sponsor code	BMS-936558
D.3.9.3	Other descriptive name	BMS936558,BMS-936558, MDX1106, ONO-4538
D.3.9.4	EV Substance Code	SUB32944
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	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	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	Anti-CD73
D.3.2	Product code	[BMS-986179]
D.3.4	Pharmaceutical form	Solution for injection
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	Anti CD73
D.3.9.2	Current sponsor code	CA013-004
D.3.9.3	Other descriptive name	BMS986179
D.3.9.4	EV Substance Code	SUB181628
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	35
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: 4
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	Opdivo (100 mg/10 ml)
D.2.1.1.2	Name of the Marketing Authorisation holder	Bristol-Myers Squibb Pharma 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	NIVOLUMAB - 10ml vial- COMMERCIAL
D.3.2	Product code	[BMS-936558]
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	NIVOLUMAB
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	BMS936558; BMS-936558, MDX1106, ONO-4538
D.3.9.4	EV Substance Code	SUB32944
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	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: 5
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	Opdivo (40 mg/4 ml)
D.2.1.1.2	Name of the Marketing Authorisation holder	Bristol-Myers Squibb Pharma 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	NIVOLUMAB - 4ml vial- COMMERCIAL
D.3.2	Product code	[BMS-936558]
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	NIVOLUMAB
D.3.9.1	CAS number	946414-94-4
D.3.9.2	Current sponsor code	BMS-936558
D.3.9.3	Other descriptive name	BMS936558,BMS-936558, MDX1106, ONO-4538
D.3.9.4	EV Substance Code	SUB32944
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	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.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

Solid tumors

Tumori solidi

E.1.1.1

Medical condition in easily understood language

Solid tumors

Tumori solidi

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	LLT
E.1.2	Classification code	10065252
E.1.2	Term	Solid tumor
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

The primary objective is to assess the safety and tolerability of BMS-
986179 administered alone and in combination with nivolumab.

Valutare la sicurezza e la tollerabilità di BMS-986179 somministrato in monoterapia e in combinazione con nivolumab

E.2.2

Secondary objectives of the trial

-) To characterize the PD activity of BMS-986179 administered alone and
in combination with nivolumab
-) To assess the preliminary anti-tumor activity of BMS-986179 in
combination with nivolumab as measured by ORR, DOR, and
progression-free survival rate (PFSR)
-) To characterize the PK and immunogenicity of BMS-986179
administered alone and in
combination with nivolumab
-) To characterize the immunogenicity of nivolumab when administered
in combination with
BMS-986179

• Caratterizzare la farmacodinamica (Pharmacodynamic, PD) di BMS-986179 somministrato in monoterapia e in combinazione con nivolumab
• Valutare l’attività antitumorale preliminare di BMS-986179 in monoterapia e in combinazione con nivolumab misurata in base al tasso di risposta obiettiva (Objective Response Rate, ORR), durata della risposta (Duration of Response, DOR) e tasso di sopravvivenza libera da progressione (Progression-Free Survival Rate, PFSR)
• Caratterizzare la farmacocinetica (Pharmacokinetics, PK) e l’immunogenicità di BMS-986179 somministrato in monoterapia e in combinazione con nivolumab
• Caratterizzare l’immunogenicità di nivolumab somministrato in combinazione con BMS-986179

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Pharmacogenetics
Version: 6.0
Date: 20/10/2017
Title: A Phase 1/2a Study of BMS-986179 Administered alone and in
Combination with Nivolumab (BMS- 936558) in Subjects with Advanced
Solid Tumors.
Objectives: Additional research samples and the data they generate are used by BMS researchers, and a variety of collaboration partners, to continue to explore the science behind both our drugs and the causes and mechanism of disease and how to effectively treat patients beyond the timeframe of the study, including their use in the development and/or validation of companion diagnostics to support the use of a particular therapy. These samples and their related data may also be used together with samples and data from other clinical studies to support this expanded research.

Pharmacogenomics
Version: 6.0
Date: 20/10/2017
Title: A Phase 1/2a Study of BMS-986179 Administered alone and in
Combination with Nivolumab (BMS- 936558) in Subjects with Advanced
Solid Tumors.
Objectives: Additional research samples and the data they generate are used by BMS researchers, and a variety of collaboration partners, to continue to explore the science behind both our drugs and the causes and mechanism of disease and how to effectively treat patients beyond the timeframe of the study, including their use in the development and/or validation of companion diagnostics to support the use of a particular therapy. These samples and their related data may also be used together with samples and data from other clinical studies to support this expanded research.

Other types of substudies
Specify title, date and version of each substudy with relative objectives: Part 1B is a substudy

Farmacogenetica
Versione: 6.0
Data: 20/10/2017
Titolo: Studio di fase 1/2a di BMS-986179 somministrato in monoterapia e in combinazione
con nivolumab (BMS-936558) in soggetti con tumori solidi in stadio avanzato, sezione 5.10 del protocollo

Obiettivi: Questi campioni e i dati che saranno generati da questa ricerca addizionale saranno utilizzati dai ricercatori di BMS per continuare ad esplorare le caratteristiche dei farmaci B-MS -986179 e Anti-CD73, le cause e il meccanismo delle patologie in studio e come trattare efficacemente i pazienti oltre la durata dello studio, compreso il loro uso nello sviluppo e/o nella convalida di sistemi diagnostici per supportare l'uso di una particolare terapia. Questi campioni e i relativi dati potrebbero anche essere utilizzato insieme ai campioni e ai dati provenienti da altri studi clinici per ampliare questa ricerca.

Farmacogenomica
Versione: 6.0
Data: 20/10/2017
Titolo: Studio di fase 1/2a di BMS-986179 somministrato in monoterapia e in combinazione
con nivolumab (BMS-936558) in soggetti con tumori solidi in stadio avanzato, sezione 5.10 del protocollo
Obiettivi: Questi campioni e i dati che saranno generati da questa ricerca addizionale saranno utilizzati dai ricercatori di BMS per continuare ad esplorare le caratteristiche dei farmaci B-MS -986179 e Anti-CD73, le cause e il meccanismo delle patologie in studio e come trattare efficacemente i pazienti oltre la durata dello studio, compreso il loro uso nello sviluppo e/o nella convalida di sistemi diagnostici per supportare l'uso di una particolare terapia. Questi campioni e i relativi dati potrebbero anche essere utilizzato insieme ai campioni e ai dati provenienti da altri studi clinici per ampliare questa ricerca.

Altre tipologie di sottostudi
specificare il titolo, la data e la versione di ogni sottostudio con i relativi obiettivi: parte 1B è un sottostudio
NOTA: ma non è applicabile in Italia

E.3

Principal inclusion criteria

- Men and women at least 18 years of age
- Advanced solid tumors
- Eastern Cooperative Oncology Group (ECOG) 0-1
- Acceptable lab testing results
- Allow biopsies

- Uomini e donne di almeno 18 anni di età;
- Tumori solidi avanzati;
- Eastern Cooperative Oncology Group (ECOG) 0-1
- Risultati dei test di laboratorio accettabili
- Consenso all’esecuzione di biopsie

E.4

Principal exclusion criteria

- Central nervous system (CNS) tumors
- Uncontrolled or significant cardiovascular diseases
- Active or known autoimmune disease
- Organ transplant

- Tumori del sistema nervoso centrale (SNC)
- Malattie cardiovascolari non sotto controllo o significative
- Malattia autoimmune nota o attiva
- Trapianto d'organo

E.5 End points

E.5.1

Primary end point(s)

The primary objective of the study is to assess the safety and tolerability
of BMS-986179 administered alone and in combination with nivolumab.
The assessment of safety will be based on the incidence of AEs, SAEs,
AEs leading to discontinuation, and deaths in relation to initial
treatment. In addition, clinical laboratory test abnormalities will be
examined.

L’obiettivo primario è valutare la sicurezza e la tollerabilità di BMS-986179 somministrato in monoterapia e in combinazione con nivolumab. La valutazione della sicurezza sarà basata sull'incidenza di AE, SAE che determineranno la sospensione del trattamento e ai decessi in relazione al trattamento iniziale. Inoltre, saranno valutate le anomalie cliniche nei test di laboratorio.

E.5.1.1

Timepoint(s) of evaluation of this end point

see above section

Vedi la sezione di cui sopra

E.5.2

Secondary end point(s)

The first secondary objective (PD effect of CD73 inhibition) will be
measured by CD73 enzyme assays and CD73 IHC in pre- and ontreatment
tumor biopsies.
The anti-tumor activity of BMS-986179 in combination with nivolumab
will be measured by ORR, DOR, and PFSR at 24 weeks and will be based
on RECIST 1.1 for solid tumors. These anti-tumor assessments may also
be performed periodically on an exploratory basis after the 24-week time
point as warranted by the data. Disease assessment with CT and/or MRI
as appropriate will be performed at baseline, every 8 weeks from the
start of combination treatment for the Q1W, Q2W and Q4W regimens, or
every 9 weeks from the start of combination treatment for the Q3W
regimen until treatment discontinuation or completion, and then every
12 weeks for the first year until further disease progression, start of a
new treatment, lost to follow-up, or death, whichever comes first.
The PK will be characterized by assessment of PK parameters of BMS-
986179, and immunogenicity will be assessed by the frequency of
positive ADA to BMS-986179 and nivolumab.

Il primo obiettivo secondario (effetto PD dell'inibizione di CD73) sarà misurato mediante l’analisi enzimatica CD73 e CD73 IHC sui campioni bioptici prima del trattamento e durante il trattamento dello studio.

L'attività antitumorale di BMS-986179 in combinazione con nivolumab sarà misurata da ORR, DOR e PFSR a 24 settimane e sarà basata sul RECIST 1.1 per i tumori solidi. Queste valutazioni antitumorali potranno essere eseguite anche periodicamente su base esplorativa dopo le 24 settimane.

La valutazione della malattia con TC e/o risonanza magnetica sarà eseguita al basale, ogni 8 settimane dall’inizio del trattamento di combinazione per i regimi Q1W, Q2W e Q4W o
ogni 9 settimane dall'inizio del trattamento combinato per il regime Q3W fino alla sospensione o al completamento del trattamento, e poi per tutti i regimi ogni 12 settimane per il primo anno fino all'ulteriore progressione della malattia, inizio di un nuovo trattamento, perso al follow-up o alla morte, a seconda dell'evento che si verifica per primo.

La PK sarà caratterizzata dalla valutazione dei parametri PK di BMS- 986179 e l'immunogenicità sarà valutata dalla frequenza di ADA positivo a BMS-986179 e nivolumab.

E.5.2.1

Timepoint(s) of evaluation of this end point

see above section.

Vedi la sezione di cui sopra

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

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

Yes

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)

Yes

E.7.1.1

First administration to humans

Yes

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

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

E.8.1.1 - Randomizzato E.8.1.2 - In aperto

Randomised:, open

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

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

Canada

Israel

United States

France

Germany

Italy

Netherlands

E.8.7

Trial has a data monitoring committee

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

LPLV

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:

298

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

372

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 end of the study, BMS will not continue to provide BMS-supplied
study drug to subjects/investigators unless BMS chooses to extend the
study.

Alla fine dello studio, BMS non continuerà a fornire i farmaci in studio, a meno che BMS scelga di estendere lo studio. Lo sperimentatore di ciascun centro dovrà assicurarsi che i pazienti partecipanti ricevano lo Standard of Care appropriato per trattare la loro malattia

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

2018-03-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-12-20

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

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Select Trial Status:	Select Trial Phase:
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Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
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