Clinical Trials Register

Summary
EudraCT Number:	2015-004914-79
Sponsor's Protocol Code Number:	CA017-003
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

2015-004914-79

A.3

Full title of the trial

A Phase 1/2a Study of BMS-986205 Administered in Combination with Nivolumab (anti-PD-1 Monoclonal Antibody) and in Combination with Both Nivolumab and Ipilimumab (anti-CTLA-4 Monoclonal Antibody) in Advanced Malignant Tumors

Studio clinico di fase 1/2a di BMS-986205 in combinazione con Nivolumab (anticorpo monoclonale anti PD-1) ed in combinazione con NIvolumab ed Ipilimumab (anticorpo monoclonale anti-CTLA-4) in tumori in stadio avanzato

A.3.1

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

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

CA017-003

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02658890

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1173-1719

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, 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	000000
B.5.5	Fax number	000000
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	Nivolumab
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.3.8	INN - Proposed INN	Nivolumab
D.3.9.1	CAS number	946414-94-4
D.3.9.2	Current sponsor code	BMS-936558-01
D.3.9.4	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.2.5	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	IDO-1 inhibitor
D.3.2	Product code	[BMS-986205]
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	BMS-986205
D.3.9.2	Current sponsor code	BMS-986205-04
D.3.9.4	EV Substance Code	SUB179973
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
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	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	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: 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	IDO-1 inhibitor
D.3.2	Product code	[BMS-986205]
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	BMS-986205
D.3.9.2	Current sponsor code	BMS-986205-04
D.3.9.4	EV Substance Code	SUB179973
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
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	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	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	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	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	IDO-1 inibitore
D.3.2	Product code	[BMS-986205]
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	BMS-986205
D.3.9.2	Current sponsor code	BMS-986205-04
D.3.9.4	EV Substance Code	SUB179973
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
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	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	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	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	Yervoy
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	Ipilimumab
D.3.2	Product code	BMS-734016
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	ipilimumab
D.3.9.1	CAS number	477202-00-9
D.3.9.2	Current sponsor code	BMS-734016
D.3.9.3	Other descriptive name	BMS734016/MDX010
D.3.9.4	EV Substance Code	SUB22577
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	5
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: 6
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.2.1.2	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	Powder and solvent 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
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	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	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	IDO-1 inhibitor
D.3.2	Product code	BMS-986205
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	BMS-986205
D.3.9.2	Current sponsor code	BMS-986205-04
D.3.9.3	Other descriptive name	BMS986205, BMS-986205
D.3.9.4	EV Substance Code	SUB179973
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25
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	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	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: 8
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	IDO-1 inhibitor
D.3.2	Product code	BMS-986205
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	BMS-986205
D.3.9.2	Current sponsor code	BMS-986205-04
D.3.9.3	Other descriptive name	BMS986205, BMS-986205
D.3.9.4	EV Substance Code	SUB179973
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
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	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	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	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 Malignant Tumors

Tumori in stadio avanzato

E.1.1.1

Medical condition in easily understood language

Advanced Malignant Tumors

Tumori in stadio avanzato

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	21.0
E.1.2	Level	LLT
E.1.2	Classification code	10048683
E.1.2	Term	Advanced cancer
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

Part 1: dose scalation: to determine the safety, tolerability, dose limiting toxicities (DLTs), and maximum tolerated dose (MTD)/maximum
administered dose (MAD)/alternate dose of BMS-986205 administered as monotherapy and in combination with nivolumab in subjects with
advanced malignant tumors.
Part 2: Dose Expansion:
To investigate the anti-tumor activity of BMS-986205 administered in
combination with nivolumab in distinct cohorts of subjects with
advanced malignant tumors.
To evaluate the safety and tolerability of BMS-986205 in combination
with nivolumab in subjects with advanced malignant tumors.
Part 3: BMS-986205, Nivolumab and Ipilimumab Combination
To determine the safety, tolerability, dose-limiting toxicities (DLTs), and
preliminary anti-tumor activity of BMS-986205 administered in
combination with both nivolumab and ipilimumab in subjects with select
advanced malignant tumors.

Parte 1: incremento della dose: valutare la sicurezza, la tollerabilità, le tossicità dose-limitanti (DLTs) e le dosi MTD/MAD/alternativa di BMS-986205 somministrato in monoterapia e in combinazione con nivolumab in soggetti affetti da tumori in stadio avanzato.
Parte 2: Espansione della dose
Determinare l’attività antitumorale di BMS-986205 somministrato in combinazione con nivolumab in coorti distinte di soggetti come tumori in stadio avnzato.
Valutare la sicurezza e la tollerabilità di BMS-986205 in combinazione con nivolumab in soggetti con tumori in stadio avanzato.
Parte 3: combinazione di BMS-986205, nivolumab ed ipilimumab
Determinare la sicurezza, la tollerabilità e le tossicità dose-limitanti (DLTs) e l’attività antitumorale preliminare di BMS-986205 somministrato in combinazione con nivolumab ed ipilimumab in soggetti con determinati tumori in stadio avanzato.

E.2.2

Secondary objectives of the trial

- To characterize the pharmacokinetics (PK) of BMS-986205
administered alone, in combination with nivolumab, and in combination
with both nivolumab and ipilimumab.
- To investigate the anti-tumor activity of BMS-986205 administered in
combination with nivolumab in dose escalation and clinical
pharmacology substudies.
- To characterize the pharmacodynamic activity of BMS-986205
administered alone, in combination with nivolumab, and in combination
with both nivolumab and ipilimumab.
- To characterize the immunogenicity of nivolumab when administered in
combination with BMS-986205 and in combination with both BMS-
986205 and ipilimumab.
- To characterize the immunogenicity of ipilimumab when administered
in combination with nivolumab and BMS-986205

• Caratterizzare la farmacocinetica (PK) di BMS-986205 somministrato in monoterapia e in combinazione con nivolumab e in combinazione con nivolumab ed ipilimumab.
• studiare l’attività antitumorale di BMS-986205 somministrato in combinazione con nivolumab nella fase di incremento della dose e nei sottostudi di farmacologia.
• Caratterizzare la farmacodinamica di BMS-986205 somministrato in monoterapia e in combinazione con nivolumab e in combinazione con nivolumab ed ipilimumab.
• Caratterizzare l’immunogenicità di nivolumab somministrato in combinazione con BMS-986205 e in combinazione con BMS-986205 ed ipilimumab.
• Caratterizzare l’immunogenicità di ipilimumab somministrato in combinazione con nivolumab e BMS-986205.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• During dose escalation, subjects with advanced solid tumors that have
progressed following at least one standard regimen
• During cohort expansion, subjects with various solid tumors that either
have received at least one prior therapy or are treatment naive,
depending on the specified tumor type
• Subjects must have measurable disease
• Subject must consent to provide previously collected tumor tissue and
must consent to a repeat tumor biopsy during screening.
• Women and men > / =18 years of age with performance status of 0 or 1
• At least 4 weeks since any previous treatment for cancer
• Must be able to swallow pills or capsules
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1

• Per l’incremento della dose, soggetti affetti da tumore solido che hanno avuto una progressione di malattia dopo il trattamento con almeno una terapia standard
• Per l’espansione della dose, soggetti con diversi tumori solidi che, a seconda della specifica tipologia di tumore, hanno ricevuto almeno una precedente terapia oppure sono naive
• i soggetti devono avere una malattia misurabile
• i soggetti devono acconsentire a fornire tessuto tumorale raccolto prima della partecipazione allo studio e devono acconsentire a ripetere una biopsia durante la fase di screening dello studio.
• donne e uomini con età superiore o uguale a 18 anni con performance status di 0 oppure 1
• almeno 4 settimane senza aver ricevuto una terapia anti-tumorale
• in grado di ingerire pillole oppure capsule
• ECOG Performance Status 0-1

E.4

Principal exclusion criteria

• Active or chronic autoimmune diseases
• Uncontrolled or significant cardiovascular disease
• Chronic hepatitis
Positive test for Hepatitis B virus surface antigen or Hepatitis C
antibody (except for subjects with hepatocellular carcinoma)Other
protocol defined inclusion/exclusion criteria could apply
• Uncontrolled or significant cardiovascular disease
• Active infection
• History of any chronic Hepatitis, active Hepatitis B or C, human
immunodeficiency virus(HIV), or acquired immune deficiency
syndrome(AIDS)
• Active Central nervous system (CNS) metastases and CNS metastases
as the only sites of disease

• Malattia autoimmune attiva o cronica
• Patologia cardiovascolare incontrollata o di grado significativo
• epatite cronica, test positivo per l’antigene di superficie dell’epatite B oppure per l’anticorpo epatite C (ad eccezione dei pazienti affetti da carcinoma epatocellulare). Si possono applicare anche altri criteri di inclusione/esclusione in accordo al protocollo
• Infezione attiva
• Storia di epatite cronica, epatite B o C attiva, virus dell’immunodeficienza umana (HIV) o sindrome di immunodeficienza acquisita (AIDS)
• Metastasi attive del SNC e metastasi del SNC come uniche lesioni di malattia

E.5 End points

E.5.1

Primary end point(s)

1/ Safety and tolerability of BMS-986205 as measured by incidence of
adverse events (AEs), serious adverse events (SAEs), AEs leading to
discontinuation, deaths, and clinical laboratory test abnormalities.
2/ Safety of BMS-986205 plus nivolumab as measured by incidence of
adverse events (AEs), serious adverse events (SAEs), AEs leading to
discontinuation, deaths, and clinical laboratory test abnormalities.
3/ Safety of BMS-986205 plus both nivolumab and ipilimumab as
measured by incidence of adverse events (AEs), serious adverse events
(SAEs), AEs leading to discontinuation, deaths, and clinical laboratory
test abnormalities.
4/ Anti-tumor activity of BMS 986205 administered in combination iwth
nivolumab as measured by the best overall response (BOR), duration of
response (DOR), and progression-free survival rates (PFSRs) at multiple
time points
5/ Anti-tumor activity of BMS 986205 administered in combination withboth nivolumab and ipilimumab as measured by the best overall
response (BOR), duration of response (DOR), and progression-free
survival rates (PFSRs) at multiple time points

1- Valutazione della sicurezza e tollerabilità di BMS-986205 effettuata sulla base dell’incidenza degli eventi avversi, seri e non seri, delle reazioni avverse che hanno condotto alla discontinuazione del farmaco, dei decessi e delle anomalie di laboratorio.

2- Valutazione della sicurezza di BMS-986205 in combinazione con nivolumab effettuata sulla base dell’incidenza degli eventi avversi, seri e non seri, delle reazioni avverse che hanno condotto alla discontinuazione del farmaco, dei decessi e delle anomalie di laboratorio.

3- Valutazione della sicurezza di BMS-986205 in combinazione con nivolumab ed ipilimumab effettuata sulla base dell’incidenza degli eventi avversi, seri e non seri, delle reazioni avverse che hanno condotto alla discontinuazione del farmaco, dei decessi e delle anomalie di laboratorio.

4- Attività antitumorale di BMS-986205 somministrato in combinazione con nivolumab sulla base dei risultati ottenuti in termini di BOR, DOR e PFSRs a diverse tempistiche.

5- Attività antitumorale di BMS-986205 somministrato in combinazione con nivolumab ed ipilimumab sulla base dei risultati ottenuti in termini di BOR, DOR e PFSRs a diverse tempistiche.

E.5.1.1

Timepoint(s) of evaluation of this end point

1/ [Time Frame: 100 days after the last dose of study therapy]
2/ [Time Frame: 100 days after the last dose of study therapy]
3/ [Time Frame: 100 days after the last dose of study therapy]
4/ [Time Frame: Approximately 3 years]
5/ [Time Frame: Approximately 3 years]

1- 100 giorni dopo l'ultima dose del farmaco in studio
2- 100 giorni dopo l'ultima dose del farmaco in studio
3- 100 giorni dopo l'ultima dose del farmaco in studio
4- circa 3 anni
5- circa 3 anni

E.5.2

Secondary end point(s)

1. Maximum observed plasma concentration (Cmax) of BMS-986205
2. Time of maximum observed plasma concentration (Tmax) of BMS-986205
3. Area under the concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of BMS-986205
4. Area under the concentration-time curve from time zero to the time of the last quantifiable concentration [AUC(0-T)] of BMS-986205
5. Area under the concentration-time curve in 1 dosing interval [AUC(TAU)] of BMS-986205
6. Trough observed plasma concentration at the end of the dosing interval (Ctrough) of BMS-986205
7. Observed plasma concentration at 24 hours (C24) of BMS-986205
8. Apparent terminal phase half-life (T-HALF) of BMS-986205
9. Apparent total body clearance (CLT/F) of BMS-986205
10. Apparent renal clearance (CLR/F) of BMS-986205
11. Volume of distribution of terminal phase (Vz/F) of BMS-986205
12. Apparent volume of distribution at steady state (Vss/F) of BMS-986205
13. Accumulation index (AI) of BMS-986205
14. Percent urinary recovery (%UR) of BMS-986205
15. Percent urinary recovery over 24 hours(%UR24) of BMS-986205
16. Ratio of metabolite Cmax to parent Cmax, corrected for molecular weight (MR_Cmax) of BMS-986205
17. Ratio of metabolite AUC(0-T) to parent AUC(0-T), corrected for molecular weight (single dose in clinical pharmacology substudy only)
[MR_AUC(0-T)] of BMS-986205
18. Ratio of metabolite AUC(TAU) to parent AUC(TAU), corrected for molecular weight [MR_AUC(TAU)] of BMS-986205
19. Ratio of metabolite AUC(INF) to parent AUC(INF), corrected for molecular weight (single dose in clinical pharmacology substudy only)
[MR_AUC(INF)] of BMS-986205
20. Anti-drug antibody (ADA) response to Nivolumab in combination with BMS-986205
21. Objective response rate (ORR)
22. Progression free survival rate (PFSR)
23. Duration of response(DOR); A/ To characterize the PK and PD of BMS-986205 administered alone, in
combination with nivolumab, and in combination with both nivolumab
and ipilimumab.
1. Maximum observed plasma concentration (Cmax) of BMS-986205
[Time Frame: Approximately 3 years]
2. Time of maximum observed plasma concentration (Tmax) of BMS-
986205 [Time Frame: Approximately 3 years]
3. Area under the concentration-time curve from time zero extrapolated
to infinite time [AUC(INF)] of BMS-986205 [Time Frame: Approximately
3 years]
4. Area under the concentration-time curve from time zero to the time
of the last quantifiable concentration [AUC(0-T)] of BMS-986205 [Time
Frame: Approximately 3 years]
5. Area under the concentration-time curve in 1 dosing interval
[AUC(TAU)] of BMS-986205 [Time Frame: Approximately 3 years]
6. Trough observed plasma concentration at the end of the dosing
interval (Ctrough) of BMS-986205 [Time Frame: Approximately 3
years]
7. Observed plasma concentration at 24 hours (C24) of BMS-986205
[Time Frame: Approximately 3 years]
8. Apparent terminal phase half-life (T-HALF) of BMS-986205 [Time
Frame: Approximately 3 years]
9. Apparent total body clearance (CLT/F) of BMS-986205 [Time
Frame: Approximately 3 years]
10. Apparent renal clearance (CLR/F) of BMS-986205 [Time Frame:
Approximately 3 years]
11. Volume of distribution of terminal phase (Vz/F) of BMS-986205
[Time Frame: Approximately 3 years]
12. Apparent volume of distribution at steady state (Vss/F) of BMS-
986205 [Time Frame: Approximately 3 years]
13. Accumulation index (AI) of BMS-986205 [Time Frame:
Approximately 3 years]
14. Percent urinary recovery (%UR) of BMS-986205 [Time Frame:
Approximately 3 years]
15. Percent urinary recovery over 24 hours(%UR24) of BMS-986205
[Time Frame: Approximately 3 years]
16. Ratio of metabolite Cmax to parent Cmax, corrected for molecular
weight (MR_Cmax) of BMS-986205 [Time Frame: Approximately 3
years]
17. Ratio of metabolite AUC(0-T) to parent AUC(0-T), corrected for
molecular weight (single dose in clinical pharmacology substudy only)
[MR_AUC(0-T)] of BMS-986205 [Time Frame: Approximately 3 years]
18. Ratio of metabolite AUC(TAU) to parent AUC(TAU), corrected for
molecular weight [MR_AUC(TAU)] of BMS-986205 [Time Frame:
Approximately 3 years]
19. Ratio of metabolite AUC(INF) to parent AUC(INF), corrected for
molecular weight (single dose in clinical pharmacology substudy only)
[MR_AUC(INF)] of BMS-986205 [Time Frame: Approximately 3 years]
20. Anti-drug antibody (ADA) response to Nivolumab in combination
with BMS-986205 [Time Frame: Approximately 3 years]
B/ To characterize the immunogenicity of nivolumab when administered
in combination with BMS-986205 and in combination with both BMS-
986205 and ipilimumab.
C/ To characterize the immunogenicity of ipilimumab when administered
in combination with nivolumab and BMS-986205

1. Concentrazione plasmatica massima osservata (Cmax) di BMS-986205
2. Tempo della concentrazione plasmatica massima osservata (Tmax) di BMS-986205
3. Area sotto la curva concentrazione-tempo dal tempo zero estrapolata al tempo infinito [AUC(INF)] di BMS-986205
4. Area sotto la curva concentrazione-tempo dal tempo zero al tempo dell’ultima concentrazione quantificabile [AUC(0-T)] di BMS-986205
5. Area sotto la curva concentrazione-tempo in un intervallo di dosaggio [AUC(TAU)] di BMS-986205
6. Concentrazione minima plasmatica osservata alla fine dell’intervallo di dosaggio (Ctrough) di BMS-986205
7. Concentrazione plasmatica osservata a 24 ore (C24) di BMS-986205
8. Emivita apparente della fase terminale (T-HALF) di BMS-986205
9. Clearance totale apparente (CLT/F) di BMS-986205
10. Clearance renale apparente (CLR/F) di BMS-986205
11. Volume di distribuzione della fase terminale (Vz/F) of BMS-986205
12. Volume apparente di distribuzione allo steady state (Vss/F) di BMS-986205
13. Indice di accumulo (AI) di BMS-986205
14. Percentuale di recupero nelle urine (%UR) di BMS-986205
15. Percentuale di recupero nelle urine nelle 24 ore (%UR24) di BMS-986205
16. Rapporto tra Cmax del metabolita e Cmax del prodotto parente, corretto per il peso molecolare (MR_Cmax) di BMS-986205
17. Rapporto tra AUC(0-T) del metabolita e AUC(0-T) del prodotto parente, corretto per il peso molecolare (a singola dose solo nel sottostudio di clinical pharmacology) [MR_AUC(0-T)] di BMS-986205
18. Rapporto tra AUC(TAU) del metabolita e AUC(TAU) del prodotto parente, corretto per il peso molecolare [MR_AUC(TAU)] di BMS-986205
19. Rapporto tra AUC(INF) del metabolita e AUC(INF) del prodotto parente, corretto per il peso molecolare (a singola dose solo nel sottostudio di clinical pharmacology)[MR_AUC(INF)] di BMS-986205
20. Risposta anti-drug antibody (ADA) al Nivolumab in combinazione con BMS-986205
21. Percentuale di Risposta Obiettiva (ORR)
22. Percentuale di Sopravvivenza Libera da Progressione (PFSR)
23. Durata della Risposta (DOR)
; A/ Caratterizzare la PK e la PD di BMS-986205 somministrato da solo, in combinazione con nivolumab, e in combinazione con nivolumab ed ipilimumab

1/ Concentrazione plasmatica massima osservata (Cmax) di BMS-986205
2/ Tempo della concentrazione plasmatica massima osservata (Tmax) di BMS-986205
3/ Area sotto la curva concentrazione-tempo dal tempo zero estrapolata al tempo infinito [AUC(INF)] di BMS-986205
4/ Area sotto la curva concentrazione-tempo dal tempo zero al tempo dell’ultima concentrazione quantificabile [AUC(0-T)] di BMS-986205
5/ Area sotto la curva concentrazione-tempo in un intervallo di dosaggio [AUC(TAU)] di BMS-986205
6/ Concentrazione minima plasmatica osservata alla fine dell’intervallo di dosaggio (Ctrough) di BMS-986205
7/ Concentrazione plasmatica osservata a 24 ore (C24) di BMS-986205
8/ Emivita apparente della fase terminale (T-HALF) di BMS-986205
9/ Clearance totale apparente (CLT/F) di BMS-986205
10/ Clearance renale apparente (CLR/F) di BMS-986205
11/ Volume di distribuzione della fase terminale (Vz/F) of BMS-986205
12/ Volume apparente di distribuzione allo steady state (Vss/F) di BMS-986205
13/ Indice di accumulo (AI) di BMS-986205
14/ Percentuale di recupero nelle urine (%UR) di BMS-986205
15/ Percentuale di recupero nelle urine nelle 24 ore (%UR24) di BMS-986205
16/ Rapporto tra Cmax del metabolita e Cmax del prodotto parente, corretto per il peso molecolare (MR_Cmax) di BMS-986205
17/ Rapporto tra AUC(0-T) del metabolita e AUC(0-T) del prodotto parente, corretto per il peso molecolare (a singola dose solo nel sottostudio di clinical pharmacology) [MR_AUC(0-T)] di BMS-986205
18/ Rapporto tra AUC(TAU) del metabolita e AUC(TAU) del prodotto parente, corretto per il peso molecolare [MR_AUC(TAU)] di BMS-986205
19/ Rapporto tra AUC(INF) del metabolita e AUC(INF) del prodotto parente, corretto per il peso molecolare (a singola dose solo nel sottostudio di clinical pharmacology)[MR_AUC(INF)] di BMS-986205
20/ Risposta anti-drug antibody (ADA) al Nivolumab in combinazione con BMS-986205

B/ caratterizzare l’immunogenicità di nivolumab quando è somministratoin combinazione con BMS-986205 e in combinazione con BMS-986205 ed ipilimumab

C/ caratterizzare l’immunogenicità di ipilimumab quando è somministrato in combinazione con nivolumab e BMS-986205

E.5.2.1

Timepoint(s) of evaluation of this end point

Approximately 3 years; Approximately 3 years

Circa 3 anni; circa 3 anni

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

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

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

United States

France

Germany

Italy

Netherlands

Spain

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

LVLS

L’ultima visita di follow up dell’ultimo paziente

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:

544

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

363

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

450

F.4.2.2

In the whole clinical trial

907

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 BMS supplied 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 BMS.

Alla fine dello studio, i soggetti che continuano a dimostrare un beneficio clinico dal farmaco potrebbero essere idonei per continuare a ricevere la terapia. Il farmaco verrebbe fornito tramite una estensione dello studio, uno studio di rollover che richiederà approvazione dell’autorità competente e del comitato etico o attraverso un meccanismo alternativo a discrezione di BMS.

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

2017-05-04

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-02-21

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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