Clinical Trials Register

Summary
EudraCT Number:	2017-001725-40
Sponsor's Protocol Code Number:	CV202-103
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2018-11-23
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2017-001725-40

A.3

Full title of the trial

A Phase 1b/2 Study of BMS-813160 in Combination with Chemotherapy or Nivolumab in Patients with Advanced Solid Tumors.

Estudio fase 1b/2 de BMS-813160 en combinación con quimioterapia o nivolumab en pacientes con tumores sólidos avanzados

A.3.1

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

A Study of BMS-813160 in Combination with Chemotherapy or Nivolumab in Patients with Advanced Solid Tumors

Un estudio de BMS-813160 en combinación con quimioterapia o nivolumab en pacientes con tumores sólidos avanzados

A.4.1

Sponsor's protocol code number

CV202-103

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	GCT-SU
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	900 150 160
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	CCR2/5
D.3.2	Product code	BMS-813160
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	NA
D.3.9.1	CAS number	1286279-29-5
D.3.9.2	Current sponsor code	BMS-813160
D.3.9.3	Other descriptive name	BMS813160
D.3.9.4	EV Substance Code	SUB118847
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	150
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 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	NIVOLUMAB-100 mg/vial (10 mg/mL)
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, 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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	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-40 mg/vial (10 mg/mL)
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, 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	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: 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.2.5	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
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	GEMCITABINE HYDROCHLORIDE
D.3.9.3	Other descriptive name	GEMCITABINE HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB02324MIG
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 5
D.1.2 and D.1.3	IMP Role	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.2.5	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
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	Fluorouracil
D.3.9.3	Other descriptive name	FLUOROURACIL
D.3.9.4	EV Substance Code	SUB07721MIG
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 6
D.1.2 and D.1.3	IMP Role	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	ABRAXANE
D.2.1.1.2	Name of the Marketing Authorisation holder	Celgene Europe Limited
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	Nab-paclitaxel
D.3.4	Pharmaceutical form	Concentrate for 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	Paclitaxel
D.3.9.3	Other descriptive name	PACLITAXEL ALBUMIN-BOUND
D.3.9.4	EV Substance Code	SUB127678
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	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 7
D.1.2 and D.1.3	IMP Role	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.2.5	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
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	Folinic acid
D.3.9.2	Current sponsor code	Leucovorin
D.3.9.3	Other descriptive name	FOLINIC ACID
D.3.9.4	EV Substance Code	SUB13910MIG
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 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	Yes
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
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	irinotecan hydrochloride, trihydrate
D.3.9.3	Other descriptive name	IRINOTECAN HYDROCHLORIDE TRIHYDRATE
D.3.9.4	EV Substance Code	SUB45873
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Advanced Solid Tumors

tumores sólidos avanzados

E.1.1.1

Medical condition in easily understood language

Advanced Solid Tumors

tumores sólidos avanzados

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10065252
E.1.2	Term	Solid tumor
E.1.2	System Organ Class	100000004864

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10049280
E.1.2	Term	Solid tumour
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:
_To assess the safety and tolerability of BMS-813160 in combination with either FOLFIRI (Arm A), Gem + nabpaclitaxel (Arm B), or nivolumab (Arm C) in participants with advanced CRC or pancreatic cancer.
_To assess the pharmacodynamic effects of BMS-813160 in
tumor samples
PART 2:
_To assess the preliminary efficacy of BMS-813160 in
combination with either FOLFIRI (Arm A), Gem +
nab-paclitaxel or nivolumab + Gem + nab-paclitaxel
(Arm B), or nivolumab (Arm C), and as monotherapy
(Arm D) in participants with advanced CRC or pancreatic
cancer

Parte 1
- Evaluar la seguridad y la tolerabilidad de BMS-813160 en combinación con FOLFIRI (Brazo A), Gem + nab-paclitaxel (Brazo B) o nivolumab (Brazo C) en pacientes con CRC o cáncer de páncreas avanzado
- Evaluar los efectos farmacodinámicos de BMS-813160 en muestras tumorales
Parte 2
- Evaluar la eficacia preliminar de BMS-813160 en combinación con FOLFIRI (Brazo A), Gem + nab-paclitaxel o nivolumab +Gem+ nab-paclitaxel (Brazo B) o nivolumab (Brazo C) y como monoterapia (Brazo D) en pacientes con CRC o cáncer de páncreas
Parte 2

E.2.2

Secondary objectives of the trial

PART 1:
_To assess the preliminary efficacy of BMS-813160 in combination with either FOLFIRI (Arm A), Gem + nabpaclitaxel (Arm B), or nivolumab (Arm C) in participants with advanced CRC or pancreatic cancer
_To characterize the PK of BMS-813160 and its metabolite (BMS-939429) when administered alone, and in combination with either Gem + nab-paclitaxel, FOLFIRI or nivolumab;
_To characterize the immunogenicity of nivolumab when administered in combination with BMS-813160
_
PART 2:
_To assess the safety and tolerability of BMS-813160 in combination with either FOLFIRI (Arm A), Gem + nab-paclitaxel or nivolumab + Gem + nab-paclitaxel (Arm B) , or nivolumab (Arm C), and as monotherapy (Arm D) in participants with advanced CRC or pancreatic cancer;
_To assess the pharmacodynamic effects of BMS-813160 in
tumor samples

 Parte 1
- Evaluar la eficacia preliminar de BMS-813160 en combinación con FOLFIRI (Brazo A), Gem + nab-paclitaxel (Brazo B) o nivolumab (Brazo C) en pacientes con CRC o cáncer de páncreas avanzado

- Caracterizar la FC de BMS-813160 y su metabolito (BMS-939429) cuando se administra en monoterapia y en combinación con Gem + nab-paclitaxel, FOLFIRI o nivolumab
- Caracterizar la inmunogenicidad de nivolumab cuando se administra en combinación con BMS-813160
Parte 2
-Evaluar la seguridad y la tolerabilidad de BMS-813160 en combinación con FOLFIRI (Brazo A), Gem + nab-paclitaxel o nivolumab+Gem + nab-paclitaxel (Brazo B) o nivolumab (Brazo C) y como monoterapia (Brazo D) en pacientes con CRC o cáncer de páncreas avanzado
-Caracterizar los efectos farmacodinámicos de BMS-813160 en muestras tumorales

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Participants must have metastatic colorectal or pancreatic cancer
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤1
- Ability to swallow pills or capsules
- All participants will be required to undergo mandatory pre and on-treatment biopsies
- Adequate marrow function
- Adequate other organ functions
- Ability to comply with study visits, treatment, procedures, PK and PD sample collection, and required study follow-up

-Los pacientes deben tener carcinoma colorrectal o pancreático metastásico.
-Los pacientes deben tener un estado según ECOG de ≤1.
-Los pacientes deben tener capacidad de tragar pastillas o cápsulas
-Todos los pacientes deberán someterse a biopsias obligatorias
pre y en tratamiento
-Adecuada función medular
-Adecuada función de otros órganos
-Capacidad de cumplir con las visitas de estudio, el tratamiento, los procedimientos, PK y PD recogida de muestras, y seguimiento del estudio requerido

E.4

Principal exclusion criteria

- Histology other than adenocarcinoma (neuroendocrine or acinar cell). If mixed tumor, the predominant histology must be adenocarcinoma;
- Suspected, known, or progressive CNS metastases (Imaging required only if participants are symptomatic); Participants with adequately treated CNS metastasis are eligible if the participant’s neurologic function returned to baseline and are not currently on steroids for
at least 2 weeks prior to study entry. Participants with history of brain metastasis require baseline MRI of the brain prior to study entry;
- Participants with active, known or suspected autoimmune disease
- Participants with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study treatment administration except for adrenal replacement steroid doses > 10 mg daily prednisone equivalent in the absence of active autoimmune disease (Treatment with a short course of steroids (< 5 days) up to 7 days prior to initiating study treatment is permitted)
- Interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected treatment-related pulmonary toxicity
- Prior treatment with CCR2 and/or CCR5 inhibitors, PD-1, PD(L)-1 or CTLA-4 antibodies;
- History of allergy to study treatments or any of its components of the study arm that participant is enrolling

-Histología distinta de adenocarcinoma (célula neuroendocrina o acinar).
Si el tumor es mixto, la histología predominante debe ser adenocarcinoma;
- Metástasis del SNC sospechadas, conocidas o progresivas (se requieren imágenes
solo si los pacientes son sintomáticos); Pacientes con metástasis del SNC tratadas adecuadamente son elegibles si la función neurológica del paciente regresó a la línea de base y no están actualmente en tratamiento con esteroides durante al menos 2 semanas antes del ingreso al estudio. Pacientes con historia de
metástasis cerebrales requieren una RM inicial del cerebro antes del ingreso al estudio;
- Pacientes con enfermedad autoinmune activa, conocida o que se sospecha
- Pacientes con una enfermedad que requiere tratamiento sistémico con algún corticoide (> 10 mg diarios equivalentes de prednisona) u otros
medicamentos inmunosupresores dentro de los 14 días de tratamiento de la administración del estudio
a excepción de las dosis de esteroides de reemplazo suprarrenal> 10 mg
equivalente diario de prednisona en ausencia de enfermedad autoinmune activa
(Tratamiento con un ciclo corto de esteroides (<5 días) hasta 7 días antes
para iniciar el tratamiento del estudio está permitido)
- Enfermedad pulmonar intersticial que es sintomática o puede interferir con la
detección o al manejo del tratamiento sospechado relacionada con la toxicidad del tratamiento
- Tratamiento previo con inhibidores CCR2 y/o CCR5, PD-1, PD (L) -1 o
anticuerpos CTLA-4
- Historial de alergia a los tratamientos de estudio o cualquiera de sus componentes del brazo en estudio en el que los pacientes se han inscrito

E.5 End points

E.5.1

Primary end point(s)

-Adverse events (AEs): Measured by incidence of AEs
-Serious adverse events (SAEs): Measured by incidence of SAEs
-AEs meeting protocol-defined dose limiting toxicity criteria: Measured by incidence of AEs that meet the protocol-defined dose limiting toxicity criteria
-AEs leading to discontinuation: Measured by incidence of AEs leading to discontinuation
-Death: Measured by incidence of deaths
-Incidence of laboratory abnormalities: Measured by any laboratory test result that is clinically significant or meets the definition of an SAE, any laboratory test result abnormality that required the patient to have study treatment discontinued or interrupted, or any laboratory test result abnormality that required the participant to
receive specific corrective therapy
-Electrocardiogram (ECG): ECGs will be evaluated by the investigator for any clinically significant changes or for changes meeting dose modifying criteria
-Summary measures of vital signs: Including weight, body temperature, respiratory rate, pulse oximetry, seated blood pressure and heart rate
-Objective response rate (ORR): ORR is defined as the proportion of
all treated participants whose Best overall response (BOR) is either
complete response or partial response. BOR for a participant will be assessed per Response Evaluation Criteria in Solid Tumors (RECIST v1.1 by investigator
-Median duration of response (DOR): DOR for a participant with a BOR of CR or PR, is defined as the time between the date of first response and the date of the first objectively documented tumor progression per RECIST v1.1 or death, whichever occurs first
-Progression free survival (PFS) rate: PFS for a participant is defined as
the time from the first dosing date to the date of first objectively
documented disease progression or death due to any cause, whichever occurs first;
_Decrease in Treg or TAM in tumor samples

-Acontecimientos adversos (AA): medidos por incidencia de eventos adversos
- Acontecimientos adversos graves (AAG): medidos por incidencia de AAG
-Cumple con los criterios de toxicidad que limitan la dosis definidos por el protocolo: Medido por incidencia de AA que cumplen con la toxicidad limitante de la dosis definida por los criterios del protocolo
-Discontinuación de los acontecimientos s adversos (AA): medido por la incidencia de eventos adversos que conducen a
discontinuación
-Muerte: Medido por incidencia de muertes
-Incidencia de anomalías en las pruebas de laboratorio: medidas por cualquier resultado de pruebas de laboratorio que es significativo o cumple con la definición de un acontecimiento adverso grave (AAG), cualquier anomalía en el resultado de la prueba de laboratorio que requirió que el paciente interrumpiera el tratamiento del estudio, o cualquier anomalía en el resultado de las pruebas de laboratorio que requirió que el paciente recibiera tratamiento correctivo específico
-Electrocardiograma (ECG): los ECG serán evaluados por el investigador para
cualquier cambio clínicamente significativo o cambios que cumplan con el criterio de modificación de la dosis
-Mediciones resumen de las constantes vitales: incluyendo peso, temperatura corporal, frecuencia respiratoria, oximetría de pulso, presión arterial y frecuencia cardiaca ajustada
-Reducción de la tasa de respuestas objetivas (TRO): TRO se define como la proporción de todos los pacientes tratados cuya mejor respuesta global (MRG) es cualquier respuesta completa o respuesta parcial. Será evaluado por el investigador el MRG para un paciente según los criterios de evaluación de respuesta en tumores sólidos (RECIST v1.1)
-Duración media de la respuesta (DMR): DMR para un paciente con un MRG de CR o PR, se define como el tiempo entre la fecha de la primera respuesta y la fecha de la primera progresión tumoral objetivamente documentada por
RECIST v1.1 o muerte, lo que ocurra primero
-Tasa de supervivencia libre de progresión (SLP): SLP se define como el tiempo desde la primera fecha de administración hasta la fecha de la primera progresión de la enfermedad documentada o muerte por cualquier causa, cualquiera que ocurra primero
-Disminución de las células T reguladoras (Treg) o de los macrófagos asociados al tumor (TAM) en muestras tumorales

E.5.1.1

Timepoint(s) of evaluation of this end point

-Approximately 4 years for AEs, SAEs, AEs leading to discontinuation, death, Incidence of laboratory abnormalities, ECG, summary measures of vital signs, ORR and DOR.
-Approximately 6 months for AEs meeting protocol-defined dose
limiting toxicity criteria and
-at 24 weeks for PFS.

- Aproximadamente 4 años para acontecimientos adversos (AAs), AAGs, AAs que llevan a la interrupción, muerte, incidencia de anomalías de laboratorio, ECG, mediciones resumen de las constantes vitales , TRO y DMR.
- Aproximadamente 6 meses para los AA que cumplen con la dosis definida por el protocolo limitando el criterio de toxicidad y
-en 24 semanas para SLP

E.5.2

Secondary end point(s)

Maximum observed plasma concentration (Cmax), Time of maximum observed plasma concentration (Tmax), Trough observed plasma
concentration (Ctrough), C24, Area under the concentration-time curve from time 0 to 8 hours postdose [AUC(0-8)], [AUC (24)], Apparent total body clearance (CLT/F), Accumulation index, calculated
based on ratio of AUC(TAU) and Cmax at steady state to after the
first dose (AI), Renal clearance (CLR), Percent urinary recovery over 24
hours corrected for molecular weight (%UR), Ratio of metabolite Cmax to parent Cmax, corrected for molecular (MR_Cmax), [MR_AUC(24)]; Frequency of positive anti-drug antibody (ADA) to nivolumab during combination therapy.

La concentración plasmática máxima observada (Cmax), el tiempo de concentración plasmática máxima observada (Tmax), concentración plasmática mínima observada (Ctrough), C24, área bajo la curva de concentración-tiempo desde tiempo 0 a 8 horas después de la dosis [AUC (0-8)], [AUC (24)], aclaramiento corporal total aparente (CLT / F), índice de acumulación, calculado en base a la relación de AUC (TAU) y Cmax en estado estable después del primera dosis (AI), aclaramiento renal (CLR), porcentaje de recuperación urinaria superior a 24 horas corregidas para el peso molecular (% UR), ratio de Cmax del metabolito para progenitor Cmax, corregido para molecular (MR_Cmax), [MR_AUC (24)]; Frecuencia de anticuerpos antidrogas positivos (ADA) a nivolumab durante el tratamiento de combinación.

E.5.2.1

Timepoint(s) of evaluation of this end point

Approximately 4 years.

Aproximadamente 4 años

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

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

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

PK and PD of BMS-813160

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

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

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

Canada

France

Germany

United States

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

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:

183

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

183

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

117

F.4.2.2

In the whole clinical trial

366

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 or study part, BMS will not continue to provide BMS supplied study treatment to participants/investigators unless BMS chooses to extend the study. The investigator should ensure that the participant receives appropriate standard of care to treat the condition under study.

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2018-12-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-10-22

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2023-06-14

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