Clinical Trials Register

Summary
EudraCT Number:	2017-000367-33
Sponsor's Protocol Code Number:	CA209-9GW
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:	2021-08-02
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

2017-000367-33

A.3

Full title of the trial

Phase 1/2 Study to Evaluate the Safety and Preliminary Efficacy of
Nivolumab Combined with Daratumumab in Participants with Advanced or
Metastatic Solid Tumors

Studio di fase 1/2 per valutare la sicurezza e l¿efficacia preliminare di nivolumab associato a daratumumab in pazienti affetti da tumori solidi avanzati o metastatici

A.3.1

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

The purpose of this study is to determine whether an investigational
combination immuno-therapy of nivolumab and daratumumab is safe and
effective in the treatment of advanced or metastatic solid tumors.

Lo scopo di questo studio ¿ quello di determinare se l¿immunoterapia sperimentale di combinazione dei farmaci nivolumab e daratumumab ¿ sicura ed efficace nel trattamento di tumori solidi avanzati o metastatici

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

CA209-9GW

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

ISRCTN00000000

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT03098550

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1191-9721

A.5.4

Other Identifiers

Name:

ooo

Number:

ooo

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	000
B.5.5	Fax number	000
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	Yes
D.2.1.1.1	Trade name	Opdivo
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.3.4	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.3.9.3	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	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	Yes
D.2.1.1.1	Trade name	DARZALEX
D.2.1.1.2	Name of the Marketing Authorisation holder	Janssen-Cilag International NV
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.3.4	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	DARATUMUMAB
D.3.9.1	CAS number	945721-28-8
D.3.9.2	Current sponsor code	ooo
D.3.9.3	Other descriptive name	ooo
D.3.9.4	EV Substance Code	SUB175772
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	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

Advanced or metastatic solid tumors

Tumori solidi avanzati o metastatici

E.1.1.1

Medical condition in easily understood language

Advanced Cancer

Tumori avanzati

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	PT
E.1.2	Classification code	10061873
E.1.2	Term	Non-small cell lung cancer
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10051971
E.1.2	Term	Pancreatic adenocarcinoma
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10075566
E.1.2	Term	Triple negative breast cancer
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The purpose of this study is to determine whether an investigational
combination immuno-therapy of nivolumab and daratumumab is safe
and effective in the treatment of advanced or metastatic solid tumors.

E.2.2

Secondary objectives of the trial

-To evaluate the objective response rate (ORR) of nivolumab
combined with daratumumab in participants with advanced or
metastatic tumors in each cohort.
- To assess progression free survival (PFS) of nivolumab
combined with daratumumab in participants with advanced or metastatic
tumors in each cohort.
-To characterize the pharmacokinetics of nivolumab and daratumumab in
participants with advanced or metastatic tumors.
-To characterize the immunogenicity of nivolumab and daratumumab in
participants with advanced or metastatic tumors

¿ Valutare il tasso di risposta obiettiva (Objective Response Rate, ORR) di nivolumab associato a daratumumab in pazienti affetti da tumori avanzati o metastatici in ciascuna coorte.

¿ Valutare la sopravvivenza libera da progressione (Progression Free Survival, PFS) di nivolumab associato a daratumumab in pazienti affetti da tumori avanzati o metastatici in ciascuna coorte.

¿ Caratterizzare la farmacocinetica di nivolumab e daratumumab in pazienti affetti da tumori avanzati o metastatici.

¿ Caratterizzare l¿immunogenicit¿ di nivolumab e daratumumab in pazienti affetti da tumori avanzati o metastatici

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: Rev01
Date: 18/04/2017
Title: Phase 1/2 Study to Evaluate the Safety and Preliminary Efficacy of
Nivolumab Combined with Daratumumab in Participants with Advanced or
Metastatic Solid Tumors, see protocol section 9.8.1: Additional Research Collection
Objectives: ooo

Pharmacogenomics
Version: Rev01
Date: 18/04/2017
Title: Phase 1/2 Study to Evaluate the Safety and Preliminary Efficacy of
Nivolumab Combined with Daratumumab in Participants with Advanced or
Metastatic Solid Tumors, see protocol section 9.8.1: Additional Research Collection
Objectives: ooo

Farmacogenetica
Versione: Rev01
Data: 18/04/2017
Titolo: Studio di fase 1/2 per valutare la sicurezza e l¿efficacia preliminare di nivolumab associato a daratumumab in pazienti affetti da tumori solidi avanzati o metastatici,
sezione del protocollo 9.8.1: Additional Research collection

Obiettivi: ooo

Farmacogenomica
Versione: Rev01
Data: 18/04/2017
Titolo: : Studio di fase 1/2 per valutare la sicurezza e l¿efficacia preliminare di nivolumab associato a daratumumab in pazienti affetti da tumori solidi avanzati o metastatici,
sezione del protocollo 9.8.1: Additional Research collection

Obiettivi: ooo

E.3

Principal inclusion criteria

- Patients must have metastatic or advanced solid tumors.
- Women with histologically or cytologically confirmed triple negative breast carcinoma.
- Participants with histologically confirmed pancreatic adenocarcinoma.
- Participants must have histologic or cytologic confirmation of Non
Small Cell Lung Cancer (NSCLC).

• I soggetti partecipanti devono avere tumori solidi metastatici o avanzati.
• Donne con carcinoma mammario triplo negativo, istologicamente o citologicamente confermato.
• Pazienti con adenocarcinoma del pancreas istologicamente confermato.
• I soggetti partecipanti devono avere una conferma istologica o citologica di tumore polmonare non a piccole cellule (NSCLC).

E.4

Principal exclusion criteria

-Active brain metastases or leptomeningeal metastases.
- Any serious or uncontrolled medical disorder.
- Prior malignancy active within the previous 3 years.

• Metastasi cerebrali attive o metastasi leptomeningee.
• Qualsiasi disturbo medico grave o incontrollato.
• Malattie attive precedenti negli ultimi 3 anni

E.5 End points

E.5.1

Primary end point(s)

-Incidence of adverse events (AE)
- Incidence of serious adverse events (SAE)
-Grade of laboratory abnormalities.

1. Incidenza di eventi avversi (Adverse Event, AE);
2. Incidenza di eventi avversi gravi (Serious Adverse Event, SAE);
3. Valori di laboratorio non normali specifici (al grado peggiore).

E.5.1.1

Timepoint(s) of evaluation of this end point

Time Frame: Up to 2.5 years
Time Frame: Up to 2.5 years
Time Frame: Up to 2.5 years

1. Fino a 2,5 anni;
2. Fino a 2,5 anni;
3. Fino a 2,5 anni

E.5.2

Secondary end point(s)

-Objective Response rate (ORR)
¿ Progression Free Survival (PFS)
¿ Anti-Drug Antibodies (ADA) positivity
¿ Area under the concentration-time curve (AUC)
¿ Minimum observed concentration (Cmin)

1. Valutare il tasso di risposta obiettiva (Objective Response Rate, ORR);
2. Valutare la sopravvivenza libera da progressione (Progression Free Survival, PFS);
3. Positivit¿ Anticorpi ADA;
4. Area sotto la curva AUC (concentrazione -tempo);
5. Concentrazione minima osservata (Cmin).

E.5.2.1

Timepoint(s) of evaluation of this end point

-Objective Response rate (ORR) [ Time Frame: Up to 3 years ]
¿ Progression Free Survival (PFS) [ Time Frame: Up to 3 years ]
¿ Anti-Drug Antibodies (ADA) positivity [ Time Frame: Up to 2.5 years ]
¿ Area under the concentration-time curve (AUC) [ Time Frame: Up to
2.5 years ]
¿ Minimum observed concentration (Cmin) [ Time Frame: Up to 2.5 years
]

1. Fino a 3 anni;
2. Fino a 3 anni;
3. Fino a 2,5 anni;
4. Fino a 2,5 anni;
5. Fino a 2,5 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

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Biomarker Assessments, Outcomes Research
Assessments,Immunogenicity Assessments

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

Phase I/II

Fase I/II

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

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

Spain

Switzerland

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

End of trial is defined as the last visit or scheduled procedure shown in
the Schedule of Activities for the last participant.

Definizione della conclusione della sperimentazione, nel caso non sia l'ultima visita dell'ultimo soggetto

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:

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

160

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,BMS will not continue to provide BMS supplied study
treatment unless BMS chooses to extend the study.The Inv should
ensure that the participant receives appropriate SOC to treat the
condition.BMS reserves the right to terminate access to treatment if
a)the study is ended due to safety concerns b)the dev of nivo or dara is
terminated for other reasons c)the participant can obtain medication
from a gov sponsored or private health program.In all cases BMS will
follow local regulations.

Alla fine dello studio, BMS non continuer¿ a fornire i farmaci in studio, a meno che BMS scelga di estendere lo studio. Lo sperimentatore di ciascun centro dovr¿ assicurarsi che i pazienti partecipanti ricevano lo Standard of Care appropriato per trattare la loro malattia. BMS si riserva il diritto di interrompere l'accesso al trattamento se a) lo studio ¿ terminato a causa di problemi di sicurezza b) lo sviluppo clinico di nivolumab o di daratumumab ¿ terminato per altri motivi c) il paziente p

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

2017-07-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-07-13

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

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