Clinical Trials Register

Summary
EudraCT Number:	2020-003655-15
Sponsor's Protocol Code Number:	CA209-67T
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-05-20
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2020-003655-15

A.3

Full title of the trial

A Phase 3, Open-label, Randomized, Noninferiority Trial of Subcutaneous Formulation of Nivolumab Versus Intravenous Nivolumab in Participants With Advanced or Metastatic Clear Cell Renal Cell Carcinoma Who Have Received Prior Systemic Therapy.

Sperimentazione di non inferiorità di Fase 3, in aperto, randomizzata su una formulazione sottocutanea di Nivolumab rispetto a Nivolumab per via endovenosa in partecipanti con carcinoma a cellule renali con componente a cellule chiare avanzato o metastatico che hanno ricevuto una precedente terapia sistemica

A.3.1

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

A Study of Subcutaneous Nivolumab in Previously Treated Advanced or Metastatic Clear Cell Renal Cell Carcinoma

Studio su Nivolumab sottocutaneo in carcinoma a cellule renali con componente a cellule chiare avanzato o metastatico trattato in precedenza

A.3.2

Name or abbreviated title of the trial where available

A Study of Subcutaneous Nivolumab in Previously Treated Advanced or Metastatic Clear Cell Renal Cell

Studio su Nivolumab sottocutaneo in carcinoma a cellule renali con componente a cellule chiare avanz

A.4.1

Sponsor's protocol code number

CA209-67T

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1255-9514

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	GSM-CT
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.5.6	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
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-10 ml vial-COMMERCIAL
D.3.2	Product code	[BMS-936558]
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	NIVOLUMAB
D.3.9.1	CAS number	946414-94-4
D.3.9.2	Current sponsor code	BMS-936558
D.3.9.3	Other descriptive name	BMS936558
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	Nivolumab sottocutaneo coformulato con eccipiente rHuPH20
D.3.2	Product code	[BMS-986298-01]
D.3.4	Pharmaceutical form	Solution for injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous 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	BMS936558
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	120
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

Metastatic Clear Cell Renal Cell Carcinoma

carcinoma a cellule renali con componente a cellule chiare metastatico

E.1.1.1

Medical condition in easily understood language

Kidney Cancer

Cancro al rene

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10050076
E.1.2	Term	Metastatic renal carcinoma
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

To demonstrate PK noninferiority of SC nivolumab vs IV nivolumab administration

Dimostrare la non inferiorità Farmacocinetica (PK) di nivolumab sotto cutaneo (SC) rispetto a nivolumab per infusione endovenosa (EV)

E.2.2

Secondary objectives of the trial

1 To demonstrate the ORR noninferiority of SC nivolumab vs IV nivolumab administration.
2. To evaluate efficacy of SC nivolumab over 12 months.
3. To evaluate PK of SC nivolumab and IV nivolumab administration.
4. To evaluate the safety profile of SC nivolumab and IV nivolumab administration.

1. Dimostrare la non inferiorità ORR di nivolumab in somministrazione SC rispetto a nivolumab in somministrazione EV
2. Valutare l’efficacia della somministrazione SC ed EV di nivolumab in 12 mesi
3. Valutare la PK della somministrazione SC ed EV di nivolumab
4. Valutare il profilo di sicurezza della somministrazione SC ed EV di nivolumab

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Histological confirmation of renal cell carcinoma (RCC)
- Advanced RCC (not amenable to curative surgery or radiation therapy) or metastatic RCC (Stage IV)
- Measurable disease as defined by Response Evaluation Criteria in Solid Tumor
- Received no more than 2 prior systemic treatment regimens
- Progression or intolerance on or after the last treatment regimen received

– Conferma istologica di carcinoma a cellule renali (RCC) con una componente a cellule chiare (RCC)
– RCC avanzato (non sottoponibile a intervento chirurgico curativo o radioterapia) o RCC metastatico (stadio IV) (American Joint Committee on Cancer [AJCC]).
– Malattia misurabile definita secondo i Criteri di valutazione della risposta nei tumori solidi (RECIST)
– Devono aver ricevuto non più di 2 precedenti regimi di trattamento sistemici.
– Devono presentare evidenza di intolleranza o progressione durante o dopo l’ultimo regime di trattamento ricevuto

E.4

Principal exclusion criteria

- Untreated, symptomatic central nervous system (CNS) metastases.
- Prior immunotherapy (medications which are target the immune system) known as PDL1 or CTLA4 or any other medications working similarly
- Concurrent malignancy (present during screening) requiring treatment or history of prior malignancy active within 2 years prior to randomization

– Metastasi sintomatiche del sistema nervoso centrale (SNC) non trattate
– Precedente Immunoterapia (trattamento farmacologico che ha come target il sistema immunitario) nota come PDL1 o CTLA4 o qualsiasi altro farmaco che funziona nello stesso modo
– Malignità concomitante (presente durante lo screening) che richieda trattamento o anamnesi di precedente malignità attiva nei 2 anni precedenti la randomizzazione

E.5 End points

E.5.1

Primary end point(s)

Cmind28

E.5.1.1

Timepoint(s) of evaluation of this end point

Minimum of 06 months

Minimo 6 mesi

E.5.2

Secondary end point(s)

1 - ORR by BICR, with a minimum of 6 months follow-up.
2 - Efficacy parameters (ORR, DCR, DOR, TTR, PFS, OS) with a minimum of 12 months follow-up.
3 - Cavgd28, Cmax1, Tmax, Cavgss, and Cminss.
4 - Incidence of AEs, SAEs, AEs leading to discontinuation, deaths, and laboratory abnormalities.; 1. ORR mediante BICR, con un minimo di 6 mesi di follow-up
2. Parametri di efficacia (ORR, DCR, DOR, TTR, PFS, OS) con un minimo di 12 mesi di follow-up
3. Cavgd28, Cmaxl, Tmax, Cavgss, e Cminss
4. Incidenza di EA, SAE ed EA che portano all’interruzione del trattamento, al decesso e ad anomalie di laboratorio

E.5.2.1

Timepoint(s) of evaluation of this end point

minimum of 06 months for end points 1 and 3 above
minimum of 12 months for end points 2 and 4 above; Minimo 6 mesi per gli endpoints 1 e 3
Minimo 12 mesi per gli endpoints 2 e 4

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

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

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

Brazil

Chile

Mexico

New Zealand

Russian Federation

Turkey

United States

Finland

France

Ireland

Italy

Poland

Portugal

Romania

Spain

Czechia

Argentina

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

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:

275

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

267

F.4.2.2

In the whole clinical trial

458

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, participants who continue to demonstrate clinical benefit will be eligible to receive BMS supplied study treatment for the maximum treatment duration specified in protocol. Study treatment 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.

Al termine dello studio, i partecipanti che continuano a dimostrare un beneficio clinico saranno elegibili a ricevere il trattamento in studio fornito da BMS per la durata massima di trattamento specificata nel protocollo. Il trattamento in studio sarà fornito tramite una estensione dello studio, uno studio rollover che richiederà approvazione dalla relativa autorità competente e dal comitato Etico o tramite un altro meccanismo 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

2021-03-17

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-02-24

P. End of Trial
P.	End of Trial Status	Ongoing

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