Clinical Trials Register

Summary
EudraCT Number:	2022-000294-67
Sponsor's Protocol Code Number:	CA209-6L6
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2022-11-18
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

2022-000294-67

A.3

Full title of the trial

A Phase II Study of Adjuvant Nivolumab Switch from Intravenous (IV) to Subcutaneous (SC) Use in Participants with Resected Stage III or Stage IV Melanoma or High Risk Invasive Urothelial Carcinoma Originating in the Bladder

Studio di fase II sul passaggio di Nivolumab adiuvante dall'uso endovenoso (EV) a quello sottocutaneo (SC) in partecipanti con melanoma resecato di stadio III o IV o carcinoma uroteliale invasivo ad alto rischio con origine nella vescica.

A.3.1

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

A Study of Nivolumab IV to Subcutaneous Switch in Adjuvant Melanoma and Bladder Cancer

Studio sul passaggio di Nivolumab da EV a sottocutaneo nel melanoma e nel tumore della vescica in fase adiuvante

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

CA209-6L6

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1273-4725

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.5.4	Telephone number	0034914565300
B.5.5	Fax number	00000000
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 sottocutaneo coformulato con eccipiente rHuPH20
D.3.2	Product code	[BMS-986298-01]
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	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	BMS-986298
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	150
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	Yes
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	Comparator
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 (100mg/10ml)
D.2.1.1.2	Name of the Marketing Authorisation holder	Bristol-Myers Squibb Pharma EEIG
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Nivolumab - flaconcino da 10 ml - COMMERCIALE
D.3.2	Product code	[BMS-936558]
D.3.4	Pharmaceutical form	Concentrate for solution for injection/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.3.9.4	EV Substance Code	SUB32944
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Stage III A/B/C/D, Stage IV melanoma or Muscle-Invasive Urothelial Carcinoma

Melanoma allo stadio III A/B/C/D, stadio IV o xarcinoma uroteliale muscolo-invasivo

E.1.1.1

Medical condition in easily understood language

Melanoma and Bladder Cancer

Melanoma e Cancro alla Vescica

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	10053571
E.1.2	Term	Melanoma
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	10064467
E.1.2	Term	Urothelial 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 evaluate participants' preference upon switching from Nivo IV to Nivo SC

Valutare la preferenza dei partecipanti al passaggio da Nivo endovenoso (EV) a Nivo SC

E.2.2

Secondary objectives of the trial

To assess the safety and tolerability of Nivo SC and Nivo IV
To evaluate participants' preference for Nivo SC after the switch period

Valutare la sicurezza e la tollerabilità di Nivo SC e Nivo EV
Valutare la preferenza dei partecipanti per Nivo SC dopo il periodo di transizione

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Eligible for adjuvant therapy for melanoma or muscle-invasive urothelial carcinoma originating from the bladder
• Melanoma: resected Stage IIIA/B/C/D or Stage IV (AJCC 8th edition)
• Bladder: pT3-pT4a or pN+ ineligible or refusal of adjuvant cisplatin chemotherapy OR ypT2-pT4a or ypN+ who received neo-adjuvant cisplatin chemotherapy
• ECOG performance status 0-1; =18

- Idoneità alla terapia adiuvante per melanoma o carcinoma uroteliale muscolo-invasivo originante dalla vescica
• Melanoma: stadio IIIA/B/C/D o stadio IV resecato (secondo l’8¿ edizione della classificazione dell’American Joint Committee on Cancer [AJCC])
• Vescica: pT3-pT4a o pN+ non idoneo alla chemioterapia adiuvante con cisplatino o rifiuto della stessa OPPURE ypT2-pT4a o ypN+ precedentemente sottoposto a chemioterapia neo-adiuvante con cisplatino
- Stato di validità dell’Eastern Cooperative Oncology Group (gruppo orientale cooperativo di oncologia) 0-1; =18

E.4

Principal exclusion criteria

• Ocular or mucosal melanoma
• Upper tract urothelial carcinoma (ureter, renal pelvis), NMIBC
• Untreated/unresected CNS or leptomeningeal metastases
• Prior treatment with immuno-oncology agents

• Melanoma oculare o mucosale
• Carcinoma uroteliale del tratto superiore (uretere, pelvi renale), tumore della vescica non muscolo-invasivo (Non Muscle Invasive Bladder Cancer, [NMIBC])
• Metastasi del sistema nervoso centrale (SNC) o leptomeningee non trattate/non resecate
• Precedente trattamento con agenti immuno-oncologici

E.5 End points

E.5.1

Primary end point(s)

Proportion of participants that prefer Nivo SC at the first assessment of patient preference using PEPQ (Question 1)

Percentuale di partecipanti che preferiscono Nivo SC alla prima valutazione della preferenza del paziente utilizzando il PEPQ (Patient Experience and Preference Questionnaire, [Questionario sull’esperienza e sulla preferenza del paziente]) (Domanda 1)

E.5.1.1

Timepoint(s) of evaluation of this end point

After the first assessment of patient experience and preference questionnaire

Dopo la prima valutazione del questionario sull’esperienza e sulla preferenza del paziente

E.5.2

Secondary end point(s)

-Incidence of all AEs, SAEs, treatment-related AEs including IMAEs, AEs & SAEs leading to discontinuation or death
-Proportion of participants that prefer Nivo SC at the second patient preference assessment using PEPQ (Question 1)

- Incidenza di tutti gli EA, eventi avversi seri (Serious Adverse Event, [SAE]), EA correlati al trattamento, compresi eventi avversi immuno-mediati (Immune-Mediated Adverse Event, [IMAE]), EA e SAE che portano all’interruzione o al decesso
- Percentuale di partecipanti che preferiscono Nivo SC alla seconda valutazione della preferenza del paziente utilizzando il PEPQ (Domanda 1)

E.5.2.1

Timepoint(s) of evaluation of this end point

- Throughout the treatment period, lasting from start of Nivo IV until 100 days following discontinuation of Nivo dosing
- After the second assessment of the patient experience and preference questionnaire

- Per tutta la durata del periodo di trattamento, dall’inizio di Nivo EV fino a 100 giorni dopo l’interruzione della somministrazione di Nivo
- Dopo la seconda valutazione del questionario sull’esperienza e sulla preferenza del paziente

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

E.6.7

Pharmacodynamic

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

Yes

E.6.13.1

Other scope of the trial description

To evaluate participants' preference for Nivo SC after the switch period

Valutare la preferenza dei partecipanti per Nivo SC dopo il periodo di transizione

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)

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

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

United States

Spain

Germany

Italy

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 participant last visit or completion of Survival Follow-up Visit.
Study completion is defined as the final date on which last participant has completed the end of trial visit (last visit or Survival Follow-up Visit).

La fine della sperimentazione è definita come l’ultima visita dell’ultimo partecipante o il completamento della visita di follow-up della sopravvivenza.
Il completamento dello studio è definito come la data finale in cui l’ultimo partecipante ha completato la visita di fine sperimentazione (ultima visita o visita di follow-up della sopravvivenza).

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

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)

None

Nessuno

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

2022-12-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-11-09

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2023-03-20

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