Clinical Trials Register

Summary
EudraCT Number:	2021-004284-27
Sponsor's Protocol Code Number:	CA043-001
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:	2021-12-02
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

2021-004284-27

A.3

Full title of the trial

A Phase 1/2 First-in-human Study of BMS-986288 Alone and in Combination with Nivolumab in Advanced Malignant Tumors

Studio di Fase 1/2, condotto per la prima volta sull’uomo, di BMS-986288 in monoterapia e in combinazione con nivolumab in tumori maligni in stadio avanzato

A.3.1

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

An Investigational Immunotherapy Study of BMS-986288 Alone and in Combination With Nivolumab in Advanced Solid Cancers

Studio sperimentale immuno-terapico di BMS-986288 somministrato in monoterapia e in combinazione con nivolumab in tumori solidi avanzati

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

CA043-001

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1247-3650

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	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	Yes
D.2.1.1.1	Trade name	Opdivo (100 mg/10 ml)
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 - 10ml vial- COMMERCIAL
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.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	anti-CTLA-4 NF Probody mAb
D.3.2	Product code	[BMS-986288]
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.3.9.2	Current sponsor code	BMS-986288
D.3.9.4	EV Substance Code	SUB238165
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	40
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 solid tumors (squamous cell carcinoma of the head and neck (SCCHN), non-small cell lung cancer (NSCLC), cutaneous melanoma, triple-negative breast cancer (TNBC), renal cell carcinoma (RCC), urothelial carcinoma, gastric, esophageal, cervical, and colorectal cancer (CRC).

Tumori solidi in stadio avanzato (carcinoma a cellule squamose della testa e del collo (SCCHN), carcinoma polmonare non a piccole cellule (NSCLC), melanoma cutaneo, carcinoma mammario triplo negativo (TNBC), carcinoma a cellule renali (RCC), carcinoma uroteliale, tumore gastrico, esofageo, della cervice uterina e del colon-retto (CRC).

E.1.1.1

Medical condition in easily understood language

Advanced solid tumors

Tumori solidi 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	21.1
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.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To characterize the safety, tolerability, and Dose-Limiting Toxicities (DLTs) and to determine the Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) of BMS-986288 administered as monotherapy and in combination with nivolumab in participants with select advanced solid tumors

Caratterizzare la sicurezza, la tollerabilità e le tossicità dose-limitanti (DLTs) e determinare la dose massima tollerata (MTD)/ Dose Raccomandata di Fase 2 (RP2D) di BMS-986288 somministrata come monoterapia e in combinazione con nivolumab in partecipanti con tumori solidi in stadio avanzato selezionati

E.2.2

Secondary objectives of the trial

- To characterize the Pharmacokinetic (PK) of BMS-986288 when administered alone and in combination with nivolumab
- To assess the preliminary efficacy of BMS-986288 alone and in combination with nivolumab in advanced solid tumors using RECIST v1.1
- To measure T-regulatory cells (Tregs), and assess Treg change over time and in association with response

-Caratterizzare la farmacocinetica (PK) di BMS-986288 quando somministrato da solo e in combinazione con nivolumab
- Valutare l'efficacia preliminare di BMS-986288 da solo e in combinazione con nivolumab in Tumori solidi in stadio avanzato utilizzando RECIST v1.1
- Misurare le cellule T-regolatrici (Treg) e valutare il cambiamento delle Treg nel tempo e in associazione alla risposta

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Histologic or cytologic confirmation of select solid tumor that is advanced (metastatic, recurrent, and/or unresectable) with measurable disease and have at least 1 lesion accessible for biopsy
- Eastern Cooperative Oncology Group Performance Status of 0 or 1
- Participants must have received, and then progressed, relapsed, or been intolerant to, at least 1 standard treatment regimen in the advanced or metastatic setting according to select solid tumor histologies
Other protocol defined inclusion criteria apply.

-Conferma istologica o citologica di tumore solido selezionato in stadio avanzato (metastatico, ricorrente e/o non resecabile) con malattia misurabile e almeno 1 lesione accessibile per la biopsia
- Eastern Cooperative Oncology Group Performance Status pari a 0 o 1
- I partecipanti devono aver ricevuto, e dopo aver progredito, aver avuto una recidiva o essere risultati intolleranti, almeno un regime di trattamento standard nel setting avanzato o metastatico in accordo alle istologie del tumore solido selezionato.
Si applicano altri criteri di inclusione definiti dal protocollo.

E.4

Principal exclusion criteria

- Participants with active, known or suspected autoimmune disease
- Participants with other active malignancy requiring concurrent intervention
- Participants with primary CNS malignancies or tumors with CNS metastasis as the only site of disease, will be excluded
Other protocol defined exclusion criteria apply.

- Partecipanti con malattia autoimmune attiva, nota o sospetta
- Partecipanti con altri tumori maligni attivi che richiedono un trattamento concomitante
- Partecipanti con neoplasie primarie del SNC o tumori con metastasi del SNC come unico sito di malattia, saranno esclusi

Si applicano altri criteri di esclusione definiti dal protocollo.

E.5 End points

E.5.1

Primary end point(s)

1. Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs), AEs meeting protocol-defined Dose Limiting Toxicities (DLT) Criteria, AEs leading to discontinuation, death and laboratory abnormalities

1. Incidenza di Eventi Avversi (AEs), Eventi Avversi Gravi (SAEs), AEs che corrispondono ai criteri definiti dal protocollo di DLT, AEs che portano all’interruzione del trattamento, decesso, e anomalie di laboratorio

E.5.1.1

Timepoint(s) of evaluation of this end point

1. Up to 2 years

1. Fino a 2 anni

E.5.2

Secondary end point(s)

1. Maximum Observed Concentration (Cmax) of BMS-986288
2. Time of Maximum Observed Concentration (Tmax) of BMS-986288
3. Area Under the Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration AUC(0-T) of BMS-986288
4. Area Under the Concentration-Time Curve in one Dosing Interval AUC(TAU) of BMS-986288
5. Observed Concentration at the end of a Dosing Interval (Ctau) of BMS-986288
6. Trough Observed Concentrations (Ctrough) of BMS-986288
7. Total Body Clearance (CLT) of BMS-986288
8. Average Concentration Over a Dosing Interval at Steady State (Cavgss) of BMS-986288
9. Accumulation Index (AI) of BMS-986288
10. Terminal Half-Life (T-HALF) of BMS-986288
11. Incidence of Anti-Drug Antibodies (ADAs) to BMS-986288
12. Objective Response Rate (ORR) of Participants
13. Duration of Response (DOR) of Participants
14. Progression-Free Survival (PFS) of Participants
15. Time to Response (TTR) of Participants
16 Percentage of change from baseline in T-regulatory cells (Tregs)

1. Concentrazione massima osservata (Cmax) di BMS-986288
2. Tempo di concentrazione massima osservata (Tmax) di BMS-986288
3. Area sotto la curva concentrazione-tempo dal tempo zero al tempo di ultima concentrazione quantificabile AUC(0-T) di BMS-986288
4. Area sotto la curva concentrazione-tempo in un intervallo di dosaggio AUC(TAU) di BMS-986288
5. Concentrazione osservata alla fine di un intervallo di dosaggio (Ctau) di BMS-986288
6. Concentrazioni minime osservate (Ctrough) di BMS-986288
7. Clearance corporea totale (CLT) di BMS-986288
8. Concentrazione media su un intervallo di dosaggio allo stato stazionario (Cavgss) di BMS-986288
9. Indice di accumulo (AI) di BMS-986288
10. Emivita terminale (T-HALF) di BMS-986288
11. Incidenza di anticorpi anti-farmaco (ADA) a BMS-986288
12. Tasso di risposta obiettiva (ORR) dei partecipanti
13. Durata della risposta (DOR) dei partecipanti
14. Sopravvivenza libera da progressione (PFS) dei partecipanti
15. Tempo di risposta (TTR) dei partecipanti
16 Percentuale di variazione rispetto al basale delle cellule T-regolatrici (Treg)

E.5.2.1

Timepoint(s) of evaluation of this end point

1. Up to 2 years
2. Up to 2 years
3. Up to 2 years
4. Up to 2 years
5. Up to 2 years
6. Up to 2 years
7. Up to 4 months
8. Up to 4 months
9. Up to 4 months
10. Up to 4 months
11. Up to 2 years
12. Up to 4 years
13. Up to 4 years
14. Up to 4 years
15. Up to 4 years
16. Up to 2 years

1. Fino a 2 anni
2. Fino a 2 anni
3. Fino a 2 anni
4. Fino a 2 anni
5. Fino a 2 anni
6. Fino a 2 anni
7. Fino 4 mesi
8. Fino 4 mesi
9. Fino 4 mesi
10. Fino 4 mesi
11. Fino a 2 anni
12. Fino a 4 anni
13. Fino a 4 anni
14. Fino a 4 anni
15. Fino a 4 anni
16. Fino a 2 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

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

Yes

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

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

Chile

Argentina

Canada

Italy

Spain

United States

France

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

The end of the study for the trial is defined as the last visit or scheduled procedure shown in the Schedule of Activities (see Protocol Section 2) for the last participant.

La conclusione della sperimentazione è definita come l'ultima visita o procedura programmata riportata nella Schedule of Activities (vedi Sezione 2 del Protocollo) dell'ultimo partecipante

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:

160

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

In situations where consent cannot be given by subjects/participants, their legally acceptable representatives (per country guidelines) are clearly and fully informed about the purpose, potential risks, and other critical issues regarding the study.

Nelle circostanze in cui il consenso non può essere dato dai soggetti/partecipanti, i loro rappresentanti legali (come da linee guida del paese) vengono informati in modo chiaro e completo sullo scopo, i potenziali rischi e altre questioni critiche d

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

200

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 up to a maximum duration of 2 years. 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.

Alla fine dello studio, i partecipanti che continuano a dimostare di avere un beneficio clinico saranno eleggibili a ricevere il trattamento in studio fornito da BMS fino a un massimo di 2 anni. Il trattamento sarà fornito tramite estensione dello studio, tramite uno studio di rollover che richiederà l’approvazione delle autorità sanitarie competenti e dei comitati etici oppure attraverso 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

2022-03-17

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-02-16

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

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IMP with orphan designation in the indication
Orphan Designation Number:
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