Clinical Trials Register

Summary
EudraCT Number:	2020-001863-10
Sponsor's Protocol Code Number:	CA001-050
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2021-06-08
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

2020-001863-10

A.3

Full title of the trial

A Randomized, Open Label Phase II Clinical Trial of BMS-986012 in Combination with Carboplatin, Etoposide and Nivolumab as First-line Therapy in Extensive-Stage Small Cell Lung Cancer

Sperimentazione clinica di fase 2, randomizzata, in aperto, su BMS 986012, in associazione con carboplatino, etoposide e nivolumab come terapia di prima linea nel carcinoma polmonare a piccole cellule in stadio esteso

A.3.1

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

A Study of BMS-986012 in Combination with Carboplatin, Etoposide, and Nivolumab as First-line Therapy in Extensive-stage Small Cell Lung Cancer

Studio randomizzato su BMS-986012 in combinazione con carboplatino, etoposide e nivolumab in partecipanti con carcinoma polmonare a piccole cellule in stadio esteso

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

CA001-050

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1250-4427

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	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-fucosyl-GM1
D.3.2	Product code	[BMS-986012]
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	anti-fucosyl-GM1
D.3.9.2	Current sponsor code	BMS-986012
D.3.9.3	Other descriptive name	BMS986012
D.3.9.4	EV Substance Code	SUB168020
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	30
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	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.3.9.3	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: 3
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	CARBO-cell® 10 mg/ml, concentrate for solution for infusion
D.2.1.1.2	Name of the Marketing Authorisation holder	STADAPHARM GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Carboplatin
D.3.2	Product code	[-]
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	CARBOPLATINO
D.3.9.1	CAS number	41575-94-4
D.3.9.2	Current sponsor code	-
D.3.9.3	Other descriptive name	CARBOPLATIN
D.3.9.4	EV Substance Code	SUB06614MIG
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	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	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	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: 4
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	Carboplatin Bendalis 10 mg/ml, concentrate for solution for infusion
D.2.1.1.2	Name of the Marketing Authorisation holder	Bendalis GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Carboplatin
D.3.2	Product code	[-]
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	CARBOPLATINO
D.3.9.1	CAS number	41575-94-4
D.3.9.2	Current sponsor code	-
D.3.9.3	Other descriptive name	CARBOPLATIN
D.3.9.4	EV Substance Code	SUB06614MIG
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	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	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	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	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	ETO-cell® 20 mg/ml concentrate for solution for infusion
D.2.1.1.2	Name of the Marketing Authorisation holder	STADAPHARM GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	etoposide
D.3.2	Product code	[-]
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	ETOPOSIDE
D.3.9.1	CAS number	33419-42-0
D.3.9.2	Current sponsor code	-
D.3.9.3	Other descriptive name	ETOPOSIDE
D.3.9.4	EV Substance Code	SUB07337MIG
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	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	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	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

Extensive-stage Small Cell Lung Cancer

Carcinoma polmonare a piccole cellule in stadio avanzato

E.1.1.1

Medical condition in easily understood language

Lung Cancer

Carcinoma polmonare

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	10041068
E.1.2	Term	Small cell lung cancer extensive stage
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

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

- To assess the safety and tolerability for participants randomized to BMS-986012 in combination with carboplatin, etoposide, and nivolumab for 4 cycles (induction) followed by BMS-986012 and nivolumab maintenance (Arm A) vs those randomized to carboplatin, etoposide, and nivolumab for 4 cycles (induction) followed by nivolumab maintenance (Arm B).

- To compare the PFS as assessed by BICR of participants treated in the combination induction and maintenance therapies of Arms A and B described above.

- Valutare la sicurezza e la tollerabilità per i partecipanti randomizzati con
BMS-986012 in combinazione con carboplatino, etoposide e nivolumab
per 4 cicli (induzione) seguito da BMS-986012 e nivolumab in
mantenimento (Braccio A) rispetto a quelli randomizzati con carboplatino, etoposide e nivolumab per 4 cicli (induzione) seguito da mantenimento con nivolumab (Braccio B).
- confrontare la PFS valutata dal BICR dei partecipanti trattati nel
terapie combinate di induzione e mantenimento dei bracci A e B
descritto sopra.

E.2.2

Secondary objectives of the trial

- To estimate the PFSR at 6 and 12 months in each treatment arm, based on PFS by RECIST v1.1 as assessed by BICR.
- To compare PFS as assessed by investigator of participants treated in the combination induction and maintenance therapies of Arms A and B described above.
- To estimate the PFSR at 6 and 12 months in each treatment arm based on PFS by RECIST v1.1 assessed by investigator.
- To estimate the ORR, TTR, and DOR by RECIST v1.1 criteria by BICR and by investigator.
- To assess OS of Arm A and Arm B and estimate OSR at 12 and 24 months by treatment arm.
- To assess associations of fuc-GM1 expression in pretreatment tumor biopsies assessed using IHC and mass spectrometry assays with anti-tumor activity measures.
- To assess associations of PD-L1 expression (CPS) in pretreatment tumor biopsies with anti-tumor activity measures.
- To characterize the immunogenicity of BMS-986012 in combination with carboplatin, etoposide, and nivolumab in Arm A.

- stimare la PFSR a 6 e 12 mesi in ciascun braccio di trattamento, in base
alla PFS da RECIST v1.1 come valutato da BICR.
- confrontare la PFS valutata dallo sperimentatore dei partecipanti trattati con terapie combinate di induzione e mantenimento dei bracci A e B.
- Stimare la PFSR a 6 e 12 mesi in ciascun braccio di trattamento
sulla PFS secondo RECIST v1.1 valutata dallo sperimentatore.
- stimare ORR, TTR e DOR in base ai criteri RECIST v1.1 come valutato da BICR
e dall'investigatore.
- valutare la OS dei bracci A e B e stimare l'OSR a 12 e 24
mesi per braccio di trattamento.
PER ULTERIORI DETTAGLI VEDERE IL PROTOCOLLO

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: Initial
Date: 02/09/2020
Title: A Randomized, Open-label Phase 2 Clinical Trial of BMS-986012 in Combination with Carboplatin, Etoposide, and Nivolumab as First-line Therapy in Extensive-stage Small Cell Lung Cancer- Section 9.8.4
Objectives: Additional research is optional for all study participants, except where retention and/or collection is prohibited by local laws or regulations, ethics committees, or institutional requirements. This collection for additional research is intended to expand the translational R&D capability at Bristol-Myers Squibb, and will support as yet undefined research aims that will advance our understanding of disease and options for treatment. It may also be used to support health authority requests for analysis, and advancement of pharmacodiagnostic development to better target drugs to the right patients. This may also include genetic/genomic exploration aimed at exploring disease pathways, progression and response to treatment etc. Sez 9.8.4

Pharmacogenomics
Version: Initial
Date: 02/09/2020
Title: A Randomized, Open-label Phase 2 Clinical Trial of BMS-986012 in Combination with Carboplatin, Etoposide, and Nivolumab as First-line Therapy in Extensive-stage Small Cell Lung Cancer- Section 9.8.4
Objectives: Additional research is optional for all study participants, except where retention and/or collection is prohibited by local laws or regulations, ethics committees, or institutional requirements. This collection for additional research is intended to expand the translational R&D capability at Bristol-Myers Squibb, and will support as yet undefined research aims that will advance our understanding of disease and options for treatment. It may also be used to support health authority requests for analysis, and advancement of pharmacodiagnostic development to better target drugs to the right patients. This may also include genetic/genomic exploration aimed at exploring disease pathways, progression and response to treatment etc.-Sez 9.8.4

Farmacogenetica
Versione: Initial
Data: 02/09/2020
Titolo: Sperimentazione clinica di fase 2, randomizzata, in aperto, su BMS 986012, in associazione con carboplatino, etoposide e nivolumab come terapia di prima linea nel carcinoma polmonare a piccole cellule in stadio esteso- Sez 9.8.4
Obiettivi: L’Additional research è opzionale per tutti i partecipanti allo studio, tranne nel caso in cui la conservazione e / o la raccolta è vietata dalle leggi o dai regolamenti locali,comitati etici o da requisiti istituzionali. Questa raccolta per ulteriori ricerche ha lo scopo di espandere la capacità di ricerca e l’ R&D traslazionale presso Bristol-Myers Squibb e sarà di supporto per scopi di ricerca ancora indefiniti che faranno avanzare la nostra comprensione della malattia e le eventuali opzioni per il trattamento. Può anche essere usato a supporto delle richieste dell'Autorità Competente per l'analisi e lo sviluppo della farmacodiagnostica allo scopo di indirizzare i farmaci target ai pazienti giusti. Questo può includere anche l'esplorazione genetica / genomica volta a esplorare la pathway della malattia, la progressione e la risposta al trattamento ecc.Sez 9.8.4

Farmacogenomica
Versione: Initial
Data: 02/09/2020
Titolo: Sperimentazione clinica di fase 2, randomizzata, in aperto, su BMS 986012, in associazione con carboplatino, etoposide e nivolumab come terapia di prima linea nel carcinoma polmonare a piccole cellule in stadio esteso- Sez 9.8.4
Obiettivi: L’Additional research è opzionale per tutti i partecipanti allo studio, tranne nel caso in cui la conservazione e / o la raccolta è vietata dalle leggi o dai regolamenti locali,comitati etici o da requisiti istituzionali. Questa raccolta per ulteriori ricerche ha lo scopo di espandere la capacità di ricerca e l’ R&D traslazionale presso Bristol-Myers Squibb e sarà di supporto per scopi di ricerca ancora indefiniti che faranno avanzare la nostra comprensione della malattia e le eventuali opzioni per il trattamento. Può anche essere usato a supporto delle richieste dell'Autorità Competente per l'analisi e lo sviluppo della farmacodiagnostica allo scopo di indirizzare i farmaci target ai pazienti giusti. Questo può includere anche l'esplorazione genetica / genomica volta a esplorare la pathway della malattia, la progressione e la risposta al trattamento ecc- Sez 9.8.4

E.3

Principal inclusion criteria

- Histologically or cytologically documented extensive-stage small cell lung cancer (ES-SCLC) and extensive-stage disease (American Joint Committee on Cancer, 7th edition, Stage IV [T any, N any, M1a, or M1b], or T3-4 due to multiple lung nodules that are too extensive or tumor or nodal volume that is too large to be encompassed in a tolerable radiation plan)
- Must provide a fresh tumor biopsy from the primary disease site (when possible) or from any metastatic site when the primary site is not available
- Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1
- At least 1 measurable lesion by computed tomography (CT) or magnetic resonance imaging (MRI) per Response Evaluation Criteria in Solid Tumors version 1.1 (Response Evaluation Criteria in Solid Tumors (RECIST) v1.1) criteria
- Adequate hematologic and end organ function
- Must agree to follow specific methods of contraception, if applicable

- cancro ai polmoni a Piccole cellule in stadio esteso documentate istologicamente o citologicamente(ES-SCLC) e malattia in stadio esteso (American Joint Committee on Cancer, 7th edition, Stage IV [T any, N any, M1a, or M1b], o T3-4 a causa di più noduli polmonari troppo estesi o tumore o volume nodale troppo grande per essere compreso in un piano di radiazione tollerabile)
- è necessario fornire una nuova biopsia del tumore dal sito della malattia primaria (quando possibile) o da qualsiasi sito metastatico quando il sito primario non è disponibile
- Performance status dell'Eastern Cooperative Oncology Group (ECOG PS) 0 o 1
- Almeno una lesione misurabile mediante tomografia computerizzata (TC) o Risonanza magnetica per immagini (MRI) secondo i criteri di valutazione della risposta in Solid Tumors versione 1.1 (Response Evaluation Criteria in Solid Tumors (RECIST) v1.1)
- Adeguata funzionalità ematologica e degli organi terminali
- È necessario accettare di seguire metodi contraccettivi specifici, se applicabile

E.4

Principal exclusion criteria

- Women who are pregnant or breastfeeding
- Prior chemotherapy, radiation therapy, or biologic therapy for small cell lung cancer (SCLC) for first-line treatment
- Symptomatic brain or other central nervous system (CNS) metastases
- Paraneoplastic autoimmune syndrome requiring systemic treatment
- History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, idiopathic pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest CT scan
- Grade = 2 peripheral sensory neuropathy at study entry
- Significant uncontrolled cardiovascular disease
- Active, known or suspected autoimmune disease or inflammatory disorder

- Donne in gravidanza o in allattamento
- Precedente chemioterapia, radioterapia o terapia biologica per cancro al polmone a piccole cellule(SCLC) per il trattamento di prima linea
- Metastasi sintomatiche al cervello o di altre metastasi del sistema nervoso centrale (SNC)
- Sindrome autoimmune paraneoplastica che richiede un trattamento sistemico
- Storia di fibrosi polmonare idiopatica, polmonite indotta da farmaci,
polmonite idiopatica, polmonite in sviluppo o evidenza di una
polmonite attiva allo screening TC del torace
- Neuropatia sensoriale periferica di grado = 2 all'ingresso nello studio
- Malattia cardiovascolare significativa non controllata
- Malattia autoimmune o infiammatoria attiva, nota o sospetta

E.5 End points

E.5.1

Primary end point(s)

1. Incidence of adverse events (AEs)
2. Incidence of serious adverse events (SAEs)
3. Incidence of AEs leading to discontinuation
4. Incidence of deaths
5. Progression-free survival (PFS) by blinded independent central review (BICR) based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria

1. Incidenza di eventi avversi (EA)
2. Incidenza di eventi avversi gravi (SAE)
3. Incidenza di eventi avversi che portano alla sospensione
4. Incidenza dei decessi
5. Sopravvivenza libera da progressione (PFS) mediante revisione centrale indipendente in cieco (BICR) basato sui criteri di valutazione della risposta nei tumori solidi (RECIST)
v1.1 criteri

E.5.1.1

Timepoint(s) of evaluation of this end point

1: Up to 2 years and 100 days
2-4: Up to 2 years and 128 days
5: Up to 2 years

1: fino a 2 anni e 100 giorni
2-4: fino a 2 anni e 128 giorni
5: fino a 2 anni

E.5.2

Secondary end point(s)

1. Progression-free survival rate (PFSR) [PFS by BICR based on RECIST v1.1 criteria]
2. PFS by investigator based on RECIST v1.1 criteria
3. PFSR [PFS by investigator based on RECIST v1.1 criteria]
4. Objective response rate (ORR) based on RECIST v1.1 criteria
5. Time to response (TTR) based on RECIST v1.1 criteria
6. Duration of response (DOR) based on RECIST v1.1 criteria
7. Overall survival (OS)
8. Overall survival rate (OSR)
9. Measures of tumor fucosyl-GM1 (fuc-GM1) expression by immunohistochemistry (IHC)
10. Measures of tumor fucosyl-GM1 (fuc-GM1) expression association with measures of anti-tumor activity measures (eg, ORR, PFS) (IHC)
11. Measures of tumor fucosyl-GM1 (fuc-GM1) expression by targeted mass spectrometry
12. Measures of tumor fucosyl-GM1 (fuc-GM1) expression association with measures of anti-tumor activity measures (eg, ORR, PFS) (targeted mass spectrometry)
13. Measures of tumor programmed cell death-ligand 1 (PD-L1) expression combined positive score (CPS) at baseline
14. Measures of tumor programmed cell death-ligand 1 (PD-L1) expression association with measures of anti-tumor activity (eg, ORR, PFS)
15. Immunogenicity of BMS-986012 measured by assessment of the presence of specific anti-drug antibodies (ADAs) to BMS-986012 (i.e. incidence of positive ADAs)

1. Tasso di sopravvivenza libera da progressione (PFSR) [PFS da BICR basato su RECIST criteri v1.1]
2. PFS da parte dello sperimentatore in base ai criteri RECIST v1.1
3. PFSR [PFS da parte dello sperimentatore in base ai criteri RECIST v1.1]
4. Tasso di risposta obiettiva (ORR) basato sui criteri RECIST v1.1
5. Tempo alla risposta (TTR) basato sui criteri RECIST v1.1
6. Durata della risposta (DOR) basata sui criteri RECIST v1.1
7. Sopravvivenza globale (OS)
8. Tasso di sopravvivenza globale (OSR)
9. Misure dell'espressione tumorale di fucosil-GM1 (fuc-GM1) mediante
immunoistochimica (IHC)
10. Misure dell’ espressione tumorale fucosil-GM1 (fuc-GM1) associata
con l’ attività antitumorale (p. es., ORR, PFS) (IHC)
11. Misure di espressione tumorale di fucosil-GM1 (fuc-GM1) con
spettrometria di massa
12. Misure dell’ espressione tumorale fucosil-GM1 (fuc-GM1) associata
con l’attività antitumorale (p. es., ORR, PFS) (identificate con spettrometria di massa)
13. Misure dell’espressione della morte cellulare programmata per tumore-ligando 1 (PD-L1) combinato con score positivo e (CPS) al basale
14. Misure dell’espressione della morte cellulare programmata per tumore-ligando 1 (PD-L1) associata con la misura dell’attività antitumorale (p. es., ORR,
PFS)
15. Immunogenicità di BMS-986012 misurata mediante valutazione del
presenza di anticorpi anti-farmaco specifici (ADA) contro BMS-986012 (es.
incidenza di ADA positivi)

E.5.2.1

Timepoint(s) of evaluation of this end point

1, 3: 6 and 12 months
2, 4-6, 9-15: Up to 2 years
7, 8: Up to 3 years

1, 3: 6 e 12 mesi
2, 4-6, 9-15: fino a 2 anni
7, 8: fino a 3 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

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

Yes

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)

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

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

Australia

Canada

Japan

United States

Belgium

France

Germany

Greece

Italy

Netherlands

Poland

Romania

Spain

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

End of trial is defined as the last visit or scheduled procedure for the last participant.

La conclusione della sperimentazione è definita come l'ultima visita o procedura programmata per l’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:

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

Yes

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Subjects/participants unable to give their written consent (eg, stroke or subjects/participants with or severe dementia) may only be enrolled in the study with the consent of a legally acceptable representative. See Appendix 2 of the protocol.

I Soggetti / partecipanti incapaci di dare il loro consenso scritto (ad esempio a causa di un ictus o demenza grave) possono essere arruolati nello studio solo con il consenso di un rappresentante legale riconosciuto.
Vedere l'appendice 2 del protoco

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

120

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 maximum treatment duration as specified in Section 7.1 of the 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.
See protocol section 7.8 for more details.

A conclusione dello studio, i partecipanti che continuano a
dimostrare il beneficio clinico, saranno idonei a ricevere la fornitura BMS
del trattamento in studio per la durata massima del trattamento come specificato in Sezione 7.1 del protocollo. Il trattamento in studio sarà fornito tramite una estensione dello studio oppure tramite uno studio di rollover che richiederà l'approvazione dell’ autorità competente e del 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

2021-06-01

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-05-18

P. End of Trial
P.	End of Trial Status	Trial now transitioned

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Orphan Designation Number:
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