Clinical Trials Register

Summary
EudraCT Number:	2017-003581-27
Sponsor's Protocol Code Number:	CA209-9UT
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2018-05-21
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

Spain - AEMPS

A.2

EudraCT number

2017-003581-27

A.3

Full title of the trial

A Phase 2, Randomized, Open-label Study of Nivolumab or Nivolumab/BMS-986205 Alone or Combined with Intravesical BCG in Participants with BCG-Unresponsive, High-Risk, Non-Muscle Invasive Bladder Cancer

Estudio fase 2, aleatorizado, abierto, de nivolumab o nivolumab/ BMS-986305 solos o en combinación con BCG intravesical, en pacientes con cáncer de vejiga sin invasión muscular, de alto riesgo, sin respuesta a BCG (CA209-9UT)

A.3.1

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

A Phase 2 Study of Nivolumab or Nivolumab/BMS-986205 Alone or Combined with Intravesical BCG in Participants with Bladder Cancer

Estudio fase 2 de nivolumab, o nivolumab/BMS-986205 solos o en combinación con BCG intravesical en participantes con cáncer de vejiga

A.3.2

Name or abbreviated title of the trial where available

CheckMate 9UT: CHECKpoint pathway and nivoluMAb clinical Trial Evaluation 9UT

CheckMate 9UT: Vía Checkpoint y evaluación en ensayo clínico 9UT de nivolumab)

A.4.1

Sponsor's protocol code number

CA209-9UT

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1201-4325

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	+ 900 150 160
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
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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 - 4ml vial
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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	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	IDO-1 inhibitor - 100mg
D.3.2	Product code	BMS-986205
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	BMS-986205
D.3.9.2	Current sponsor code	BMS-986205-04
D.3.9.3	Other descriptive name	BMS986205
D.3.9.4	EV Substance Code	SUB179973
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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	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	IDO-1 inhibitor - 50mg
D.3.2	Product code	BMS-986205
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	BMS-986205
D.3.9.2	Current sponsor code	BMS-986205-04
D.3.9.3	Other descriptive name	BMS986205
D.3.9.4	EV Substance Code	SUB179973
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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	Tice-BCG
D.2.1.1.2	Name of the Marketing Authorisation holder	N.V. Organon
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	TICE BCG
D.3.4	Pharmaceutical form	Intravesical solution/solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravesical use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	TICE BCG
D.3.9.3	Other descriptive name	BCG (BACILLUS CALMETTE-GUÉRIN) BACTERIA
D.3.9.4	EV Substance Code	SUB20565
D.3.10	Strength
D.3.10.1	Concentration unit	U unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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	Yes
D.3.11.13.1	Other medicinal product type	TICE® BCG for intravesical use, is an attenuated, live culture preparation of the Bacillus of Calmette and Guerin (BCG) strain of Mycobacterium bovis

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

BCG-Unresponsive, High-Risk, Non-Muscle Invasive Bladder Cancer

Cáncer de vejiga sin invasión muscular, de alto riesgo, sin respuesta a BCG

E.1.1.1

Medical condition in easily understood language

Bladder Cancer

Cáncer de vejiga sin invasión muscular, de alto riesgo, sin respuesta a BCG

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	20.0
E.1.2	Level	PT
E.1.2	Classification code	10005005
E.1.2	Term	Bladder cancer recurrent
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

-) To estimate complete response (CR) rate, per pathology review committee (PRC), and its duration in carcinoma in situ (CIS) participants.

-) To determine Event Free Survival (EFS), per PRC, for all non-CIS participants (high-grade papillary Ta or any T1).

- Estimar la tasa de respuesta completa (TRC) según el comité (CRAP) y su duración en participantes con carcinoma in situ (CIS)

- Determinar la supervivencia libre de acontecimientos (SLA) según el comité (CRAP) en todos los pacientes sin carcinoma in situ (CIS) (Ta papilar de alto grado o cualquier T1).

E.2.2

Secondary objectives of the trial

-) To evaluate progression free survival (PFS), per PRC, for all participants (high grade papillary Ta, any T1, and/or CIS).

-) To describe the safety and tolerability of nivolumab and nivolumab + BMS-986205, alone or in combination with intravesical BCG.

Evaluar la supervivencia libre de progresión (SLP), según el CRAP, en todos los pacientes (Ta papilar de alto grado, cualquier T1 y/o CIS).

Describir la seguridad y tolerabilidad de nivolumab y nivolumab + BMS-986205, solos o en combinación con BCG intravesical.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

-) Pathologically demonstrated BCG-unresponsive*, high-risk NMIBC defined as carcinoma in situ (CIS) with or without papillary component, any T1, or Ta high-grade lesions; diagnosis required within 8 weeks (56 days) prior to starting treatment and must be confirmed by the Pathology Review Committee (PRC).
-)Predominant histologic component (> 50%) must be urothelial (transitional cell) carcinoma
-) Must have undergone each of the following procedures within 8 weeks (56 days) of randomization:
a) Complete excision of all papillary disease (T1/TaHG). For participants with T1 lesions, a re-staging TURBT must be performed within 4 weeks after the initial TURBT to ensure that the pathology specimen contains muscularis propria that is free of invasive
tumor per PRC.
b) Resection or fulguration of all detectable CIS, if feasible. Fluorescence-guided cystoscopy is encouraged but not mandated. It is understood that due to the nature of this disease, complete resection of CIS cannot be assured.
c) Random sampling of bladder mucosa for detection of occult CIS. The bladder must be mapped by visual inspection and random biopsies taken from the trigone, right and left lateral walls, posterior wall, dome and prostatic urethra. In addition, the presence of
any suspicious lesions must be recorded and these lesions will be biopsied.
d) Urine cytology must be obtained by bladder wash. Recognizing the possibility of occult CIS, cytology at screening does not need to be negative for study participation.
e) Computed tomography (CT) scan of the chest and CT or magnetic resonance imaging (MRI) of the abdomen and pelvis and all other areas of suspected disease to exclude locally advanced or metastatic bladder cancer or synchronous UC in the upper urinary tracts within 90 days prior to randomization
f) Participants should either be deemed medically unfit for radical cystectomy, or should have refused radical cystectomy after consultation with their urologist or oncologist. Participants may be deemed medically unfit for radical cystectomy due to comorbid conditions with a risk of mortality from radical cystectomy ≥ 5% as estimated by the American College of Surgeons risk calculator using the current procedure terminology code 51595 or 51596 for cystectomy

CVSIM de alto riesgo, demostrado histológicamente, sin respuesta a BCG*, definido como carcinoma in situ (CIS) con o sin componente papilar, cualquier T1 o lesiones Ta de alto grado; es necesario que diagnóstico haya sido dentro del plazo de 8 semanas (56 días) antes de comenzar el tratamiento y debe ser confirmado por el Comité de Revisión de Anatomía Patológica (CRAP).

El componente histológico predominante (> 50%) debe ser carcinoma urotelial (de células transicionales)

Cada uno de los siguientes procedimientos deben haberse realizado dentro de las 8 semanas (56 días) previas a la aleatorización:

♦ Escisión completa de toda la enfermedad papilar (T1/TaAG). En pacientes con lesiones T1, debe realizarse una RTUTV dentro de las 4 semanas después de la RTUTV inicial para asegurar que la muestra de anatomía patológica contiene muscular propia libre de tumor invasivo según el CRAP.
♦ Resección o fulguración de todo el CIS detectable, si es factible. Se insta a la cistoscopia guiada por fluorescencia, pero no es obligatoria. Se entiende que, debido a la naturaleza de esta enfermedad, no puede asegurarse la resección completa del CIS.
♦ Muestreo aleatorio de mucosa vesical para la detección de CIS oculto. La vejiga debe cartografiarse mediante inspección visual y biopsias aleatorias extraídas del trígono, las paredes laterales derecha e izquierda, la pared posterior, la cúpula y la uretra prostática (en participantes varones). Además, debe registrarse la presencia de cualquier lesión sospechosa y estas lesiones deben biopsiarse.
♦Debe obtenerse citología de orina mediante lavado vesical. Admitiendo la posibilidad de CIS oculto, la citología en la selección no tiene que ser negativa para la participación en el estudio.
♦ Estudio de tomografía computarizada (TC) del tórax y TC o resonancia magnética (RM) del abdomen y la pelvis y todas las demás zonas de sospecha de la enfermedad para descartar cáncer de vejiga localmente avanzado o metastásico o CU sincrónico en las vías urinarias superiores dentro de los 90 días previos a la aleatorización
♦ Los pacientes deben ser médicamente no aptos para cistectomía radical o deben haber rechazado la cistectomía radical después de consultar con su urólogo u oncólogo. Los pacientes pueden considerarse médicamente no aptos para una cistectomía radical debido a condiciones comórbidas con riesgo de mortalidad por cistectomía radical ≥ 5% según lo estimado por la calculadora de riesgos del American College of Surgeons usando el actual procedimiento de terminología código 51595 o 51596 para cistectomía.

E.4

Principal exclusion criteria

-) Women who are pregnant or breastfeeding
-) Participants with a personal or family (ie, in a first-degree relative) history of cytochrome b5 reductase deficiency (previously called methemoglobin reductase deficiency) or other diseases
that put them at risk of methemoglobinemia.
-) Participants with a history of glucose-6-phosphate dehydrogenase deficiency or other congenital or autoimmune hemolytic disorders.
-) Evidence of locally advanced or metastatic bladder cancer as seen in cross-sectional imaging of the chest, abdomen, and pelvis
-) UC in the upper genitourinary tract (kidneys, renal collecting systems, ureters) within 24 months of enrollment
-) UC and/or CIS in the prostatic urethra within 12 months of enrollment
-) Locally advanced disease demonstrated by pelvic examination preferably performed under anesthesia
-) Previous or concurrent muscle invasive or disseminated/metastatic bladder cancer
-) Prior treatment with an anti-PD-1, anti-programmed death ligand 1 (PD-L1), anti-PD-L2, or anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
-) Prior treatment with BMS-986205 or any other IDO1 inhibitors
-) Prior systemic chemotherapy or immunotherapy. Intravesical chemotherapy and/or interferon administered prior to the date of tumor sample submission is permitted.
-) Prior radiation therapy for bladder cancer
-) Prior surgery for bladder cancer other than TURBT and/or bladder biopsies

• Mujeres embarazadas o en la lactancia
• Pacientes con antecedentes personales o familiares (esto es, en un familiar de primer grado) de déficit de citocromo b5 reductasa (llamado previamente déficit de metahemoglobina reductasa) u otras enfermedades que les causen un riesgo de metahemoglobinemia.
• Pacientes con antecedentes de déficit de glucosa-6-fosfato deshidrogenasa (G6PD) u otros trastornos hemolíticos congénitos o autoinmunitarios.
• Pruebas de cáncer de vejiga localmente avanzado o metastásico visto en pruebas de imagen transversales de tórax, abdomen y pelvis
• CU en las vías genitourinarias superiores (riñones, sistemas colectores renales, uréteres) dentro de los 24 meses previos al reclutamiento
• CU y/o CIS de la uretra prostática dentro de los 12 meses previos al reclutamiento
• Enfermedad localmente avanzada demostrada por exploración pélvica, realizada preferiblemente bajo anestesia
• Cáncer de vejiga con invasión muscular o diseminado/metastásico previo o concurrente
• Tratamiento previo con un anticuerpo anti-PD-1, anti-ligando de muerte programada 1 (PD-L1), anti-PD-L2 o anti-proteína asociada al linfocito T citotóxico 4 (anti-CTLA-4) o cualquier otro anticuerpo o fármaco que se dirija específicamente a las vías de coestimulación de los linfocitos T o del punto de control
• Tratamiento previo con BMS-986205 o cualquier otro inhibidor de IDO1
• Quimioterapia sistémica o inmunoterapia previas. Se permite la quimioterapia intravesical y/o el interferón administrado antes de la fecha del envío de la muestra tumoral.
• Radioterapia previa para cáncer de vejiga

E.5 End points

E.5.1

Primary end point(s)

-) Proportion of carcinoma in situ participants with Complete response, per PRC.
-) Duration of Complete response (duration of complete response), per PRC, in carcinoma in situ participants with Complete response.
-) event-free survival, per PRC, for all non-carcinoma in situ participants.

Proporción de participantes carcinoma in situ con respuesta completa según el CRAP

Duración de la respuesta completa (DdRC) según el CRAP, en pacientes con carcinoma in situ con respuesta completa

Supervivencia libre de acontecimientos según el CRAP, para todos los pacientes sin carcinoma in situ

E.5.1.1

Timepoint(s) of evaluation of this end point

The complete response (CR) rate will be estimated at 6 and 12 months.

The overall CR rate will also be estimated as above.

Event free survival rate will be reported at 3, 6, 9, 12, 18 and 24 months.

La tasa de Respuesta completa (RC) se calculará a los 6 y a los 12 meses

La tasa global de Respuesta completa (RC) también se calculará como un valor superior

La tasa de supervivencia libre de acontecimientos se informará a los 3, 6, 9, 12, 18 y 24 meses

E.5.2

Secondary end point(s)

-) progression-free survival, per PRC, for all participants
-) Overall safety and tolerability will be measured by the incidence of AEs, SAEs, AEs leading to discontinuation, immunemediated AEs, deaths, and laboratory abnormalities and changes from baseline.

Supervivencia libre de progresión, según CRAP, para todos los pacientes

Se medirá la seguridad y tolerancia global por la incidencia de efectos adversos (EAs), efectos adversos graves (EAGs) que lleven a la discontinuación, EAinmunorrelacionados, muertes, y anormalidades de laboratorio y cambios respecto al momento basal.

E.5.2.1

Timepoint(s) of evaluation of this end point

Progression-free survival rate at 3, 6, 9, 12, 18 and 24 months will be provided.
There are no specified time points for safety. Plan is to file with CR at 12 months and then with EFS at 18 months. Safety will be reported as well.

Se proporcionará la Tasa de supervivencia libre de progresión a los 3, 6, 9, 12, 18 y 24 meses.

No hay puntos de tiempo especificados para la seguridad. El plan es presentar con respuesta completa (RC) a los 12 meses y luego con supervivencia libre de efectos (SLE) a los 18 meses. La seguridad será informada también.

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

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)

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

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)

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

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

Argentina

Australia

Brazil

Canada

Chile

China

France

Italy

Mexico

Netherlands

Russian Federation

Spain

Turkey

United Kingdom

United States

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:

144

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

336

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

100

F.4.2.2

In the whole clinical trial

480

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)

See protocol Section 7.8. At the end of the study, BMS will not continue to provide BMS supplied study treatment to
participants/investigators beyond maximum treatment duration of 104 weeks unless BMS chooses
to extend the study. The investigator should ensure that the participant receives appropriate
standard of care to treat the condition under study.

Ver la sección 7.8 del protocolo. Al final del estudio, BMS no continuará proporcionando
el tratamiento del estudio suministrado por BMS a pacientes / investigadores más allá de la duración máxima de tratamiento de 104 semanas, a menos que BMS elija extender el estudio. El investigador debe asegurarse de que el paciente recibe el standard of care apropiado para tratar la enfermedad que ampara el estudio.

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

2018-08-08

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-07-10

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2022-08-22

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