Clinical Trials Register

Summary
EudraCT Number:	2015-005806-12
Sponsor's Protocol Code Number:	CBLZ945X2101
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:	2016-08-05
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2015-005806-12

A.3

Full title of the trial

A phase I/II, open-label, multi-center study of the safety and efficacy of BLZ945 as single agent and in combination with PDR001 in adults patients with advanced solid tumors

Estudio fase I/II, abierto, multicéntrico, que evalúa la seguridad y eficacia de BLZ945 en monoterapia y en combinación con PDR001, en pacientes adultos con tumores sólidos avanzados

A.3.1

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

A safety and efficacy study of BLZ945 as single agent and in combination with PDR001 in adults patients with advanced solid tumors

Estudio fase I/II de BLZ945 en monoterapia o de BLZ945 en combinación con PDR001 en tumores sólidos avanzados

A.4.1

Sponsor's protocol code number

CBLZ945X2101

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	Novartis Farmaceútica S.A.
B.1.3.4	Country	Spain
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	Novartis Pharma AG
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novartis Farmaceútica S.A.
B.5.2	Functional name of contact point	Departamento Médico Oncología
B.5.3	Address:
B.5.3.1	Street Address	Gran Via de les Corts Catalanes, 764
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08013
B.5.3.4	Country	Spain
B.5.4	Telephone number	+34 93 3064464
B.5.5	Fax number	+34 93 3064615
B.5.6	E-mail	eecc.novartis@novartis.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.3.2	Product code	BLZ945
D.3.4	Pharmaceutical form	Capsule, hard
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	Not established
D.3.9.1	CAS number	Unavailable
D.3.9.2	Current sponsor code	BLZ945
D.3.9.3	Other descriptive name	BLZ945
D.3.9.4	EV Substance Code	SUB182305
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: 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.3.2	Product code	BLZ945
D.3.4	Pharmaceutical form	Capsule, hard
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	Not established
D.3.9.1	CAS number	Unavailable
D.3.9.3	Other descriptive name	BLZ945
D.3.9.4	EV Substance Code	SUB182305
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	200
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: 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.3.2	Product code	PDR001
D.3.4	Pharmaceutical form	Lyophilisate 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	Not established
D.3.9.1	CAS number	Unavailable
D.3.9.2	Current sponsor code	PDR001
D.3.9.3	Other descriptive name	PDR001
D.3.9.4	EV Substance Code	SUB171710
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	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.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

Tumores sólidos avanzados

E.1.1.1

Medical condition in easily understood language

advanced solid tumors

Tumores sólidos avanzados

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	19.0
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

Phase I: To characterize the safety and tolerability of BLZ945 as a single agent and in combination with PDR001 and to identify the Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D).
Phase II: To assess the anti-tumor activity of BLZ945 in combination with PDR001 (and as single agent if appropriate) in patients with advanced solid tumors.

Fase I: Caracterizar la seguridad y la tolerabilidad de BLZ945 en monoterapia y en combinación con PDR001 e identificar la dosis máxima tolerada (DMT)/dosis recomendada para la fase 2 (DRF2).
Fase II: Evaluar la actividad antitumoral de BLZ945 en combinación con PDR001 (y en monoterapia, si procede), en pacientes con tumores sólidos avanzados.

E.2.2

Secondary objectives of the trial

Phase I: To characterize the pharmacodynamics effect of BLZ945 as a single agent and in combination with PDR001. To characterize PK of BLZ945 as a single agent and in combination with PDR001. To assess the preliminary anti-tumor activity of BLZ945 as single agent and in combination with PDR001.
Phase I and II: To assess emergence of anti-PDR001 antibodies when BLZ945 is administered in combination with PDR001.

Fase I: Caracterizar el efecto farmacodinámico de BLZ945 en monoterapia y en combinación con PDR001. Caracterizar la PK de BLZ945 en monoterapia y en combinación con PDR001. Evaluar la actividad antitumoral preliminar de BLZ945 en monoterapia y en combinación con PDR001.
Fase I y II: Evaluar la aparición de anticuerpos anti-PDR001 cuando BLZ945 se administra en combinación con PDR001.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Phase I: Patients with advanced/metastatic solid tumors, with measurable or unmeasurable disease as determined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 who have progressed despite standard therapy or are intolerant of standard therapy, or for whom no standard therapy exists.
2. Phase I: Patients must have a site of disease amenable to biopsy, and be a candidate for tumor biopsy according to the treating institution’s guidelines. Patient must be willing to undergo a new tumor biopsy at screening, and during treatment.
3. Phase II: Patients with advanced/metastatic tumors in the below selected indications, with at least one measurable lesion as determined by RECIST v1.1 or Response Assessment in Neuro-Oncology Criteria RANO (glioblastoma) advanced pancreatic cancer who failed to respond to standard treatment or progressed on or after treatment with gemcitabine advanced triple negative breast cancer, who failed to respond to standard treatment or progressed on or after standard treatment recurrent glioblastoma who failed to respond or progressed on radiotherapy and temozolomide except for patients with O6- methylguanine-DNA methyltransferase (MGMT) unmethylated newly diagnosed gliobastoma who may have received radiation therapy only.
Other protocol-defined inclusion criteria may apply

1. Fase I: Pacientes con tumores sólidos avanzados/metastásicos, con enfermedad medible o no medible, determinado con los criterios de evaluación de la respuesta en tumores sólidos (RECIST), versión 1.1, que hayan progresado a pesar de la terapia estándar, que no toleren la terapia estándar o para los que no exista terapia estándar.
2. Fase I: Los pacientes deberán presentar una zona de enfermedad susceptible a biopsia y ser aptos para biopsia de tumor de acuerdo con las pautas del centro que lo trate. Los pacientes deberán acceder a que se les realice una biopsia de tumor nueva en la selección y durante el tratamiento.
3. Fase II: Pacientes con tumores metastásico/avanzados en las siguientes indicaciones seleccionadas, con por lo menos una lesión medible, determinado con los RECIST v1.1 o con los criterios de evaluación de la respuesta en neurooncología (RANO) (glioblastoma).
- cáncer de páncreas avanzado que no ha respondido al tratamiento estándar o que ha progresado en o después del tratamiento con gemcitabina
- cáncer de mama triple negativo avanzado, que no ha respondido al tratamiento estándar o que ha progresado en o después del tratamiento estándar
- glioblastoma recurrente que no ha respondido o que ha progresado con radioterapia y temozolomida, excepto para pacientes con glioblastoma de diagnóstico reciente no metilado O6-metilguanida-ADN metiltransferasa (MGMT), que únicamente pueden haber recibido radioterapia

E.4

Principal exclusion criteria

1. History of severe hypersensitivity reactions to monoclonal antibodies.
2. Impaired cardiac function or clinically significant cardiac disease, including any of the following: Clinically significant and/or uncontrolled heart disease such as congestive heart failure requiring treatment (NYHA grade ≥ 2), uncontrolled hypertension or clinically significant arrhythmia QTcF >470 msec on screening electrocardiogram (ECG) or congenital long QT syndrome Acute myocardial infarction or unstable angina pectoris < 3 months prior to study entry
3. Active autoimmune disease or a documented history of autoimmune disease, including ulcerative colitis and Crohn’s disease or any condition that requires systemic steroids, except vitiligo or resolved asthma/atopy that is treated with broncho-dilators (e.g. albuterol). Patients previously exposed to anti-PD-1/PD-L1 treatment who are adequately treated for skin rash or with replacement therapy for endocrinopathies should not be excluded.
4. Systemic steroid therapy or any immunosuppressive therapy (≥10mg/day prednisone or equivalent). Topical, inhaled, nasal and ophthalmic steroids are not prohibited.
5. Use of any vaccines against infectious diseases (e.g. varicella, pneumococcus) within 4 weeks of initiation of study treatment.
6. Patient who received the following therapies: Systemic anti-cancer therapy within 2 weeks of the first dose of study treatment. For cytotoxic agents that have major delayed toxicity, e.g. mitomycin C and nitrosoureas, 4 weeks is indicated as washout period. Pre-treatment with anti-CTLA-4 antibodies in combination with any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathway. Patients pre-treated with anti-CTLA-4 as single agent must have minimum 8 weeks washout period between the last dose of anti-CTLA-4 and the first dose of PDR001.
Participation in an interventional, investigational non-immunotherapy study within 2 weeks of the first dose of study treatment Major surgery within 2 weeks of the first dose of study treatment (mediastinoscopy, insertion of a central venous access device, and insertion of a feeding tube are not considered major surgery).
Use of hematopoietic colony-stimulating growth factors (e.g. G-CSF, GM-CSF, M-CSF) and thrombopoietin mimetics ≤2 weeks prior to start of study drug. An erythroid stimulating agent is allowed as long as it was initiated at least 2 weeks prior to the first dose of study treatment and the patient is on a stable dose.
Radiotherapy within 2 weeks of the first dose of study drug, except for palliative radiotherapy to a limited field, such as for the treatment of bone pain or a focally painful tumor mass. To allow evaluation for response to treatment, patients enrolled in the phase II part must have remaining measurable disease that has not been irradiated.
7. Patient receiving treatment with medications that either strong inducers or inhibitors of CYP2C8 or CYP3A4/5, or patients receiving medication that prohibits proton pump inhibitors and that cannot be discontinued at least 1 week prior to start of treatment and for the duration of the study
8. Known human immunodeficiency virus (HIV), active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection. Patients whose HBV or HCV infection is controlled by antiviral therapy should not be excluded.
Other protocol-defined exclusion criteria may apply.

1. Antecedentes de reacciones de hipersensibilidad severa a anticuerpos monoclonales.
2. Deterioro de la función cardíaca o enfermedad cardíaca clínicamente significativa, incluyendo algo de lo siguiente:
. Enfermedad cardíaca incontrolada y/o clínicamente significativa como insuficiencia cardíaca congestiva que precise tratamiento (grado ≥ 2 de la NYHA), hipertensión incontrolada o arritmia clínicamente significativa
. QTcF >470 ms en el electrocardiograma (ECG) de selección o síndrome de QT prolongado congénito
 .Infarto de miocardio agudo o angina de pecho inestable < 3 meses antes de entrar en el estudio
3. Enfermedad autoinmune activa o antecedentes documentados de enfermedad autoinmune incluyendo colitis ulcerosa y enfermedad de Crohn o cualquier condición que precise esteroides sistémicos, excepto vitíligo o atopia/asma resuelta que sea tratada con broncodilatadores (por ejemplo, albuterol). Los pacientes expuestos previamente a tratamiento con anti-PD/PD-L1que sean tratados adecuadamente para erupción cutánea o con terapia de sustitución para endocrinopatías, no deberían ser excluidos.
4. Terapia sistémica con esteroides o cualquier terapia inmunosupresora (≥10mg/día de prednisona o equivalente). Los esteroides tópicos, inhalados, nasales u oftalmológicos no están prohibidos.
5. Uso de cualquier vacuna contra enfermedades infecciosas (por ejemplo, varicela, pneumococo) dentro de las 4 semanas del inicio del tratamiento del estudio.
6. Pacientes que hayan recibido las siguientes terapias:
- Terapia antineoplásica sistémica dentro de las 2 semanas de la primera dosis del tratamiento del estudio. Para agentes citotóxicos con toxicidad retardada importante, por ejemplo, mitomicina C y nitrosureas, se indica un periodo de lavado de 4 semanas.
- Pretratamiento con anticuerpos anti-CTLA en combinación con cualquier otro anticuerpo o fármaco dirigido específicamente a coestimulación de las células-T o a la vía de señalización de puntos de control. Los pacientes pretratados con anti-CTLA-4 en monoterapia deberán tener un periodo mínimo de lavado de 8 semanas entre la última dosis del anti-CTLA-4 y la primera dosis de PDR001.
- Participación en un estudio intervencionista, en investigación no inmunoterapéutico, dentro de las 2 semanas de la primera dosis del tratamiento del estudio.
- Cirugía mayor dentro de las 2 semanas de la primera dosis del tratamiento del estudio (la mediastinoscopia, la inserción de catéter venoso central y la inserción de una sonda de alimentación no se consideran cirugía mayor)
-Uso de factores de crecimiento hematopoyéticos estimulantes de colonias (por ejemplo, G-CSF, GM-CSF-M-CSF) y de análogos de trombopoyetina ≤2 semanas antes del inicio de la medicación del estudio. Se permite un agente estimulante de eritrocitos siempre y cuando haya sido iniciado por lo menos 2 semanas antes de la primera dosis del tratamiento del estudio y el paciente mantenga una dosis estable.
-Radioterapia dentro de las 2 semanas de la primera dosis de la medicación del estudio, excepto para radioterapia paliativa de campo limitado, como para el tratamiento de dolor óseo o de una masa tumoral focalmente dolorosa. Para permitir la evaluación de la respuesta al tratamiento, los pacientes incluidos en la parte de la fase II deberán presentar enfermedad medible restante que no haya sido irradiada
7. Pacientes que reciban tratamiento con fármacos que sean inductores o inhibidores potentes de CYP2C8 o de CYP3A4/5 o pacientes que reciban medicación que prohíba inhibidores de la bomba de protones y que no puedan ser suspendidas por lo menos 1 semana antes de iniciar el tratamiento del estudio y durante todo el estudio.
8. Infección conocida por virus de la inmunodeficiencia humana (VIH), virus de la hepatitis B (VHB) activa o virus de la hepatitis C (VHC) activa. Los pacientes cuya infección por VHB o VHC esté controlada con terapia antiviral no deberían ser excluidos.

E.5 End points

E.5.1

Primary end point(s)

Phase I: Safety_ Incidence and severity of Adverse Events (AEs) and serious Adverse Events (SAEs), including changes in laboratory parameters, vital signs and electrocardiogram (ECGs)
Tolerability: Dose interruptions, reductions and dose intensity
The incidence of DLTs during the first cycle of treatment with single agent BLZ945 and with BLZ945 in combination with PDR001
Phase II: Progression free survival (PFS) per response evaluation criteria in solid tumors (RECIST v1.1) for solid tumors (such as pancreatic cancer and triple negative breast cancer indications). PFS per response assessment in Neuro-Oncology (RANO) Criteria for glioblastoma indication.

Fase I:Incidencia y severidad de acontecimientos adversos (AAs) y de acontecimientos adversos graves (AAGs), incluyendo cambios en los valores de laboratorio, constantes vitales y electrocardiogramas (ECGs).
Tolerabilidad: Interrupciones de dosis, reducciones e intensidad de dosis. La incidencia de Dosis Limitante de Dosis (DLTs) durante el primer ciclo de tratamiento con el fármaco BLZ945 en monoterapia y con BLZ945 en combinación con PDR001.
Fase II: Supervivencia libre de progresión (SLP) según criterios de evaluación de respuesta en tumores sólidos (RECIST v.1.1) como el cáncer de páncreas y cáncer de mama triple negativo. Supervivencia libre de progresión (SLP) según criterios de evaluación de respuesta en Neuro-Oncologia (RANO)para la indicación de Glioblastoma.

E.5.1.1

Timepoint(s) of evaluation of this end point

End of study

Final del estudio

E.5.2

Secondary end point(s)

Phase I:
Pharmacodynamics Tumor changes from baseline of immunological markers such as, but not restricted to CD163, CD8, Foxp3 (by immunohistochemistry)
PFS, Best Overall Response (BOR), Duration of Response (DOR) per RECIST v1.1 and immune-related response criteria (irRC)
Phase II: PFS per irRC for solid tumors (such as pancreatic cancer and triple negative breast cancer indications)
PFS per immune response assessment in Neuro-Oncology (iRANO) for glioblastoma indication
BOR, DOR per RECIST v1.1 and irRC for pancreatic cancer and triple negative breast cancer indications
BOR, DOR per RANO and iRANO for glioblastoma indication
Overall survival (OS)
BLZ945 and PDR001 PK parameters [e.g. AUC, Cmax, Tmax]
Presence and/or concentration of anti-PDR001 antibodies

Fase I: Cambios en la farmacodinamia del tumor desde el estado basal de marcadores inmunológicos tales como (pero no restringidos a) CD163, CD8, Foxp3 (por inmunohistoquimica). Supervivencia libre de progresión (SLP), Mejor respuesta global (MRG), duración de la respuesta (DR) según criterios RECIST v. 1.1 y criterios inmunorecist (irRC)
Fase II: Supervivencia libre de progresión (SLP) por irRC para tumores sólidos (tales como indicaciones en cáncer de páncreas y cáncer de mama triple negativo). Supervivencia libre de progresión (SLP) por evaluación de respuesta inmune en neuro-oncologia (iRANO) para la indicación de Glioblastoma.
Mejor respuesta global, Duración de la respuesta por RECIST v 1.1 e irRC en indicaciones de cáncer de páncreas y cáncer de mama triple negativo.
Mejor respuesta global, Duración de la respuesta según RANO y iRANO para la indicación de glioblastoma
Supervivencia Global (SG)
Parámetros farmacocinéticos de BLZ945 y PDR001 (ej, AUC, Cmax, Tmax).
Presencia y/o concentración de anticuerpos anti-PDR001)

E.5.2.1

Timepoint(s) of evaluation of this end point

End of study

Final del estudio

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

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

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

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

Australia

Israel

Italy

Japan

Singapore

Spain

Switzerland

Taiwan

United States

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 will be when at least 80% of the patients have completed the survival follow-up period (minimum 18 months after the first dose of treatment), or discontinued the study for any reason, and all patients have completed treatment as well as the 30-day (BLZ945 single agent) or 90-day (BLZ945 in combination with PDR001) safety follow-up period.

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

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:

101

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

151

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

Ninguno

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

2016-10-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-09-28

P. End of Trial
P.	End of Trial Status	Prematurely Ended

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials