Clinical Trials Register

Summary
EudraCT Number:	2016-000210-29
Sponsor's Protocol Code Number:	CMCS110Z2102
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2016-04-01
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

2016-000210-29

A.3

Full title of the trial

A Phase Ib/II, open label, multicenter study of MCS110 in combination with PDR001 in patients with advanced malignancies

Estudio fase Ib/II, abierto, multicéntrico de MCS110 en combinación con PDR001, en pacientes con neoplasias malignas avanzadas

A.3.1

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

A clinical study of the compound MCS110 in combination with the compound PDR001 in patients with advanced cancers

Estudio clínico con el compuesto MCS110 en combinación con PDR001 en
pacientes con cáncer avanzado

A.4.1

Sponsor's protocol code number

CMCS110Z2102

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 Farmacéutica, 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 Services 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 Farmacéutica, S.A.
B.5.2	Functional name of contact point	Departamento Médico Oncología
B.5.3	Address:
B.5.3.1	Street Address	Gran Vía 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	+34900353036
B.5.5	Fax number	+34932479903
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.3.1	Product name	MCS110
D.3.2	Product code	MCS110
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	not yet defined
D.3.9.1	CAS number	-
D.3.9.2	Current sponsor code	MCS110
D.3.9.3	Other descriptive name	MCS110
D.3.9.4	EV Substance Code	SUB32640
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	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	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	PDR001
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 yet defined
D.3.9.1	CAS number	-
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 malignancies

neoplasias malignas avanzadas

E.1.1.1

Medical condition in easily understood language

Advanced cancers

Cánceres 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	18.1
E.1.2	Level	LLT
E.1.2	Classification code	10048683
E.1.2	Term	Advanced cancer
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 Ib part:
To characterize the safety and tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II.

Phase II part:
To estimate the anti-tumor activity of the combination of MCS110 with PDR001

Parte fase Ib:
Caracterizar la seguridad y la tolerabilidad de MCS110 en combinación con PDR001 en pacientes con tumores sólidos avanzados e identificar una combinación de dosis recomendada para la fase II.

Parte fase II: Calcular la actividad antineoplásica de la combinación de MCS110 con PDR001

E.2.2

Secondary objectives of the trial

Phase Ib part:
1. To estimate the preliminary anti-tumor activity of the combination of MCS110 with PDR001

Phase II part:
2. To further characterize the safety and tolerability of MCS110 given in combination with PDR001
3. To evaluate the preliminary anti-tumor activity of the combination of MCS110 with PDR001 by additional efficacy measures

Phase Ib and Phase II parts:
4. To characterize the pharmacokinetics of MCS110 and PDR001 in combination
5. To assess immunogenicity of MCS110 and PDR001
6. To describe survival with MCS110 and PDR001 in combination

Parte fase Ib:
1. Evaluar mejor la actividad antineoplásica preliminar de la combinación de MCS110 con PDR001.

Parte fase II:
2. Caracterizar mejor la seguridad y la tolerabilidad de MCS110 administrado en combinación con PDR001.
3. Evaluar mejor la actividad antineoplásica preliminar de la combinación de MCS110 con PDR001 con medidas de eficacia adicionales.

Partes fase Ib y II:
4. Caracterizar la farmacocinética de la combinación de MCS110 con PDR001.
5. Valorar la inmunogenicidad de MCS110 and PDR001.
6. Describir la supervivencia con MCS110 y PDR001 administrados en combinación.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Age >/= 18 years.
- Phase Ib part: Patients with advanced melanoma, endometrial carcinoma, pancreatic or triple negative breast cancer, with measurable or non-measurable disease as determined by RECIST version 1.1, who have progressed despite standard therapy or are intolerant of standard therapy, or for whom no standard therapy exists.
- Phase II part: Patients with advanced solid tumors with at least one measurable lesion as determined by RECIST version 1.1, who have received standard therapy or are intolerant of standard therapy, who have progressed following their last prior therapy, and fit into one of the following groups:
- Group 1: TNBC who did not receive prior anti-PD-1/PD-L1 treatment
- Group 2 : Pancreatic adenocarcinoma who did not receive prior anti-PD-1/PD-L1 treatment
- Group 3 : Endometrial carcinoma who did not receive prior anti-PD-1/PD-L1 treatment
- Group 4: Melanoma who progressed on prior PD-1- and PD-L1-directed therapies.
- ECOG Performance Status </= 2.
- Patient 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 therapy on this study. Exceptions for patients with sites of disease not amenable to biopsy may be considered after discussion with the sponsor.

Other inclusion criteria as per protocol may apply.

-Edad >/= 18 años
-Parte fase Ib: Pacientes con cáncer de mama triple negativo, pancreático, carcinoma endometrial o melanoma avanzado, con neoplasia medible o no medible, determinado con la versión 1.1 de los RECIST, que hayan progresado a pesar de terapia estándar, que no toleren la terapia estándar o para los que no exista la terapia estándar.
-Parte fase II: Pacientes con tumores sólidos avanzados con por lo menos una lesión medible, determinado con la versión 1.1 de los RECIST, que hayan recibido terapia estándar, que no toleren la terapia
estándar, que hayan progresado tras su última terapia previa y que encajen en uno de los grupos siguientes:
-Grupo 1: CMTN que no haya recibido tratamiento previo anti-PD-1/PD-L1
-Grupo 2: Adenocarcinoma pancreático que no haya recibido tratamiento previo anti-PD-1/PD-L1
-Grupo 3: Carcinoma endometrial que no haya recibido tratamiento previo anti-PD-1/PD-L1
-Grupo 4: Melanoma que haya progresado con terapias previas dirigidas a PD-1 y PD-L1.
-Estado funcional del ECOG </=2.
Los pacientes deberán presentar una zona de enfermedad apta para biopsia y ser candidatos para biopsia del tumor según las directrices del centro de tratamiento. Los pacientes deberán acceder a ser sometidos a una nueva biopsia
en la selección y durante el estudio. Las excepciones para los pacientes sin lesiones aptas para biopsiar pueden considerarse tras discusión con el promotor.

Pueden aplicar otros criterios de inclusión de acuerdo al protocolo.

E.4

Principal exclusion criteria

-Presence of symptomatic CNS metastases, or CNS metastases thatrequire local CNS-directed therapy
-History of severe hypersensitivity reactions to other mAbs
-Impaired cardiac function or clinically significant cardiac disease
-Active autoimmune disease or a documented history of autoimmune disease within three years before screening
-Active infection requiring systemic antibiotic therapy
-Known history of HIV infection
-Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, or requiring antiviral treatment

Other exclusion criteria as per protocol may apply.

- Presencia de metástasis sintomáticas del SNC o metástasis del SNC que precisen terapia local dirigida al SNC.
- Antecedentes de reacciones de hipersensibilidad severa a otros anticuerpos monoclonales (mAbs)
- Cardiopatía clínicamente significativa o deterioro de la función cardíaca
- Enfermedad autoimmune activa o antecedentes documentados de enfermedad autoinmune dentro de los tres años antes de la selección.
- Infección activa que precise terapia antibiótica sistémica.
- Antecedentes conocidos de infección por VIH.
- Virus de la hepatitis B (VHB) o infección por virus de la hepatitis C (VHC) activo que precise tratamiento antiviral.
Pueden aplicar otros criterios de exclusión de acuerdo al protocolo.

E.5 End points

E.5.1

Primary end point(s)

Phase 1b part:
Frequency, severity and seriousness of AEs, laboratory abnormalities and other safety parameters.
Dose interruptions, reductions, and dose intensity.
Incidence rate of DLTs

Phase II part:
Overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST v1.1).

Parte fase Ib:
Frecuencia, severidad y gravedad de los AAs, anormalidades de laboratorio y otros parámetros de seguridad. Interrupciones de dosis, reducciones e intensidad de dosis.
Tasa de incidencia de DLTs.

Parte fase II: Tasa de respuesta global (ORR) según Criterios de Evaluación de Respuesta en Tumores Sólidos (RECIST v1.1).

E.5.1.1

Timepoint(s) of evaluation of this end point

Phase 1b part:
hroughout study conduct
Incidence rate of DLTs: during the first two cycles of study treatment.

Phase II part:
at protocol-defined timepoints

Parte fase Ib:
A lo largo del estudio tasa de incidencia de DLTs: durante los dos primeros ciclos de tratamiento del estudio.

Parte fase II:
En los puntos de tiempo definidos en el protocolo.

E.5.2

Secondary end point(s)

Phase Ib part:
1. ORR, progression free survival (PFS), clinical benefit rate (CBR),duration of response (DOR) and disease control rate (DCR) per RECIST v1.1 and per immune related Response Criteria (irRC)

Phase II part:
2. Frequency, severity and seriousness of AEs, laboratory abnormalities and other safety parameters.
3. ORR per irRC, PFS, DOR, DCR, CBR per RECIST v1.1 and per irRC

Phase Ib and Phase II parts:
4. Serum concentration of MCS110 and PDR001 and PK parameters
5. Presence and/or concentration of anti-PDR001 or anti-MCS110 antibodies
6. Overall survival (OS)

Parte fase Ib:
1. ORR (Tasa de respuesta global), Supervivencia libre de progresión (PFS), tasa de beneficio clínico (CBR), duración de respuesta (DOR) y tasa de control de la enfermedad (DCR) por RECIST v 1.1 y por criterios de respuesta inmunorelacionados (irRC).

Parte fase II:
2. Frecuencia, severidad y gravedad de AAs, anormalidades de laboratorio y otros parámetros de seguridad.
3. ORR por irRC, PFS, DOR, DCR, CBR por RECIST v1.1 y por irRC

Partes fase Ib y II:
4. concentración de MCS110 y PDR001 en suero y parámetros farmacocinéticos.
5. Presencia y/o concentración de anticuerpos anti-PDR001 o anti-MCS110
6. Supervivencia global (OS)

E.5.2.1

Timepoint(s) of evaluation of this end point

at protocol-defined timepoints (PK, PD and preliminary anti-tumor activity endpoint).

en los puntos de tiempo definidos en el protocolo (PK, PD y actividad antitumoral)

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

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

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

Phase Ib/II

Fase Ib/II

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

Yes

E.8.4

The trial involves multiple sites in the 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

Belgium

Finland

France

Germany

Hong Kong

Italy

Korea, Republic of

Spain

Switzerland

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

LVLS

Última Visita Último Paciente

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:

105

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

175

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

2016-05-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-05-03

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2020-06-04

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Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
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