Clinical Trials Register

Summary
EudraCT Number:	2016-003912-11
Sponsor's Protocol Code Number:	Sym015-01
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:	2016-12-27
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

2016-003912-11

A.3

Full title of the trial

An Open-label, Multicenter Phase 1a/2a Trial Investigating the Safety, Tolerability and Antitumor Activity of Multiple Doses of Sym015, a Monoclonal Antibody Mixture Targeting MET, in Patients with Advanced Solid Tumor Malignancies

Ensayo de fase 1a/2a, abierto y multicéntrico, para investigar la seguridad, tolerabilidad y actividad antitumoral de dosis repetidas de Sym015, una mezcla de anticuerpos monoclonales dirigida frente al receptor MET, en pacientes con tumores malignos sólidos en fase avanzada

A.3.1

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

Sym015 (Anti-MET) in Patients with Advanced Solid Tumor Malignancies

Sym015 (Anti MET) en pacientes con tumores malignos sólidos en fase avanzada

A.3.2

Name or abbreviated title of the trial where available

Sym015 (Anti-MET) in Patients with Advanced Solid Tumor Malignancies

A.4.1

Sponsor's protocol code number

Sym015-01

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02648724

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	Symphogen A/S
B.1.3.4	Country	Denmark
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	Symphogen A/S
B.4.2	Country	Denmark
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Symphogen A/S
B.5.2	Functional name of contact point	Ivan Horak
B.5.3	Address:
B.5.3.1	Street Address	Pederstrupvej 93
B.5.3.2	Town/ city	Ballerup
B.5.3.3	Post code	2750
B.5.3.4	Country	Denmark
B.5.4	Telephone number	+4520552604
B.5.5	Fax number	+4545265060
B.5.6	E-mail	idh@symphogen.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	Sym015
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	-
D.3.9.1	CAS number	1879015-24-3
D.3.9.2	Current sponsor code	Sym015
D.3.9.3	Other descriptive name	Humanized IgG1 anti-MET
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.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 Tumor Malignancies

Tumores malignos sólidos en fase avanzada

E.1.1.1

Medical condition in easily understood language

Cancer

Cáncer

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	10065143
E.1.2	Term	Malignant solid tumour
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the antitumor activity of Sym015 when administered at the Q2W RP2D to patients with MET-amplified, KRAS WT solid tumor malignancies without available therapeutic options.

Evaluar la actividad antitumoral del Sym015 administrada cada dos semanas (Q2W RP2D) a pacientes con tumores sólidos malignos con KRAS WT y amplificación de MET, sin opciones terapéuticas disponibles.

E.2.2

Secondary objectives of the trial

1. To further evaluate the safety and tolerability of Sym015 when administered at the Q2W RP2D
2. To further evaluate the PK profile of Sym015 when administered at the Q2W RP2D
3. To further evaluate the immunogenicity of Sym015 when administered at the Q2W RP2D
4. To further evaluate potential pharmacodynamic biomarkers of Sym015 action, and estimate, if feasible, the magnitude of biological activity when administered at the Q2W RP2D
5. To make a preliminary evaluation of the antitumor activity of Sym015, and to evaluate all of the above secondary objectives, in a cohort of patients administered Sym015 on a Q3W dosing schedule at the highest safe dose tested in Part 1

1. Evaluar la seguridad y la tolerabilidad del Sym015 administrada cada dos semanas Q2W RP2D
2. Evaluar el perfil de farmacocinética (PK) del Sym015 administrada cada dos semanas Q2W RP2D
3. Evaluar la inmunogenicidad del Sym015 administrada cada dos semanas Q2W RP2D
4. Evaluar posibles biomarcadores farmacodinámicos de la acción Sym015 y estimar, si es posible, la magnitud de la actividad biológica cuando se administra cada dos semanas Q2W RP2D
5. Realizar una evaluación preliminar de la actividad antitumoral del Sym015, y evaluar todos los objetivos secundarios arriba mencionados, in una cohorte de pacientes que recibieron Sym015 cada tres semanas Q3W a la máxima dosis segura examinada en la Parte 1

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Main inclusion criteria all patients, Part 1 and Part 2:
• Male or female, at least 18 years of age at the time of informed consent
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
• Life expectancy > 3 months assessed during Screening
• Documented (histologically- or cytologically-proven) solid tumor malignancy that is locally advanced or metastatic, and that is refractory to standard therapy or for which no standard therapy is available
• Tumor documented to be KRAS WT by local assessment (i.e. the tumor must express the KRAS WT, exon 2, 3 and 4)

Additional main inclusion criteria applicable to Part 2, Basket Cohort patients ONLY:
• Measurable disease according to RECIST v1.1 that has been confirmed by computed tomography (CT) or magnetic resonance imaging (MRI) within 4 weeks prior to Cycle 1/Day 1 (C1/D1)
• Confirmed MET-amplification

Principales criterios de inclusión para todos los pacientes, Parte 1 y Parte 2:
- Hombre o mujer con una edad mínima de 18 años en el momento del consentimiento informado
- Estado funcional (PS, performance status) del ECOG (Eastern Cooperative Oncology Group) de 0 ó 1
- Esperanza de vida > 3 meses, evaluada en la selección
- Tumor sólido maligno documentado (demostrado histológica o citológicamente), localmente avanzado o metastásico y resistente al tratamiento estándar o para el que no existe un tratamiento estándar disponible o accesible
- Tumor con KRAS WT determinado según el análisis del laboratorio local con arreglo a las normas del centro, (ejemplo, el tumor debe expresar KRAS WT, exón 2, 3 y 4)

E.4

Principal exclusion criteria

Main exclusion criteria all patients, Part 1 and Part 2:
• Any antineoplastic agent (standard or investigational) within 4 weeks prior to C1/D1
• Immunosuppressive or systemic hormonal therapy within 2 weeks prior to C1/D1 with specified allowed exceptions
• Use of hematopoietic growth factors within 2 weeks prior to C1/D1
• Active second malignancy or history of another malignancy within the last 3 years, with specified allowed exceptions
• Central nervous system (CNS) malignancy including primary malignancies of the CNS, known CNS or leptomeningeal metastases not controlled by prior surgery or radiotherapy, or symptoms suggesting CNS involvement for which treatment is required
• Inadequate recovery from an acute toxicity associated with any prior antineoplastic therapy
• Major surgical procedure within 4 weeks prior to C1/D1 or inadequate recovery from any prior surgical procedure
• Active thrombosis, or a history of deep vein thrombosis or pulmonary embolism, within 1 month prior to C1/D1, unless adequately treated and stable
• Active uncontrolled bleeding or a known bleeding diathesis
• Significant cardiovascular disease or condition
• Abnormal hematologic, renal or hepatic function
• Any of the following within 2 weeks prior to C1/D1:
o Any serious or uncontrolled infection
o Any infection requiring parenteral antibiotics
o Unexplained fever > 38.0 °C

Principales criterios de inclusión para todos los pacientes, Parte 1 y Parte 2:
- Tratamiento antineoplásico (estándar o en investigación) en el plazo de las 4 semanas anteriores al C1/D1
- Tratamiento inmunosupresor u hormonal sistémico en el plazo de las 2 semanas anteriores al C1/D1, salvo las excepciones permitidas que se indican
- Tratamiento con factores de crecimiento hematopoyéticos en el plazo de las 2 semanas anteriores al C1/D1
- Segunda neoplasia maligna activa o antecedentes de otro proceso maligno en los últimos 3 años, salvo las excepciones permitidas que se indican
- Neoplasia maligna del sistema nervioso central (CNS, central nervous system), ya sea primaria y/o metastásica o metástasis leptomeníngeas, que no se haya controlado mediante cirugía o radioterapia previas, o síntomas indicativos de afectación del sistema nervioso central que requieran tratamiento
- Recuperación insuficiente de un efecto tóxico agudo resultante de un tratamiento antineoplásico anterior
- Intervención quirúrgica mayor en el plazo de las 4 semanas anteriores al C1/D1 o recuperación insuficiente de una intervención quirúrgica previa
- Trombosis activa o antecedentes de trombosis venosa profunda o embolia pulmonar en el mes anterior al C1/D1, salvo que reciba el tratamiento adecuado y se mantenga estable
- Hemorragia activa no controlada o diagnóstico de diátesis hemorrágica
- Enfermedad o proceso cardiovascular importante
- Alteración funcional hematológica, renal o hepática
- Presentación en el plazo de las 2 semanas anteriores al C1/D1 de cualquiera de las siguientes situaciones:
. Infección grave o no controlada
. Infección que requirió antibioterapia parenteral
. Fiebre de filiación desconocida > 38.0 °C

E.5 End points

E.5.1

Primary end point(s)

Documented objective response (OR) (defined as partial response [PR] or complete response [CR]) in the Q2W Basket Cohort, assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Respuesta objetiva (OR, objective response) documentada (definida como una respuesta parcial [PR, partial response] o una respuesta completa [CR, complete response]) en la Cohorte Cesto Q2W, evaluada por los Criterios de Evaluación de la Respuesta en Tumores Sólidos (RECIST, Response Evaluation Criteria in Solid Tumors) v1.1

E.5.1.1

Timepoint(s) of evaluation of this end point

At any time during trial participation by Investigator assessment

En cualquier momento durante la participación en el ensayo evaluada por el investigador

E.5.2

Secondary end point(s)

NAP

E.5.2.1

Timepoint(s) of evaluation of this end point

NAP

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

Yes

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

Safety, tolerability and Antitumor Activity of Multiple Doses study

Estudio de la seguridad, tolerabilidad y actividad antitumoral de dosis repetidas

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

Denmark

Hong Kong

Korea, Republic of

Spain

Taiwan

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

Última visita del 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

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

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

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

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

2017-03-01

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-02-17

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2020-12-17

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