Clinical Trials Register

Summary
EudraCT Number:	2020-000848-57
Sponsor's Protocol Code Number:	GCT3013-03
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2022-10-06
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2020-000848-57

A.3

Full title of the trial

A Phase 1b/2, Open-Label, Safety and Efficacy Study of Epcoritamab (GEN3013; DuoBody®-CD3 X CD20) in Relapsed/Refractory Chronic Lymphocytic Leukemia and Richter’s Syndrome

Estudio abierto de fase Ib/II para evaluar la seguridad y la eficacia de epcoritamab (GEN3013; DuoBody®-CD3 × CD20) en pacientes con leucemia linfocítica crónica recidivante/refractaria y síndrome de Richter

A.3.1

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

Safety and Efficacy Study of Epcoritamab in Subjects with Relapsed/Refractory Chronic Lymphocytic Leukemia and Richter’s Syndrome

Estudio de la seguridad y la eficacia de epcoritamab en sujetos con leucemia linfocítica crónica recidivante/refractaria y síndrome de Richter

A.4.1

Sponsor's protocol code number

GCT3013-03

A.5.4

Other Identifiers

Name:

IND Number

Number:

135659

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	Genmab 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	Genmab A/S
B.4.2	Country	Denmark
B.4.1	Name of organisation providing support	Genmab US, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Genmab A/S
B.5.2	Functional name of contact point	Clinical Trial Information
B.5.3	Address:
B.5.3.1	Street Address	Kalvebod Brygge 43
B.5.3.2	Town/ city	Copenhagen V
B.5.3.3	Post code	1560
B.5.3.4	Country	Denmark
B.5.6	E-mail	regulatory@genmab.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	Epcoritamab
D.3.2	Product code	GEN3013
D.3.4	Pharmaceutical form	Concentrate and solvent for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	epcoritamab
D.3.9.1	CAS number	2134641-34-0
D.3.9.2	Current sponsor code	GEN3013
D.3.9.3	Other descriptive name	GEN3013
D.3.9.4	EV Substance Code	SUB190479
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	5
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	epcoritamab
D.3.9.1	CAS number	2134641-34-0
D.3.9.3	Other descriptive name	GEN3013
D.3.9.4	EV Substance Code	SUB190479
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	60
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

Chronic Lymphocytic Leukemia

Leucemia Linfocítica Crónica

E.1.1.1

Medical condition in easily understood language

Chronic Lymphocytic Leukemia

Leucemia Linfocítica Crónica

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
E.1.2	Level	LLT
E.1.2	Classification code	10008976
E.1.2	Term	Chronic lymphocytic leukemia
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

• Identify the RP2D and the MTD of epcoritamab
• Evaluate the safety and tolerability of epcoritamab

• Identificar la DRF2 y la DMT de epcoritamab
• Evaluar la seguridad y la tolerabilidad de epcoritamab

E.2.2

Secondary objectives of the trial

• Characterize the pharmacokinetic properties of epcoritamab
• To evaluate pharmacodynamic markers linked to efficacy and mechanism of action of epcoritamab
• Evaluate immunogenicity of epcoritamab
• Assess the preliminary anti-tumor activity of epcoritamab

• Caracterizar las propiedades farmacocinéticas de epcoritamab
• Evaluar los marcadores farmacodinámicos asociados a la eficacia y mecanismo de acción de epcoritamab
• Evaluar la inmunogenicidad de epcoritamab
• Evaluar la actividad antitumoral preliminar de epcoritamab

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

All Subjects
• Subject must sign an ICF, prior to any screening procedures
• Must be at least 18 years of age
• ECOG performance status score of 0,1 or 2
• Evidence of CD20 positivity at screening
• Has acceptable laboratory parameters
• Subject must have availability of fresh bone marrow material at screening
• A woman with reproductive potential must agree to use adequate contraception during the trial, and for 12 months after the last administration of epcoritamab.
• A woman of childbearing potential must have a negative serum (beta-hCG) pregnancy test at screening and a negative serum or urine pregnancy test before treatment administration on Day 1 of every cycle.
• A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the entire trial, until 12 months after last treatment.
• A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control.

Inclusion Criteria Specific to the R/R CLL Cohort
• Must have active CLL disease that needs treatment
•R/R CLL after receiving at least 2 prior lines of systemic antineoplastic therapy
• Has measurable disease with at least one of the following criteria:
a. ≥5 × 109/L (5,000/μL) B lymphocytes in peripheral blood
b. Presence of measurable lymphadenopathy and/or organomegaly
• Must take prophylaxis for TLS

Inclusion Criteria Specific to the Richter’s Syndrome Cohort
• Must have a clinical history of CLL/SLL with biopsy-proven transformation toward aggressive lymphoma (ie, DLBCL subtype).
• Deemed as ineligible for chemoimmunotherapy at investigator’s discretion or refuse to receive intensive chemotherapy.
• Must have measurable disease

Todos los sujetos:
• El sujeto debe firmar un DCI antes de que se lleve a cabo cualquier procedimiento de selección
• Tener al menos 18 años de edad
• Puntuación del estado general ECOG de 0, 1 o 2.
• Evidencia de positividad para CD20 en la selección.
• Tiene parámetros analíticos aceptables
• El sujeto debe tener disponible una muestra de médula ósea reciente en la selección
• Una mujer en edad fértil debe aceptar el uso de métodos anticonceptivos adecuados durante el ensayo y durante los 12 meses después de la última administración de epcoritamab.
• Una mujer en edad fértil debe presentar una prueba del embarazo en suero (β-hCG) negativa en la selección y una prueba del embarazo en suero o en orina negativa antes de la administración del tratamiento el día 1 del ciclo 1.
• La mujer debe comprometerse a no donar óvulos con fines de reproducción asistida durante todo el ensayo, hasta 12 meses después del último tratamiento.
• Un hombre sexualmente activo con una mujer en edad fértil que no se haya sometido a una vasectomía debe aceptar el uso de un método anticonceptivo de barrera.

Criterios de inclusión específicos para cohorte con LLC R/R:
• Deben tener LLC activa que necesite tratamiento.
• LLC R/R después de recibir al menos 2 líneas previas de tratamiento antineoplásico sistémico.
• Tener enfermedad medible con al menos uno de los siguientes criterios:
a. ≥5 × 109/l (5000/μl) linfocitos B en sangre periférica
b. Presencia de linfadenopatía medible y/u organomegalia
• Debe tomar profilaxis para el SLT

Criterios de inclusión específicos para cohorte con Síndrome de Ritcher:
• Deben tener antecedentes clínicos de LLC/LLP con transformación de LMDLB en biopsia.
• Considerados como no aptos para la quimioinmunoterapia a discreción del investigador o negarse a recibir quimioterapia intensiva.
• Deben presentar enfermedad medible

E.4

Principal exclusion criteria

All Subjects
• Subject received prior treatment with a CD3 × CD20 bispecific antibody.
• Subject received any prior allogeneic HSCT or solid organ transplantation
• Subject received treatment with an anti-cancer agent, eg:
a. Small molecules such as BTK inhibitor, BCL2 inhibitor, or PI3K inhibitor within 5 half-lives prior to the first dose of epcoritamab; or
b. Anti-CD20 mAb or chemotherapy within 2 weeks prior to the first dose of epcoritamab;
or
c. Radio-conjugated or toxin conjugated antibody or CAR-T cell therapy within 4 weeks or 5 half-lives, whichever is shorter, prior to the first dose of epcoritamab
d. Subject received treatment with an investigational drug, within 4 weeks or 5 half-lives, whichever is shorter prior to the first dose of epcoritamab.
• Subject has autoimmune disease or other diseases that require permanent or high-dose immunosuppressive therapy.
• Subject has clinically significant cardiac disease
• Subject received vaccination with live vaccines within 28 days prior to the first dose of epcoritamab
• Subject has known central nervous system (CNS) involvement at screening.
• Has had major surgery within 4 weeks prior to enrollment.
• Known medical history or ongoing hepatitis C infection that has not been cured.
• Known history of seropositivity for HIV infection. Note: HIV testing is required at screening only if required per local health authorities or institutional standards.
• Subject is a woman who is pregnant or breast-feeding, or who is planning to become pregnant while enrolled in this trial or within 12 months after the last dose of epcoritamab.
• Subject is a man who plans to father a child while enrolled in this trial or within 12 months after the last dose of epcoritamab.
• Subject has uncontrolled intercurrent illness, such as ongoing or active infection requiring intravenous antibiotics treatment at the time of enrollment or within the previous 2 weeks prior to the first dose of epcoritamab.

Exclusion Criteria Specific to the R/R CLL Cohort:
• Any history of RS or evidence indicating a potential Richter’s transformation.
• Subject is unable to tolerate uric acid reducing medications.

Exclusion Criteria Specific to the Richter’s Syndrome Cohort
• Diagnosis of Richter's syndrome not of the DLBCL subtype such as Hodgkin’s lymphoma, prolymphocytic leukemia.
• Subject received autologous HSCT within 3 months prior to the first dose of epcoritamab.
• Subject received more than 1 prior line of therapy for RS.

Todos los sujetos:
• El sujeto recibió tratamiento previo con un anticuerpo biespecífico CD3 × CD20.
• El sujeto recibió un trasplante alogénico de TCMH o de órganos sólidos.
• El paciente recibió tratamiento con un medicamento antineoplásico, p. ej.:
a. moléculas pequeñas como el inhibidor de BTK, el inhibidor de BCL2 o el inhibidor de PI3K en el plazo de 5 semividas antes de la primera dosis de epcoritamab; o
b. anticuerpo monoclonal anti-CD20 o quimioterapia en las 2 semanas previas a la primera dosis de epcoritamab; o
c. tratamiento con anticuerpos conjugados con radio o toxinas o linfocitos T-CAR en las 4 semanas o 5 semividas, lo que sea más corto, antes de la primera dosis de epcoritamab.
d. El sujeto ha recibido tratamiento con un fármaco en investigación en las 4 semanas o 5 semividas previas a la primera dosis de epcoritamab, lo que sea más corto.
• El sujeto tiene una enfermedad autoinmunitaria u otras enfermedades que requieran tratamiento inmunodepresor permanente o en dosis altas.
• El sujeto tiene una enfermedad cardíaca clínicamente significativa
• Se vacunó al sujeto con vacunas elaboradas con microbios vivos en los 28 días anteriores a la primera dosis de epcoritamab.
• El sujeto tiene una afectación conocida del sistema nervioso central (SNC) en la selección.
• Haberse sometido a una cirugía mayor en las 4 semanas anteriores a la selección.
• Antecedentes médicos conocidos o infección por el virus de la hepatitis C en curso que no se ha curado.
• Antecedentes conocidos de seropositividad para la infección por el VIH. Nota: la prueba del VIH se requiere en la evaluación solo si así lo exigen las autoridades sanitarias locales o las normas institucionales.
• El sujeto es una mujer que está embarazada o en periodo de lactancia o que tiene previsto quedarse embarazada mientras esté inscrita en este ensayo o en un plazo de 12 meses después de la última dosis de epcoritamab.
• El sujeto es un hombre que tiene previsto tener hijos mientras esté inscrito en este ensayo o en un plazo de 12 meses después de la última dosis de epcoritamab.
• El sujeto tiene una enfermedad intercurrente no controlada, como infección activa o en curso que requiere tratamiento con antibióticos por vía intravenosa en el momento de la inscripción o en las 2 semanas previas a la primera dosis de epcoritamab.

Criterios de exclusión específicos para cohorte con LLC R/R:
• Cualquier antecedente de SR o evidencia que indique una posible transformación de Richter.
• El sujeto es incapaz de tolerar los medicamentos para reducir el ácido úrico.

Criterios de exclusión específicos para cohorte con Síndrome de Ritcher:
• Diagnóstico de síndrome de Richter que no es del subtipo de LMDLB como linfoma de Hodgkin o leucemia prolinfocítica.
• El sujeto recibió TCMH autólogo en los 3 meses anteriores a la primera dosis de epcoritamab.
• El sujeto recibió más de 1 línea de tratamiento anterior para el SR.

E.5 End points

E.5.1

Primary end point(s)

• Incidence of DLTs
• Incidence and severity of AEs and SAEs.
• Incidence and severity of CRS, ICANS and TLS
• Incidence of dose interruption, dose delay, and dose intensity

• Incidencia de las TLD
• Incidencia e intensidad de los acontecimientos adversos (AA) y de los acontecimientos adversos graves (AAG).
• Incidencia e intensidad de SLC, ICANS y síndrome de lisis tumoral (SLT)
• Incidencia de la interrupción de la dosis, retraso de la dosis e intensidad de la dosis

E.5.1.1

Timepoint(s) of evaluation of this end point

DLT evaluation period is defined as the first 4 weeks, ie, 28 days after the first administration ofepcoritamab.
For the other end points, please refer to protocol

El período de evaluación de TLD se define como las primeras 4 semanas, es decir, 28 días después de la primera administración de epcoritamab.
Para los otros puntos finales, consulte el protocolo

E.5.2

Secondary end point(s)

• PK parameters (eg, clearance, volume of distribution and AUC0-last and AUC0-∞, Cmax, Tmax, predose values, and t½)
• Pharmacodynamic markers in blood samples
• Incidence of ADAs to epcoritamab
• ORR
• CR/CRi rate
• DOR
• TTR
• PFS
• OS

• Parámetros farmacocinéticos(p. ej., aclaramiento, volumen de distribución y ABC0-últ. y ABC0-∞, Cmáx., Tmáx., valores antes de la dosis y t1⁄2)
• Parámetros farmacodinámicos en las muestras de sangre
• Incidencia de los anticuerpos antifármaco (AAF) contra epcoritamab
• Tasa de respuesta global (TRG)
• Tasa de remisión completa (RC) o RC con recuperación incompleta de la médula (RCi)
• Duración de la respuesta (DR)
• Tiempo hasta la respuesta (THR)
• Supervivencia sin progresión (SSP)
• Supervivencia global (SG)

E.5.2.1

Timepoint(s) of evaluation of this end point

Please refer to protocol

Por favor consultar protocolo

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 1b/2

Fase 1b/2

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

United States

France

Netherlands

Spain

Germany

Italy

Belgium

Denmark

United Kingdom

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

Last Visit Last Site (LVLS)

Última visita último centro

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

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)

When a patient is no longer in the trial, further treatment is at the discretion of the patient's doctor

Cuando un paciente ya no está en el ensayo, el tratamiento adicional queda a discreción del médico del paciente.

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

2023-03-01

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2023-02-20

P. End of Trial
P.	End of Trial Status	Ongoing

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