Clinical Trials Register

Summary
EudraCT Number:	2020-000845-15
Sponsor's Protocol Code Number:	GCT3013-02
National Competent Authority:	Denmark - DHMA
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2020-06-29
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

Denmark - DHMA

A.2

EudraCT number

2020-000845-15

A.3

Full title of the trial

A Phase 1b/2, Open-Label Trial to Assess the Safety and Preliminary Efficacy of Epcoritamab (GEN3013; DuoBody®-CD3xCD20) in Combination with Other Agents in Subjects with B-cell Non-Hodgkin Lymphoma

A.3.1

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

Safety and Efficacy Trial of Epcoritamab Combinations in Subjects With B-cell Non-Hodgkin Lymphoma

A.4.1

Sponsor's protocol code number

GCT3013-02

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.3.9.3	Other descriptive name	GEN3013 (DuoBody®-CD3xCD20)
D.3.9.4	EV Substance Code	SUB190479
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	5
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	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.3.9.3	Other descriptive name	GEN3013 (DuoBody®-CD3xCD20)
D.3.9.4	EV Substance Code	SUB190479
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	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

B-cell Non-Hodgkin Lymphoma
Diffuse large B-cell lymphoma
Non-Hodgkin lymphoma
Follicular lymphoma

E.1.1.1

Medical condition in easily understood language

Lymphoma of B-cell origin

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	HLGT
E.1.2	Classification code	10025320
E.1.2	Term	Lymphomas non-Hodgkin's B-cell
E.1.2	System Organ Class	10005329 - Blood and lymphatic system disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

Dose Escalation Phase: Evaluate the safety and tolerability of epcoritamab in combination with other agents

Expansion Phase:
Arms 1-6: Assess the preliminary anti-tumor activity of epcoritamab in combination with other agents
Arm 7: Evaluate the safety and tolerability of epcoritamab following standard of care (SOC)

E.2.2

Secondary objectives of the trial

Dose Escalation Phase:
- Characterize the pharmacokinetic (PK) properties of epcoritamab
- Evaluate pharmacodynamic markers linked to efficacy and mechanism of action of epcoritamab
- Evaluate immunogenicity
- Assess the preliminary anti-tumor activity of epcoritamab in combination with other agents

Expansion Phase:
- Further assess the preliminary anti-tumor activity of epcoritamab in combination with other agents
- Further evaluate the safety and tolerability of epcoritamab in combination with other agents
- Characterize the PK properties of epcoritamab
- To evaluate pharmacodynamic markers linked to efficacy and mechanism of action of epcoritamab
- Evaluate immunogenicity

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Subject must sign an ICF
2. At least 18 years of age
3. Measurable disease defined as ≥1 measurable nodal lesion (long axis >1.5 cm and short axis >1.0 cm) or ≥1 measurable extra-nodal lesion (long axis >1.0 cm) on CT or MRI
4. ECOG PS score of 0, 1 or 2
5. Acceptable organ function at screening
6. CD20-positive NHL at most recent representative tumor biopsy
7. If of childbearing potential subject must practicing a highly effective method of birth control
8. A man who is sexually active with a woman of childbearing potential must agree to use a barrier method of birth control
9. Life expectancy >2 months with SOC treatment.

Arm 1: One of these confirmed histologies:
- DLBCL, NOS
- "double-hit" or "triple-hit" DLBCL
- FL Grade 3B

Arm 2: R/R FL

Arm 3: Newly diagnosed, previously untreated FL grade 1-3A

Arm 4: One of these confirmed histologies and eligible for HDT-ASCT
- DLBCL, NOS
- "double-hit" or "triple-hit" DLBCL
- FL Grade 3B

Arm 5: One of these confirmed histologies and ineligible for HDT-ASCT
- DLBCL, NOS
- "double-hit" or "triple-hit" DLBCL
- FL Grade 3B
Arm 6: previously untreated CD20+ FL
Arm 7: FL and in CR or PR per Lugano criteria following first-line or second-line treatment with SOC regiment

E.4

Principal exclusion criteria

1. Chemotherapy, radiation therapy, or major surgery within 4 weeks prior to the first dose of epcoritamab
2. Any prior treatment with a bispecific antibody targeting CD3 and CD20.
3. Treatment with CAR-T therapy within 30 days prior to first dose of epcoritamab
4. Clinically significant cardiovascular disease
5. Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results
6. CNS lymphoma or known CNS involvement by lymphoma at screening as confirmed by MRI/CT scan of the brain and, if clinically indicated, by lumbar puncture
7. Active HBV or HBC (DNA PCR positive infection)
8. Known history of seropositivity for human immunodeficiency virus (HIV)
9. Suspected active or latent tuberculosis

E.5 End points

E.5.1

Primary end point(s)

Dose Escalation Phase:
- Incidence of dose-limiting toxicities
- Incidence and severity of adverse events (AEs)
- Incidence and severity of changes in laboratory values
- Incidence of dose interruptions and delays

Expansion Phase:
Arms 1-6:
- ORR determined by Lugano criteria
Arm 7:
- Incidence and severity of AEs
- Incidence and severity of changes in laboratory values
- Incidence of dose interruptions and delays

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 of epcoritamab.
For the other end points, please refer to protocol

E.5.2

Secondary end point(s)

Dose Escalation Phase:
- PK parameters (clearance, volume of distribution, area under-the-concentration-time curve [AUC0-Clast and AUC0-∞], maximum concentration [Cmax], time of Cmax [Tmax], predose values, and half-life)
- Pharmacodynamic markers in blood samples and within tumor (on-treatment biopsy)
- Incidence of anti-drug antibodies (ADAs) to epcoritamab
- ORR determined by Lugano criteria
- Duration of response (DOR) determined by Lugano criteria
- Time to response (TTR) determined by Lugano criteria
- Progression-free survival (PFS) determined by Lugano criteria
- ORR determined by Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC)
- DOR determined by LYRIC
- TTR determined by LYRIC
- PFS determined by LYRIC
- Overall survival (OS)
- Time to next anti-lymphoma therapy (TTNT)
- Rate and duration of minimal residual disease (MRD) negativity

Expansion Phase:
-DOR determined by Lugano criteria (Arms 1-6)
-TTR determined by Lugano criteria (Arms 1-6)
-PFS determined by Lugano criteria (Arms 1-6)
-ORR determined by LYRC LYRIC (Arms 1-6)
-DOR determined by LYRIC (Arms 1-6)
-TTR determined by LYRIC (Arms 1-6)
-PFS determined by LYRIC (Arms 1-6)
-OS (Arms 1-7)
-TTNT (Arms 1-7)
-Rate and duration of MRD negativity (Arms 1-7)
-Rate of conversion from MRD positivity to MRD negativity (Arm 7)
-CR rate (Arm 7 subjects in PR at baseline)
-TTCR (Arms 1-7, except Arm 7 subjects in CR at baseline)
-DoCR (Arms 1-7)

E.5.2.1

Timepoint(s) of evaluation of this end point

Please refer to protocol

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

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

Canada

United States

Belgium

Denmark

Finland

France

Italy

Netherlands

Norway

Spain

Sweden

United Kingdom

Czechia

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

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:

188

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

Yes

F.3.3.7.1

Details of other specific vulnerable populations

elderly

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

189

F.4.2.2

In the whole clinical trial

270

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.

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

2020-08-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-08-21

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

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