Clinical Trials Register

Summary
EudraCT Number:	2020-003781-40
Sponsor's Protocol Code Number:	GCT3014-01
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-12-06
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

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2020-003781-40

A.3

Full title of the trial

An Open-Label, Multicenter, Phase 1/2 Trial of GEN3014 (HexaBody®-CD38) in Relapsed or Refractory Multiple Myeloma and Other Hematologic Malignancies

A.3.1

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

Phase 1/2 study of GEN3014 in relapsed or refractory hematologic malignancies

A.3.2

Name or abbreviated title of the trial where available

Phase 1/2 trial of GEN3014 in relapsed or refractory hematologic malignancies

A.4.1

Sponsor's protocol code number

GCT3014-01

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT04824794

A.5.4

Other Identifiers

Name:

IND

Number:

146079

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.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Genmab US Inc
B.5.2	Functional name of contact point	Senior Clinical Trial Manager
B.5.3	Address:
B.5.3.1	Street Address	777 Scudders Mill Road · Bldg. 2
B.5.3.2	Town/ city	Plainsboro
B.5.3.3	Post code	NJ 08536
B.5.3.4	Country	United States
B.5.4	Telephone number	+4570202728
B.5.6	E-mail	clinicaltrials@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	HexaBody®-CD38
D.3.2	Product code	GEN3014
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	GEN3014
D.3.9.1	CAS number	2430792-01-9
D.3.9.2	Current sponsor code	HexaBody®-CD38
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	Yes
D.3.11.13.1	Other medicinal product type	Human monoclonal antibody
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	Yes
D.2.1.1.1	Trade name	DARZALEX 1800 mg solution for injection
D.2.1.1.2	Name of the Marketing Authorisation holder	Janssen-Cilag International NV
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/13/1153
D.3 Description of the IMP
D.3.4	Pharmaceutical form	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	Daratumumab
D.3.9.1	CAS number	945721-28-8
D.3.9.3	Other descriptive name	HUMAX-CD38
D.3.9.4	EV Substance Code	SUB175772
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	120
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	Yes
D.3.11.13.1	Other medicinal product type	Human monoclonal antibody

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

Relapsed or Refractory Multiple Myeloma and Other Hematologic Malignancies

E.1.1.1

Medical condition in easily understood language

Relapsed or Refractory Multiple Myeloma and Other Hematologic Malignancies

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	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10066481
E.1.2	Term	Hematological malignancy
E.1.2	System Organ Class	100000004864

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	10028228
E.1.2	Term	Multiple myeloma
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

- Determine the RP2D and if reached, the MTD of GEN3014
- Evaluate the safety and tolerability of GEN3014

Please refer to the protocol section 2 (Tables 2-2 and 2-3) for the full list of main objectives for the Expansion Part A (GEN3014 Single Cohorts) and Expansion Part B (Randomized H2H) of the study, respectively.

E.2.2

Secondary objectives of the trial

- Characterize the PK properties of GEN3014
- Characterize the pharmacodynamic properties of GEN3014
- Evaluate immunogenicity
- Assess the preliminary anti-tumor activity of GEN3014
- Assess the clinical efficacy of GEN3014

Please refer to the protocol section 2 (Tables 2-2 and 2-3) for the full list of secondary objectives for the Expansion Part A (GEN3014 Single Cohorts) and Expansion Part B (Randomized H2H) of the study, respectively.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Must be at least 18 years of age.
2. Must sign an informed consent form (ICF) prior to any Screening procedures. Where required by local or country specific regulations, each subject must sign a separate ICF if he or she agrees to provide samples for genomic biomarker analysis (deoxyribonucleic acid [DNA] and ribonucleic acid [RNA]).
3. Must have fresh bone marrow samples collected at Screening.
4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) score 0, 1, or 2.
5. Has acceptable laboratory test results during the Screening period
6. A woman of reproductive potential must agree to use adequate contraception during the trial and for 12 months after the last GEN3014 administration. Adequate contraception is defined as highly effective methods of contraception (refer to Appendix 10.4 for more information). In countries where 2 highly effective methods of contraception are required, both methods will be required for inclusion.
7. A woman of childbearing potential must have a negative serum beta-human chorionic gonadotropin (β-hCG) at Screening.
8. A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the trial and for 12 months after receiving the last dose of GEN3014.
9. 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, eg, either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, and all men must also not donate sperm during the trial and for 12 months after receiving the last dose of GEN3014.

Specific Inclusion Criteria for RRMM:
10. Must have documented multiple myeloma as defined by the criteria below and have evidence of disease progression on the most recent prior treatment regimen based on IMWG criteria:
• Prior documentation of monoclonal plasma cells in the bone marrow ≥10% or presence of a biopsy-proven plasmacytoma and
• Measurable disease at baseline as defined by any of the following:
- IgG, IgA, IgD, or IgM myeloma: Serum M-protein level ≥0.5 g/dL (≥5 g/L) or urine M-protein level ≥200 mg/24 hours;
or
- Light chain myeloma: Serum Ig free light chain (FLC) ≥10 mg/dL and abnormal serum Ig kappa lambda FLC ratio
11. For anti-CD38 mAb-naive RRMM subjects: Subject received at least 3 prior lines of therapy including a PI and an IMiD in any order, or is double refractory to a PI and an IMiD; or subject received ≥ 2 prior lines of therapy if 1 of those lines included a combination of PI and IMiD. Note: Subjects should not have received any anti-CD38 antibody. Anti-CD38 mAb-naive subjects with RRMM may be recruited from Sweden, France, Spain, Netherlands, and Australia, and from countries where anti-CD38 therapies are not available.
12. For anti-CD38 mAb-treated RRMM subjects: Subject has received at least 2 prior lines of therapy and must have discontinued daratumumab or isatuximab for at least 4 weeks prior to the first dose of GEN3014. Note: Subjects should not have received any other anti-CD38 antibody except daratumumab or isatuximab.
13. Potassium level ≥3.0 mEq/L (≥3.0 mmol/L); and corrected serum calcium ≤14.0 mg/dL (≤3.5 mmol/L) or free ionized calcium ≤6.5 mg/dL (≤1.6 mmol/L).

Specific Inclusion Criteria for R/R AML:
14. Relapsed or refractory AML, both de novo or secondary; must have failed all conventional therapy. Acute promyelocytic leukemia (APL) is excluded from this trial. Note: Relapse is defined by BM blasts ≥5% in patients who have been in complete remission (CR) previously, or reappearance of blasts in the blood, or development of extramedullary AML. Refractory is defined as not being able to achieve a CR after the initial therapy.
15. Subject with relapsed AML who received at least 2 prior therapies for AML with the exception of hydroxyurea.
16. Subject with refractory AML who received at least 1 prior line of therapy for AML with the exception of hydroxyurea.
17. Subject's life expectancy at Screening is judged to be at least 3 months.

Please refer to Protocol sections 4.1.2 and 4.1.3 for the Inclusion Criteria for the Expansion Part A (GEN3014 Single Cohorts) and Expansion Part B (Randomized H2H), respectively

E.4

Principal exclusion criteria

Exclusion Criteria (Dose Escalation and Expansion Part A [GEN3014 Single Cohorts])

1. Prior treatment with any anti-CD38 directed therapies (eg. daratumumab, isatuximab, CD38 CAR-T, bispecific Ab) in anti-CD38 mAb- naive RRMM Cohort. Note: Prior daratumumab or isatuximab exposure is allowed for anti-CD38 mAb-treated RRMM subjects in the Dose Escalation and anti-CD38 mAb-refractory RRMM Cohort in the Expansion Part A.
2. Treatment with an anti-cancer agent (eg, small molecule, antibody, CAR-T cell therapy), chemotherapy, radiation therapy, or major surgery within 2 weeks prior to the first dose of GEN3014.
3. Treatment with an investigational drug within 4 weeks or 5 half-lives, whichever is shorter, prior to the first dose of GEN3014.
4. Cumulative dose of corticosteroids more than the equivalent of ≥140 mg of prednisone within 2-week period before the first dose of GEN3014.
5. Has clinically significant cardiac disease, including:
• Myocardial infarction within 1 year prior to the first dose of GEN3014, or unstable or uncontrolled disease/condition related to or affecting cardiac function (eg, unstable angina, congestive heart failure, New York Heart Association Class III-IV [see Appendix 10.6]) uncontrolled cardiac arrhythmia (CTCAE v5.0 grade 2 or higher) or clinically significant electrocardiogram (ECG) abnormalities.
• Screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia’s formula (QTcF) >480 msec.
6. Toxicities from previous anti-cancer therapies have not resolved to baseline levels or to Grade 1 or less except for alopecia and peripheral neuropathy.
7. Primary central nervous system (CNS) tumor or known CNS involvement at Screening.
8. Has known history/positive serology for hepatitis B (unless immune due to vaccination or unless passive immunization due to Ig therapy):
• Positive test for antibodies to the hepatitis B core antigen (anti-HBc) and
• Negative test for antibodies to the hepatitis B surface antigen (anti-HBs).
9. Known medical history or ongoing hepatitis C infection that has not been cured.
10. Known history of seropositivity of human immunodeficiency virus (HIV).
11. Currently receiving any other investigational agents.
12. 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 GEN3014.
13. A man who plans to father a child while enrolled in this trial or within 12 months after the last dose of GEN3014.

Specific Exclusion Criteria for RRMM:
14. Prior allogeneic HSCT.
15. Autologous HSCT within 3 months of the first dose of GEN3014.

Specific Exclusion Criteria for R/R AML:
16. <5% blasts in blood or bone marrow at Screening.
17. Prior autologous HSCT.
18. Allogenic HSCT within 3 months of the first dose of GEN3014.
19. Active graft-versus-host-disease requiring immunosuppressive treatment. Any immunosuppressive medication (eg, calcineurin inhibitors) must be stopped ≥4 weeks prior to the first dose of GEN3014.

Please refer to the protocol section 4.2.2 for the full list of Exclusion criteria for the Expansion Part B (Randomized H2H).

E.5 End points

E.5.1

Primary end point(s)

- Incidence of DLTs
- Safety: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), including changes in laboratory values, vital signs, electrocardiograms (ECGs)
- Tolerability: Dose interruptions, delay, and dose intensity.

Please refer to the protocol section 2 (Tables 2-2 and 2-3) for the full list of primary endpoints for the Expansion Part A (GEN3014 Single Cohorts) and Expansion Part B (Randomized H2H) of the study, respectively.

E.5.1.1

Timepoint(s) of evaluation of this end point

According to Protocol

E.5.2

Secondary end point(s)

• Noncompartmental PK parameters (if feasible):
o Maximum concentration (Cmax)
o Time to Cmax (Tmax)
o Predose concentration (Ctrough)
o Area under the concentration-time curve from time zero to last quantifiable sample (AUC0-last) and from time zero to 168 h (AUC0-168h)
o Accumulation ratios in Cmax (RA,Cmax) and AUC (RA,AUC]
• In addition, a population PK modeling approach may be employed
• Pharmacodynamic markers in blood and tumor samples, including frequencies of Natural Killer (NK) cells and other leukocyte subsets and complement analyses
• Anti-GEN3014 antibodies
• Objective response rate (ORR)
• Clinical benefit rate (CBR)
• Duration of response (DOR)
• Time-to-response (TTR)
• Progression-free survival (PFS)
• Overall survival (OS)

Please refer to the protocol section 2 (Tables 2-2 and 2-3) for the full list of secondary endpoints for the Expansion Part A (GEN3014 Single Cohorts) and Expansion Part B (Randomized H2H) of the study, respectively.

E.5.2.1

Timepoint(s) of evaluation of this end point

According 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

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Tolerability and Immunogenicity

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

Yes

E.7.1.3.1

Other trial type description

Dose escalation

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

Yes

E.8.1.1

Randomised

Yes

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

Yes

E.8.1.7.1

Other trial design description

Randomized for Expansion Part B (Randomized H2H)

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

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

Korea, Republic of

United States

France

Poland

Sweden

Netherlands

Spain

Czechia

Greece

Denmark

Hungary

Russian Federation

Turkey

Ukraine

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:

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

152

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)

Not Applicable

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

2023-01-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2023-01-16

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

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