ANZCTR - Registration

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers

Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04824794

Registration number

NCT04824794

Ethics application status

Date submitted

9/03/2021

Date registered

1/04/2021

Date last updated

31/10/2024

Titles & IDs

Public title

GEN3014 Safety Trial in Relapsed or Refractory Hematologic Malignancies

Scientific title

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

Secondary ID [1]

2020-003781-40

Secondary ID [2]

GCT3014-01

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Relapsed or Refractory Multiple Myeloma (RRMM)

Diffuse Large B Cell Lymphoma (DLBCL)

Acute Myeloid Leukemia (AML)

Condition category

Condition code

Cancer

Other cancer types

Cancer

Leukaemia - Acute leukaemia

Cancer

Children's - Leukaemia & Lymphoma

Cancer

Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma

Cancer

Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Cancer

Leukaemia - Chronic leukaemia

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Treatment: Other - GEN3014
Treatment: Drugs - Daratumumab

Experimental: GEN3014 - Experimental: GEN3014 Participants in Dose Escalation phase with

* Relapsed or refractory myeloid myeloma (RRMM)
* R/R acute myeloid leukemia (AML)

Participants in Expansion Part A with

* RRMM (anti-CD38 mAb-naïve)
* RRMM (anti-CD38 mAb-refractory)
* R/R diffuse large B-cell lymphoma (DLBCL)
* R/R AML

Participants in Expansion Part B with

• RRMM (anti-CD38 mAb-naïve)

Active comparator: Daratumumab - Participants in Expansion Part B with

- RRMM (anti-CD38 mAb-naïve)

Treatment: Other: GEN3014
GEN3014 is administered by IV infusion.

Treatment: Drugs: Daratumumab
Daratumumab is administered by SC injections.

Intervention code [1]

Treatment: Other

Intervention code [2]

Treatment: Drugs

Comparator / control treatment

Control group

Outcomes

Primary outcome [1]

Dose Escalation: Number of Participants with Dose Limiting Toxicities (DLTs)

Timepoint [1]

Up to 28 days during the first cycle

Primary outcome [2]

Dose Escalation: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

Timepoint [2]

From first dose until the end of the safety follow-up period (30 days after last dose)

Primary outcome [3]

Expansion Part A: Objective Response Rate (ORR) of GEN3014

Timepoint [3]

Up to 8 years

Primary outcome [4]

Expansion Part B: Objective Response Rate (ORR) of GEN3014 IV vs Daratumumab SC in Anti-CD38 mAb-naive RRMM Participants

Timepoint [4]

Up to 8 years

Secondary outcome [1]

Dose Escalation: Maximum (peak) Plasma Concentration (Cmax) of GEN3014

Timepoint [1]

Predose and postdose at multiple timepoints up to Cycle 6 (Cycle length=28 days); Pre-dose and 5 minutes post end of infusion from Cycle 7 and beyond (Up to 8 years)

Secondary outcome [2]

Dose Escalation: Time to Reach Cmax (Tmax) of GEN3014

Timepoint [2]

Predose and postdose at multiple timepoints up to Cycle 6 (Cycle length=28 days); Pre-dose and 5 minutes post end of infusion from Cycle 7 and beyond (Up to 8 years)

Secondary outcome [3]

Dose Escalation: Pre-dose (trough) Concentrations (Ctrough) of GEN3014

Timepoint [3]

Predose and postdose at multiple timepoints of each Cycle (Cycle length=28 days)

Secondary outcome [4]

Dose Escalation: Area Under the Concentration Time Curve From Zero to Last Quantifiable Sample (AUC0-last)

Timepoint [4]

Predose and postdose at multiple timepoints up to Cycle 6 (Cycle length=28 days); Pre-dose and 5 minutes post end of infusion from Cycle 7 and beyond (Up to 8 years)

Secondary outcome [5]

Dose Escalation: Area Under the Concentration Time Curve From Zero to 168 hours (AUC0-168 h)

Timepoint [5]

Predose and postdose at multiple timepoints up to Cycle 6 (Cycle length=28 days); Pre-dose and 5 minutes post end of infusion from Cycle 7 and beyond (Up to 8 years)

Secondary outcome [6]

Dose Escalation: Accumulation Ratio in Cmax (RA, Cmax)

Timepoint [6]

Predose and postdose at multiple timepoints up to Cycle 6 (Cycle length=28 days); Pre-dose and 5 minutes post end of infusion from Cycle 7 and beyond (Up to 8 years)

Secondary outcome [7]

Dose Escalation: Accumulation Ratio in AUC (RA, AUC)

Timepoint [7]

Predose and postdose at multiple timepoints up to Cycle 6 (Cycle length=28 days); Pre-dose and 5 minutes post end of infusion from Cycle 7 and beyond (Up to 8 years)

Secondary outcome [8]

Dose Escalation: Number of Participants with Anti-Drug Antibody (ADA) of GEN3014

Timepoint [8]

From first dose until treatment discontinuation (Up to 8 years)

Secondary outcome [9]

Dose Escalation: Objective Response Rate (ORR) of GEN3014

Timepoint [9]

Up to 8 years

Secondary outcome [10]

Dose Escalation: Clinical Benefit Rate (CBR) of GEN3014

Timepoint [10]

Up to 8 years

Secondary outcome [11]

Dose Escalation: Duration of Response (DOR) of GEN3014

Timepoint [11]

Up to 8 years

Secondary outcome [12]

Dose Escalation: Time-to-response (TTR) of GEN3014

Timepoint [12]

Up to 8 years

Secondary outcome [13]

Dose Escalation: Progression-free survival (PFS) of GEN3014

Timepoint [13]

Up to 8 years

Secondary outcome [14]

Dose Escalation: Overall Survival (OS) of GEN3014

Timepoint [14]

Up to 8 years

Secondary outcome [15]

Expansion Part A: Clinical Benefit Rate (CBR) of GEN3014

Timepoint [15]

Up to 8 years

Secondary outcome [16]

Expansion Part A: Duration of Response (DOR) of GEN3014

Timepoint [16]

Up to 8 years

Secondary outcome [17]

Expansion Part A: Time-to-response (TTR) of GEN3014

Timepoint [17]

Up to 8 years

Secondary outcome [18]

Expansion Part A: Progression-free survival (PFS) of GEN3014

Timepoint [18]

Up to 8 years

Secondary outcome [19]

Expansion Part A: Overall Survival (OS) of GEN3014

Timepoint [19]

Up to 8 years

Secondary outcome [20]

Expansion Part A: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) per CTCAE Version 5.0

Timepoint [20]

From first dose until the end of the safety follow-up period (30 days after last dose)

Secondary outcome [21]

Expansion Part A: Number of Participants with Anti-Drug Antibody (ADA) of GEN3014

Timepoint [21]

From first dose until treatment discontinuation (Up to 8 years)

Secondary outcome [22]

Expansion Part A: Maximum (peak) Plasma Concentration (Cmax) of GEN3014

Timepoint [22]

Predose and postdose at multiple timepoints up to Cycle 6 (Cycle length=28 days); Pre-dose and 5 minutes post end of infusion from Cycle 7 and beyond (Up to 8 years)

Secondary outcome [23]

Expansion Part A: Time to Reach Cmax (Tmax) of GEN3014

Timepoint [23]

Predose and postdose at multiple timepoints up to Cycle 6 (Cycle length=28 days); Pre-dose and 5 minutes post end of infusion from Cycle 7 and beyond (Up to 8 years)

Secondary outcome [24]

Expansion Part A: Pre-dose (trough) Concentrations (Ctrough) of GEN3014

Timepoint [24]

Predose and postdose at multiple timepoints of each Cycle (Cycle length=28 days)

Secondary outcome [25]

Expansion Part A: Area Under the Concentration Time Curve From Zero to Last Quantifiable Sample (AUC0-last)

Timepoint [25]

Predose and postdose at multiple timepoints up to Cycle 6 (Cycle length=28 days); Pre-dose and 5 minutes post end of infusion from Cycle 7 and beyond (Up to 8 years)

Secondary outcome [26]

Expansion Part A: Area Under the Concentration Time Curve From Zero to 168 hours (AUC0-168 h)

Timepoint [26]

Predose and postdose at multiple timepoints up to Cycle 6 (Cycle length=28 days); Pre-dose and 5 minutes post end of infusion from Cycle 7 and beyond (Up to 8 years)

Secondary outcome [27]

Expansion Part A: Accumulation Ratio in Cmax (RA, Cmax)

Timepoint [27]

Predose and postdose at multiple timepoints up to Cycle 6 (Cycle length=28 days); Pre-dose and 5 minutes post end of infusion from Cycle 7 and beyond (Up to 8 years)

Secondary outcome [28]

Expansion Part A: Accumulation Ratio in AUC (RA, AUC)

Timepoint [28]

Predose and postdose at multiple timepoints up to Cycle 6 (Cycle length=28 days); Pre-dose and 5 minutes post end of infusion from Cycle 7 and beyond (Up to 8 years)

Secondary outcome [29]

Expansion Part A: Accumulation Ratio in Ctrough (RA,Ctrough)

Timepoint [29]

Predose and postdose at multiple timepoints up to Cycle 6 (Cycle length=28 days); Pre-dose and 5 minutes post end of infusion from Cycle 7 and beyond (Up to 8 years)

Secondary outcome [30]

Expansion Part B: Ctrough Levels of GEN3014 IV or Daratumumab SC on Cycle 3 Day 1

Timepoint [30]

Cycle 3 Day 1

Secondary outcome [31]

Expansion Part B: Very Good Partial Response (VGPR), or better of GEN3014 IV vs Daratumumab SC

Timepoint [31]

Up to 8 years

Secondary outcome [32]

Expansion Part B: Complete Response (CR) or better of GEN3014 IV vs Daratumumab SC

Timepoint [32]

Up to 8 years

Secondary outcome [33]

Expansion Part B: Duration of Response (DOR) of GEN3014 IV vs Daratumumab SC

Timepoint [33]

Up to 8 years

Secondary outcome [34]

Expansion Part B: Time-to-response (TTR) of GEN3014 IV vs Daratumumab SC

Timepoint [34]

Up to 8 years

Secondary outcome [35]

Expansion Part B: Progression-free Survival (PFS) of GEN3014 IV vs Daratumumab SC

Timepoint [35]

Up to 8 years

Secondary outcome [36]

Expansion Part B: Overall Survival (OS) of GEN3014 IV vs Daratumumab SC

Timepoint [36]

Up to 8 years

Secondary outcome [37]

Expansion Part B: Time to Next Therapy (TTNT)

Timepoint [37]

Up to 8 years

Secondary outcome [38]

Expansion Part B: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) per CTCAE Version 5.0

Timepoint [38]

From first dose until the end of the safety follow-up period (30 days after last dose)

Secondary outcome [39]

Expansion Part B: Number of Participants with Anti-Drug Antibody (ADA) of GEN3014, Anti-daratumumab Antibodies and Anti-recombinant Human Hyaluronidase PH20 (rHuPH20)

Timepoint [39]

From first dose until treatment discontinuation (Up to 8 years)

Eligibility

Key inclusion criteria

Key Inclusion Criteria

* Must have fresh bone marrow samples collected at Screening for RRMM, R/R AML, and R/R DLBCL with suspected bone marrow involvement.
* Dose Escalation phase, Expansion Part A (for MM and AML) and Expansion Part B- Eastern Cooperative Oncology Group (ECOG) performance status (PS) score 0, 1, or 2. Expansion Part A (for DLBCL): ECOG PS 0 or 1.
* Has acceptable laboratory test results during the Screening period.
* A woman of reproductive potential must agree to use adequate contraception during the trial and for 12 months after the last GEN3014 or daratumumab SC administration.
* A woman of childbearing potential must have a negative serum beta-human chorionic gonadotropin (ß-hCG) at Screening and additionally, for Expansion Part B, within 72 hours of the first dose of study treatment prior to dosing.
* A woman must agree not to donate eggs (ova, oocytes) for assisted reproduction during the trial and for 12 months after receiving the last dose of GEN3014 or daratumumab SC.
* 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 and all men must not donate sperm during the trial and for 12 months after receiving the last dose of GEN3014 or daratumumab SC.

Specific for RRMM:

* 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:

* Immunoglobulin (Ig) G, 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.

Note: Participants with RRMM must have exhausted standard therapies, at the investigator's discretion.

* For anti-CD38 mAb-naive RRMM Cohort: Participant received at least 3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory imide drug (IMiD) in any order, or is double refractory to a PI and an IMiD; or participant received = 2 prior lines of therapy if 1 of those lines included a combination of PI and IMiD. Note: Participants should not have received any anti-CD38 antibody.
* Anti-CD38 mAb-naive RRMM participants will be enrolled from ex-US countries.
* Dose Escalation phase - For anti-CD38 mAb-treated RRMM Cohort: Participant 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: Participants should not have received any other anti-CD38 antibody except daratumumab or isatuximab.

Specific for R/R AML:

* 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 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.
* Participant with relapsed AML who received at least 2 prior therapies for AML with the exception of hydroxyurea.
* Participant with refractory AML who received at least 1 prior line of therapy for AML with the exception of hydroxyurea.
* Participant's life expectancy at Screening is judged to be at least 3 months.

Specific for DLBCL:

* Expansion phase: Relapsed or refractory DLBCL, both de novo or histologically transformed. Participants with R/R DLBCL must have exhausted standard therapies, at the investigator's discretion.
* Expansion phase: Received at least 2 prior lines of systemic therapy, with 1 being a CD20-containing chemoimmunotherapy.
* Expansion phase: Have at least 1 measurable site of disease as per Lugano criteria.
* Expansion phase: Must have available archival or fresh tumor tissue or both to submit to a central laboratory for CD38 assay.

Key

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Exclusion Criteria

* Prior treatment with any CD38-directed therapies (eg, daratumumab, isatuximab, CD38 chimeric antigen receptor T cell (CAR-T), bispecific antibody (Ab)) in anti-CD38 mAb-naive RRMM Cohort. Note: Prior daratumumab or isatuximab exposure is allowed for anti-CD38 mAb-treated RRMM participants in the Dose Escalation and anti-CD38 mAb-refractory RRMM Cohort in the Expansion Part A.
* Treatment with an anti-cancer agent, chemotherapy, radiation therapy, or major surgery within 2 weeks prior to the first dose of study treatment (Dose Escalation and Expansion Part A) or randomization (Expansion Part B).
* Treatment with an investigational drug within 4 weeks or 5 half-lives, whichever is shorter, prior to the first dose of study treatment (Dose Escalation and Expansion Part A) or randomization (Expansion Part B).
* Cumulative dose of corticosteroids more than the equivalent of =140 mg of prednisone within 2-week period before the first dose of study treatment (Dose Escalation and Expansion Part A) or maximum cumulative dose of dexamethasone 160 mg within 28 days of randomization (Expansion Part B).
* Has clinically significant cardiac disease.
* Toxicities from previous anti-cancer therapies have not resolved to baseline levels or to Grade 1 or less except for alopecia and peripheral neuropathy.
* Primary central nervous system (CNS) tumor or known CNS involvement at Screening.
* Has known history/positive serology for hepatitis B.
* Known medical history or ongoing hepatitis C infection that has not been cured.
* Known history of seropositivity of human immunodeficiency virus (HIV) (Dose Escalation and Expansion Part A) or to be positive for HIV with details in the protocol (Expansion Part B).
* Currently receiving any other investigational agents.
* 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 study treatment.
* A man who plans to father a child while enrolled in this trial or within 12 months after the last dose of study treatment.

Specific Exclusion Criteria for RRMM:

* Prior allogeneic hematopoietic stem cell transplant (HSCT).
* Autologous HSCT within 3 months of the first dose of GEN3014.

Specific Exclusion Criteria for R/R AML:

* <5% blasts in blood or bone marrow at Screening.
* White blood cell (WBC) counts =50,000/microliter (µL) in peripheral blood that cannot be controlled by hydroxyurea prior to the first dose of GEN3014.
* Prior autologous HSCT.
* Allogenic HSCT within 3 months of the first dose of GEN3014.
* 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.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Masking / blinding

Open (masking not used)

Who is / are masked / blinded?

Intervention assignment

Other

Other design features

Phase

Phase 1

Type of endpoint/s

Statistical methods / analysis

Recruitment

Recruitment status

Active, not recruiting

Data analysis

Reason for early stopping/withdrawal

Other reasons

Date of first participant enrolment

Anticipated

Actual

9/03/2021

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

31/12/2026

Actual

Sample size

Target

252

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

Recruitment hospital [1]

Northern Health - Epping

Recruitment hospital [2]

The Alfred Hospital - Melbourne

Recruitment hospital [3]

Royal Prince Alfred Hospital - Sydney

Recruitment postcode(s) [1]

- Epping

Recruitment postcode(s) [2]

- Melbourne

Recruitment postcode(s) [3]

- Sydney

Recruitment outside Australia

Country [1]

United States of America

State/province [1]

New Jersey

Country [2]

United States of America

State/province [2]

Ohio

Country [3]

United States of America

State/province [3]

Wisconsin

Country [4]

Bosnia and Herzegovina

State/province [4]

Banja Luka

Country [5]

Bosnia and Herzegovina

State/province [5]

Sarajevo

Country [6]

Bosnia and Herzegovina

State/province [6]

Tuzla

Country [7]

Czechia

State/province [7]

Brno

Country [8]

Czechia

State/province [8]

Nové Mesto

Country [9]

Czechia

State/province [9]

Nový Hradec Králové

Country [10]

Czechia

State/province [10]

Olomouc

Country [11]

Czechia

State/province [11]

Poruba

Country [12]

Denmark

State/province [12]

Aalborg

Country [13]

Denmark

State/province [13]

Vejle

Country [14]

France

State/province [14]

Lille

Country [15]

France

State/province [15]

Nantes

Country [16]

Georgia

State/province [16]

Tbilisi

Country [17]

Greece

State/province [17]

Athens

Country [18]

Greece

State/province [18]

Río

Country [19]

Greece

State/province [19]

Thessaloníki

Country [20]

Hungary

State/province [20]

Nyíregyháza

Country [21]

Korea, Republic of

State/province [21]

Gwangju

Country [22]

Korea, Republic of

State/province [22]

Pusan

Country [23]

Korea, Republic of

State/province [23]

Seongnam

Country [24]

Korea, Republic of

State/province [24]

Seoul

Country [25]

Malaysia

State/province [25]

Ampang

Country [26]

Malaysia

State/province [26]

Johor Bahru

Country [27]

Malaysia

State/province [27]

Kuching

Country [28]

Malaysia

State/province [28]

Petaling Jaya

Country [29]

Moldova, Republic of

State/province [29]

Chisinau

Country [30]

Netherlands

State/province [30]

Maastricht

Country [31]

Netherlands

State/province [31]

Rotterdam

Country [32]

Netherlands

State/province [32]

Utrecht

Country [33]

New Zealand

State/province [33]

Christchurch

Country [34]

New Zealand

State/province [34]

Grafton

Country [35]

New Zealand

State/province [35]

Palmerston North

Country [36]

New Zealand

State/province [36]

Takapuna

Country [37]

North Macedonia

State/province [37]

Skopje

Country [38]

Philippines

State/province [38]

Makati City

Country [39]

Poland

State/province [39]

Gdansk

Country [40]

Poland

State/province [40]

Katowice

Country [41]

Poland

State/province [41]

Kraków

Country [42]

Poland

State/province [42]

Wroclaw

Country [43]

Spain

State/province [43]

Pamplona

Country [44]

Spain

State/province [44]

Salamanca

Country [45]

Sweden

State/province [45]

Huddinge

Country [46]

Sweden

State/province [46]

Lund

Country [47]

Ukraine

State/province [47]

Kyiv

Funding & Sponsors

Primary sponsor type

Commercial sector/industry

Name

Genmab

Address

Country

Ethics approval

Ethics application status

Summary

Brief summary

The drug that will be investigated in the study is an antibody, GEN3014. Since this is the first study of GEN3014 in humans, the main purpose is to evaluate safety. Besides safety, the study will determine the recommended GEN3014 dose to be tested in a larger group of participants and assess preliminary clinical activity of GEN3014. GEN3014 will be studied in relapsed or refractory multiple myeloma (also known as RRMM) and other blood cancers. The study consists of 3 parts:

1. The Dose Escalation will test increasing doses of GEN3014 to find a safe dose level to be tested in the other two parts.
2. Expansion Part A will further test the GEN3014 dose determined from the Dose Escalation Part.
3. Expansion Part B will compare intravenous (IV) GEN3014 with the subcutaneous (SC) daratumumab in ex-US countries.

Participants will receive either GEN3014 or daratumumab; none will be given placebo. The study duration will be different for the individual participants. Overall, the study may be ongoing up to 5 years after the last participant's first treatment.

Trial website

https://clinicaltrials.gov/study/NCT04824794

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Study Official

Address

Genmab

Country

Phone

Fax

Contact person for public queries

Name

Genmab Trial Information

Address

Country

Phone

+45 70202728

Fax

[email protected]

Contact person for scientific queries

Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04824794

Trial Review

Registering a new trial?

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04824794