Multiple Myeloma Clinical Trial

GEN3014 Safety Trial in Relapsed or Refractory Hematologic Malignancies

Summary

This trial is an open-label, safety trial of GEN3014 (HexaBody®-CD38). The trial consists of two parts: a dose escalation part phase 1, first-in-human (FIH), and an expansion part phase 2a.

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Full Description

This trial will be conducted in 3 parts: Dose Escalation (phase 1), Expansion Parts, A and B (phase 2).

In the dose escalation phase GEN314 will be evaluated in RRMM and relapsed and refractory acute myeloid leukemia (R/R AML). The participants will receive GEN3014 administered at various dose levels in 28 day cycles. Dose Limiting Toxicities (DLTs) will be assessed during the first treatment cycle and the Maximum Tolerated Dose (MTD) and/or Recommended phase 2 dose (RP2D) will be determined.

In Expansion Part A, GEN3014 will be further evaluated in 4 cohorts: anti-CD38 monoclonal antibody (mAb)-naive RRMM, anti-CD38 mAb-refractory RRMM, relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL), and R/R AML at the RP2D identified from the Dose Escalation per protocol. In Expansion Part B, GEN3014 IV will be compared to daratumumab SC, head-to-head (H2H) to evaluate whether GEN3014 may be more potent in anti-CD38 mAb-naïve RRMM participants.

View Eligibility Criteria

Eligibility 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 (β-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 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 is for people with:

Multiple Myeloma

Phase:

Phase 1

Estimated Enrollment:

252

Study ID:

NCT04824794

Recruitment Status:

Recruiting

Sponsor:

Genmab

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There are 3 Locations for this study

See Locations Near You

John Theurer Cancer Center
Hackensack New Jersey, 07601, United States
University Hospitals Cleveland Medical Center
Cleveland Ohio, 44106, United States
Medical college of Wisconsin
Milwaukee Wisconsin, 53226, United States
Northern Health
Epping , , Australia
The Alfred Hospital
Melbourne , , Australia
Royal Prince Alfred Hospital
Sydney , , Australia
University Clinical Center of the Republic of the Srpska
Banja Luka , , Bosnia and Herzegovina
Klinika za hematologiju KCUS
Sarajevo , , Bosnia and Herzegovina
UKC - University Clinical Center Tuzla
Tuzla , , Bosnia and Herzegovina
Fakultni Nemocnice Brno
Brno , , Czechia
Vseobecna fakultni nemocnice
Nové Město , , Czechia
Fakultni Nemocnice Hradec Kralove FNHK
Nový Hradec Králové , , Czechia
Fakultni Nemocnice Olomouc (FNOL)
Olomouc , , Czechia
FNO - Fakultni nemocnice Ostrava
Poruba , , Czechia
Aalborg Universitet
Aalborg , , Denmark
Vejle Hospital
Vejle , , Denmark
CHRU de Lille
Lille , , France
CHRU de Nantes
Nantes , , France
ARENSIA Exploratory Medicine LLC
Tbilisi , , Georgia
Alexandra General Hospital
Athens , , Greece
Evangelismos Hospital NKUA
Athens , , Greece
University General Hospital of Patras
Río , , Greece
Ahepa University General hospital
Thessaloníki , , Greece
Szabolcs-Szatmar-Bereg County Hospitals and University Hospital, Josa Andras University Hospital
Nyíregyháza , , Hungary
Chonnam National University Hwasun Hospital
Gwangju , , Korea, Republic of
Pusan National University Hospital PNUH
Pusan , , Korea, Republic of
Gachon University Gil Medical Center
Seongnam , , Korea, Republic of
Samsung Medical Center
Seoul , , Korea, Republic of
Seoul National University Hospital
Seoul , , Korea, Republic of
Hospital Ampang
Ampang , , Malaysia
Hospital Sultanah Aminah
Johor Bahru , , Malaysia
Hospital Umum Sarawak
Kuching , , Malaysia
Beacon Hospital
Petaling Jaya , , Malaysia
Institute of Oncology, ARENSIA Exploratory Medicine
Chisinau , , Moldova, Republic of
Maastricht UMC
Maastricht , , Netherlands
Erasmus MC
Rotterdam , , Netherlands
UMC Utrecht
Utrecht , , Netherlands
Christchurch Hospital
Christchurch , , New Zealand
Auckland Cancer Trials Centre
Grafton , , New Zealand
University Clinic of Hematology
Skopje , , North Macedonia
University Centrum Kliniczne
Gdańsk , , Poland
Pratia Onkologia Katowice
Katowice , , Poland
Pratia MCM
Kraków , , Poland
Wroclaw Medical University
Wrocław , , Poland
University of Navarra
Pamplona , , Spain
University Hospital of Salamanca
Salamanca , , Spain
Karolinska Institute
Huddinge , , Sweden
Universitetssjukhuset i Lund
Lund , , Sweden
Arensia Exploratory Medicine
Kyiv , , Ukraine

How clear is this clinincal trial information?

Study is for people with:

Multiple Myeloma

Phase:

Phase 1

Estimated Enrollment:

252

Study ID:

NCT04824794

Recruitment Status:

Recruiting

Sponsor:


Genmab

How clear is this clinincal trial information?

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