GEN3014 Trial in Relapsed or Refractory Hematologic Malignancies
NCT ID: NCT04824794
Last Updated: 2025-12-22
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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TERMINATED
PHASE1/PHASE2
130 participants
INTERVENTIONAL
2021-03-09
2025-07-31
Brief Summary
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1. The Dose Escalation will test increasing doses of GEN3014 to identify 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.
3. Expansion Part B will compare intravenous (IV) GEN3014 with the subcutaneous (SC) daratumumab in ex-US countries.
Participants will receive either GEN3014 into the vein or daratumumab under the skin; 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.
Detailed Description
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In the dose escalation phase GEN3014 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. 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.
Conditions
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Keywords
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Study Design
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RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
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GEN3014
Experimental: GEN3014 Participants in Dose Escalation phase with
* RRMM
* R/R AML
Participants in Expansion Part A with
* RRMM (anti-CD38 mAb-naïve)
* RRMM (anti-CD38 mAb-refractory)
* R/R DLBCL
* R/R AML
Participants in Expansion Part B with
• RRMM (anti-CD38 mAb-naïve)
GEN3014
GEN3014 is administered by IV infusion.
Daratumumab
Participants in Expansion Part B with
\- RRMM (anti-CD38 mAb-naïve)
Daratumumab
Daratumumab is administered by SC injections.
Interventions
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GEN3014
GEN3014 is administered by IV infusion.
Daratumumab
Daratumumab is administered by SC injections.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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 participants 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.
Exclusion Criteria
* 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.
* Prior allogeneic hematopoietic stem cell transplant (HSCT).
* Autologous HSCT within 3 months of the first dose of GEN3014.
* \<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.
18 Years
ALL
No
Sponsors
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Genmab
INDUSTRY
Responsible Party
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Principal Investigators
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Study Official
Role: STUDY_DIRECTOR
Genmab
Locations
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John Theurer Cancer Center
Hackensack, New Jersey, United States
University Hospitals Cleveland Medical Center
Cleveland, Ohio, United States
Medical college of Wisconsin
Milwaukee, Wisconsin, 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
New Town, , 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
Rio, , Greece
Ahepa University General hospital
Thessaloniki, , Greece
Szabolcs-Szatmar-Bereg County Hospitals and University Hospital, Josa Andras University Hospital
Nyíregyháza, , Hungary
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
Maastricht UMC
Maastricht, , Netherlands
Erasmus MC
Rotterdam, , Netherlands
UMC Utrecht
Utrecht, , Netherlands
Christchurch Hospital
Christchurch, , New Zealand
Auckland Cancer Trials Centre
Grafton, , New Zealand
Palmerston North Hospital
Palmerston North, , New Zealand
North Shore Hospital
Takapuna, , New Zealand
University Clinic of Hematology
Skopje, , North Macedonia
Makati Medical Center
Makati City, , Philippines
University Centrum Kliniczne
Gdansk, , Poland
Pratia Onkologia Katowice
Katowice, , Poland
Pratia MCM
Krakow, , Poland
Wroclaw Medical University
Wroclaw, , Poland
Chonnam National University Hwasun Hospital
Gwangju, , South Korea
Pusan National University Hospital PNUH
Pusan, , South Korea
Gachon University Gil Medical Center
Seongnam, , South Korea
Samsung Medical Center
Seoul, , South Korea
Seoul National University Hospital
Seoul, , South Korea
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
Countries
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Other Identifiers
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2020-003781-40
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
NL75422.056.21
Identifier Type: REGISTRY
Identifier Source: secondary_id
2023-507086-26-00
Identifier Type: CTIS
Identifier Source: secondary_id
GCT3014-01
Identifier Type: -
Identifier Source: org_study_id