GEN3014 Trial in Relapsed or Refractory Hematologic Malignancies

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

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. In addition to 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 (disease has returned) or refractory (resistant to treatment) 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 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.

Study Overview

• Status: Terminated
• Conditions: Acute Myeloid Leukemia (AML); Diffuse Large B Cell Lymphoma (DLBCL); Relapsed or Refractory Multiple Myeloma (RRMM)
• Intervention / Treatment: Biological: GEN3014; Drug: Daratumumab

Detailed 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 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.

• Study Type: Interventional
• Enrollment (Actual): 130
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 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.

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Daratumumab; Participants in Expansion Part B with - RRMM (anti-CD38 mAb-naïve)	Drug: Daratumumab; Daratumumab is administered by SC injections.; Other Names: DARZALEX FASPRO®
Experimental: 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)	Biological: GEN3014; GEN3014 is administered by IV infusion.; Other Names: HexaBody®-CD38

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Escalation: Number of Participants With Dose Limiting Toxicities (DLTs)	DLTs were defined as: All Grade 5 toxicities, Grade 4 thrombocytopenia, neutropenia or anemia and Grade 3/4 febrile neutropenia and hemorrhage associated with thrombocytopenia, all non-hematological toxicities of grade ≥3 (with exceptions per protocol), Grade 4 tumor lysis syndrome (TLS), Grade 4 infusion-related reaction (IRR), and any liver toxicity of elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥3 times or greater above the upper limit of normal (ULN) with serum total bilirubin of ≥2 times the upper limit of normal, without findings of cholestasis and in the absence of alternative etiologies. DLTs were graded for severity according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0.	28 days during the first cycle (cycle =28 days)
Dose Escalation: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE was any untoward medical occurrence in a participant or clinical trial participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE was defined as an AE that met 1 of the following criteria: fatal or life-threatening, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect, was medically significant (jeopardized the participant or may have required medical or surgical intervention to prevent one of the outcomes listed above), required inpatient hospitalization or prolongation of existing hospitalization. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.	Up to approximately 4 years 3 months
Expansion Part A: Objective Response Rate (ORR)	ORR was defined as the percentage of participants with a partial response (PR) or better based on International Myeloma Working Group (IMWG) criteria for RRMM participants and based on Lugano criteria for DLBCL participants. Per IMWG criteria, PR was defined as ≥50% reduction of serum M-protein plus reduction in 24-h urinary M-protein by ≥90% or to <200 mg per 24 h. In addition to these criteria, if present at baseline, a ≥50% reduction in the size (sum of the product of the diameters [SPD]) of soft tissue plasmacytomas was also required. Per Lugano criteria, PR was defined as ≥50% decrease in SPD of up to 6 target measurable nodes and extranodal sites, absent/normal, regressed, but no increase in non-measurable lesions, spleen regressed >50% in length beyond normal (13 centimeters [cm]), and no new lesions.	Up to approximately 4 years 3 months
Expansion Part B: ORR	ORR was defined as the percentage of participants with a PR or better based on IMWG criteria. Per IMWG criteria, PR was defined as ≥50% reduction of serum M-protein plus reduction in 24-h urinary M-protein by ≥90% or to <200 mg per 24 h. In addition to these criteria, if present at baseline, a ≥50% reduction in the size (SPD) of soft tissue plasmacytomas was also required.	Up to approximately 4 years 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Escalation and Expansion Part A: Maximum (Peak) Plasma Concentration (Cmax) of GEN3014	Venous blood samples were collected for analyzing concentrations of GEN3014. For the RRMM Dose Escalation 0.2/0.6 mg/kg arm, the participant underwent intraparticipant dose escalation in Cycle 1, where the participant received 0.2 mg/kg during the first week and 0.6 mg/kg from second week and beyond. Therefore, pharmacokinetic (PK) parameters were additionally calculated for Cycle 1 Day 8 dosing only in the RRMM Dose Escalation 0.2/0.6 mg/kg arm to account for the change in dosing over Cycle 1 in this arm.	Dose Escalation: Cycle 1 Day 1, Cycle 1 Day 8 (RRMM Dose Escalation: GEN3014 0.2/0.6 mg/kg only), Cycle 2 Day 1, Expansion Part A: Cycle 1 Day 1, Cycle 2 Day 1 (cycle =28 days)
Dose Escalation, Expansion Part A and Expansion Part B: Pre-dose (Trough) Concentrations (Ctrough) of GEN3014	Venous blood samples were collected for analyzing concentrations of GEN3014. For the RRMM Dose Escalation 0.2/0.6 mg/kg arm, the participant underwent intraparticipant dose escalation in Cycle 1, where the participant received 0.2 mg/kg during the first week and 0.6 mg/kg from second week and beyond. Therefore, PK parameters were additionally calculated for Cycle 1 Day 8 dosing in the RRMM Dose Escalation 0.2/0.6 mg/kg arm to account for the change in dosing over Cycle 1 in this arm.	Dose Escalation: Cycle (C) 1 Day (D) 1, C1D8 (RRMM GEN3014 0.2/0.6 mg/kg, R/R AML Dose Escalation), C2D1, Expansion Part A: C1D1, C2D1 (R/R DLBCL Expansion Part A: C1D8 and C2D8) Expansion Part B: C1D1, C1D8, C2D1, C3D1, C7D1, C8D1 (cycle = 28 days)
Dose Escalation and Expansion Part A: Area Under the Concentration Time Curve From Zero to Last Quantifiable Sample (AUC0-last) of GEN3014	Venous blood samples were collected for analyzing concentrations of GEN3014. For the RRMM Dose Escalation 0.2/0.6 mg/kg arm, the participant underwent intraparticipant dose escalation in Cycle 1, where the participant received 0.2 mg/kg during the first week and 0.6 mg/kg from second week and beyond. Therefore, PK parameters were additionally calculated for Cycle 1 Day 8 dosing only in the RRMM Dose Escalation 0.2/0.6 mg/kg arm to account for the change in dosing over Cycle 1 in this arm.	Dose Escalation: Cycle 1 Day 1, Cycle 1 Day 8 (RRMM Dose Escalation: GEN3014 0.2/0.6 mg/kg only), Cycle 2 Day 1, Expansion Part A: Cycle 1 Day 1, Cycle 2 Day 1 (cycle =28 days)
Dose Escalation and Expansion Part A: Area Under the Concentration Time Curve From Zero to 168 Hours (AUC0-168 h) of GEN3014	Venous blood samples were collected for analyzing concentrations of GEN3014. For the RRMM Dose Escalation 0.2/0.6 mg/kg arm, the participant underwent intraparticipant dose escalation in Cycle 1, where the participant received 0.2 mg/kg during the first week and 0.6 mg/kg from second week and beyond. Therefore, PK parameters were additionally calculated for Cycle 1 Day 8 dosing only in the RRMM Dose Escalation 0.2/0.6 mg/kg arm to account for the change in dosing over Cycle 1 in this arm.	Dose Escalation: Cycle 1 Day 1, Cycle 1 Day 8 (RRMM Dose Escalation: GEN3014 0.2/0.6 mg/kg only), Cycle 2 Day 1, Expansion Part A: Cycle 1 Day 1, Cycle 2 Day 1 (R/R DLBCL Expansion Part A: Cycle 1 Day 1 only) (cycle =28 days)
Dose Escalation and Expansion Part A: Number of Participants With Anti-Drug Antibodies (ADAs) to GEN3014	Venous blood samples were drawn for analysis of ADAs to GEN3014.	Dose Escalation: Baseline up to a max of approx. 34.5 months, Expansion Part A: Baseline up to a max of approx. 16.6 months
Dose Escalation: ORR	ORR was defined as the percentage of participants with a PR or better. The response in RRMM Cohorts was assessed following IMWG criteria 2016. Per IMWG criteria, PR was defined as ≥50% reduction of serum M-protein plus reduction in 24-h urinary M-protein by ≥90% or to <200 mg per 24 h. In addition to these criteria, if present at baseline, a ≥50% reduction in the size (SPD) of soft tissue plasmacytomas was also required.	Up to approximately 4 years 3 months
Dose Escalation and Expansion Part A: Clinical Benefit Rate (CBR)	CBR was defined as the percentage of participants with a best overall response of minimal response (MR), partial response (PR), very good partial response (VGPR), complete response (CR) or stringent complete response (sCR) as determined by the investigator per IMWG response criteria for RRMM participants. MR=≥25% but ≤49% reduction of serum M-protein, reduction of 24-h urine by 50%-89% and if present at baseline, ≥50% reduction in the size (SPD) of soft tissue plasmacytomas. PR=≥50% reduction of serum M-protein, reduction in 24-h urinary M-protein by ≥90% or to <200mg/24h and if present at baseline,≥50% reduction in SPD of soft tissue plasmacytomas. VGPR=Serum+urine M-protein detectable by IFE but not electrophoresis or ≥90% reduction in serum M-protein+urine M-protein level <100mg/24h. CR=Negative IFE on serum/urine + disappearance of soft tissue plasmacytomas and ≤5% plasma cells in bone marrow aspirates. sCR=CR+normal FLC ratio, absence of clonal cells in bone marrow biopsy by IHC.	Up to approximately 4 years 3 months
Dose Escalation, Expansion Part A and Expansion Part B: Duration of Response (DOR)	DOR was defined as time from first response (PR or better) to timing of disease progression or death (due to any cause), whichever came first.	Up to approximately 4 years 3 months
Dose Escalation, Expansion Part A and Expansion Part B: Time-to-response (TTR)	TTR was defined as the time from date of first dose, or date of randomization for participants in the Expansion Part B, to time of first response (PR or better).	Up to approximately 4 years 3 months
Dose Escalation, Expansion Part A and Expansion Part B: Progression-free Survival (PFS)	PFS was defined as the time from the date of first dose, or date of randomization for participants in the Expansion Part B, to the date of progression or death (due to any cause), whichever came first.	Up to approximately 4 years 3 months
Dose Escalation, Expansion Part A and Expansion Part B: Overall Survival (OS)	OS was defined as the time from the date of first dose, or date of randomization for participants in the Expansion Part B, to the date of death due to any cause.	Up to approximately 4 years 3 months
Expansion Part A and Part B: Number of Participants With AEs and SAEs	An AE was any untoward medical occurrence in a participant or clinical trial participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE was defined as an AE that met 1 of the following criteria: fatal or life-threatening, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect, was medically significant (jeopardized the participant or may have required medical or surgical intervention to prevent one of the outcomes listed above), required inpatient hospitalization or prolongation of existing hospitalization. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.	Up to approximately 4 years 3 months
Expansion Part B: Percentage of Participants With Very Good Partial Response (VGPR) or Better	Based on Investigator Assessment per IMWG 2016 Criteria, VGPR was defined as serum and urine M-protein detectable by immunofixation (IFE) but not on electrophoresis or ≥90% reduction in serum M-protein plus urine M-protein level <100 mg per 24 h. Data are reported for the percentage of participants with a VGPR or better.	Up to approximately 4 years 3 months
Expansion Part B: Percentage of Participants With Complete Response (CR) or Better	CR was defined as negative IFE on the serum and urine and disappearance of any soft tissue plasmacytomas and ≤5% plasma cells in bone marrow aspirates based on Investigator assessment per IMWG response criteria. Data are reported for the percentage of participants with CR or better.	Up to approximately 4 years 3 months
Expansion Part B: Time to Next Therapy (TTNT)	TTNT for participants in the Expansion Part B was defined as the time from randomization to the start of subsequent anti-cancer therapy. Participants who withdrew consent or were lost to follow up or died due to causes other than disease progression were censored at their last disease assessment.	Up to approximately 4 years 3 months
Expansion Part B: Number of Participants With Anti-GEN3014 Antibodies and Anti-Daratumumab Antibodies	Venous blood samples were drawn for analysis of ADAs to GEN3014 and daratumumab. In the GEN3014 arm, participants were tested for anti-GEN3014-antibodies; in the daratumumab arm, participants were tested for anti-daratumumab-antibodies.	Cycle 1 Day 22 up to a maximum of approximately 23.9 months (cycles = 28 days)

Collaborators and Investigators

• Sponsor: Genmab
• Investigators: Study Director: Study Official, Genmab

Publications and helpful links

Helpful Links

• Results Summary in Plain Language

Study record dates

Study Major Dates

• Study Start (Actual): March 9, 2021
• Primary Completion (Actual): June 30, 2025
• Study Completion (Actual): July 31, 2025

Study Registration Dates

• First Submitted: March 9, 2021
• First Submitted That Met QC Criteria: March 29, 2021
• First Posted (Actual): April 1, 2021

Study Record Updates

• Last Update Posted (Actual): May 19, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: monoclonal antibody; Hexabody®; Anti-CD38
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Neoplasms; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma; Leukemia, Myeloid; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Leukemia; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Recurrence; Leukemia, Myeloid, Acute; Lymphoma, Large B-Cell, Diffuse; Multiple Myeloma; Antineoplastic Agents; daratumumab
• Other Study ID Numbers: GCT3014-01; 2020-003781-40 (EudraCT Number); NL75422.056.21 (Registry Identifier: The Netherlands CCMO); 2023-507086-26-00 (Ctis: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No