search
Back to results

GEN3014 Safety Trial in Relapsed or Refractory Hematologic Malignancies

Primary Purpose

Multiple Myeloma (MM), Diffuse Large B Cell Lymphoma (DLBCL), Acute Myeloid Leukemia (AML)

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
GEN3014
Daratumumab
Sponsored by
Genmab
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma (MM) focused on measuring Hexabody®, Anti-CD38, monoclonal antibody

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria (Escalation)

  1. Must be at least 18 years of age.
  2. Must sign an informed consent form (ICF) prior to any Screening procedures.
  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.
  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 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.

    Specific 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

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

  11. For anti-CD38 mAb-naive RRMM Cohort: 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 RRMM subjects will be recruited from countries where anti-CD38 therapies are not available.
  12. For anti-CD38 mAb-treated RRMM Cohort: 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); or corrected serum calcium ≤14.0 mg/dL (≤3.5 mmol/L).

Exclusion Criteria

  1. Prior treatment with an anti-CD38 antibody except daratumumab or isatuximab.
  2. Treatment with an anti-cancer agent, 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.
  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
  9. Known medical history or ongoing hepatitis C infection that has not been cured.
  10. HIV positive at screening
  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.

Sites / Locations

  • Winship Cancer Institute
  • John Theurer Cancer Center
  • Levine Cancer Institute
  • University Hospitals Cleveland Medical CenterRecruiting
  • Medical college of WisconsinRecruiting
  • The Alfred HospitalRecruiting
  • Royal Prince Alfred HospitalRecruiting
  • Fakultni Nemocnice Brno
  • Vseobecna fakultni nemocnice
  • Fakultni Nemocnice Hradec Kralove FNHKRecruiting
  • Fakultni Nemocnice Olomouc (FNOL)
  • FNO - Fakultni nemocnice Ostrava
  • Aalborg UniversitetRecruiting
  • Vejle HospitalRecruiting
  • CHRU de Lille
  • CHRU de Nantes
  • ARENSIA Exploratory Medicine LLCRecruiting
  • National & Kapodistrian University of Athens
  • University of Athens NKUA
  • University General Hospital of Patras
  • Ahepa University General hospital
  • Dél-Pesti Centrumkórház Országos Hematológiai és Infektológiai Intézet
  • Semmelweis Egyetem Belgyógyászati és Hematológiai Klinika
  • SzSzB Megyei Egyetemi Oktatokorhaz Josa Andras Oktatokorhaz
  • Chonnam National University Hwasun HospitalRecruiting
  • Pusan National University Hospital PNUHRecruiting
  • Gachon University Gil Medical Center
  • Samsung Medical CenterRecruiting
  • Seoul National University Hospital
  • Institute of Oncology, ARENSIA Exploratory MedicineRecruiting
  • Maastricht UMC
  • Erasmus MCRecruiting
  • UMC Utrecht
  • University Centrum KliniczneRecruiting
  • Pratia Onkologia KatowiceRecruiting
  • Pratia MCMRecruiting
  • Wroclaw Medical University
  • University of NavarraRecruiting
  • University Hospital of SalamancaRecruiting
  • Karolinska InstituteRecruiting
  • Universitetssjukhuset i LundRecruiting
  • Arensia Exploratory MedicineRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

GEN3014

Daratumumab

Arm Description

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)

Participants in Expansion Part B with - RRMM (anti-CD38 mAb-naïve)

Outcomes

Primary Outcome Measures

Dose Escalation: Number of Participants with Dose Limiting Toxicities (DLTs)
To determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) to be studied in the Expansion part. DLT will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) criteria version 5.0.
Dose Escalation: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Expansion Part A: Objective Response Rate (ORR) of GEN3014
ORR is defined as the percentage of participants with a partial response (PR), or better based on International Myeloma Working Group (IMWG) criteria for MM participants, based on Lugano criteria for DLBCL participants, and based on International Working Group (IWG) response criteria for AML participants.
Expansion Part B: Objective Response Rate (ORR) of GEN3014 IV vs Daratumumab SC in Anti-CD38 mAb-naive RRMM Participants
ORR is defined as the percentage of participants with a PR, or better based on IMWG criteria.

Secondary Outcome Measures

Dose Escalation: Maximum (peak) Plasma Concentration (Cmax) of GEN3014
Dose Escalation: Time to Reach Cmax (Tmax) of GEN3014
Dose Escalation: Pre-dose (trough) Concentrations (Cthrough) of GEN3014
Dose Escalation: Area Under the Concentration Time Curve From Zero to Last Quantifiable Sample (AUC0-last)
Dose Escalation: Area Under the Concentration Time Curve From Zero to 168 hours (AUC0-168 h)
Dose Escalation: Accumulation Ratio in Cmax (RA, Cmax)
Dose Escalation: Accumulation Ratio in AUC (RA, AUC)
Dose Escalation: Number of NK-cells and Other Leukocytes Subsets
NK-cells and other leukocytes absolute counts in blood and tumor samples will be assessed.
Dose Escalation: Percentage of NK-cells and Other Leukocytes Subsets
NK-cells and other leukocytes percentage in blood and tumor samples will be assessed.
Dose Escalation: Change From Baseline in Cytokine levels up to Cycle 1
Change in cytokine levels in blood samples will be assessed.
Dose Escalation: Change From Baseline in CH50 and C2 level up to Cycle 1
Change in CH50 and C2 levels in blood samples will be assessed.
Dose Escalation: Number of Participants with Anti-Drug Antibody (ADA) of GEN3014
Dose Escalation: Objective Response Rate (ORR) of GEN3014
ORR is defined as the percentage of participants with a PR or better based on IMWG criteria for MM participants, and based on IWG response criteria for AML participants.
Dose Escalation: Clinical Benefit Rate (CBR) of GEN3014
CBR was determined by the investigator according to the IMWG response criteria for MM participants.
Dose Escalation: Duration of Response (DOR) of GEN3014
DOR is defined as time from first response (PR or better) to timing of disease progression or death (due to any cause), whichever comes first based on IMWG criteria for MM participants and based on IWG response criteria for AML participants.
Dose Escalation: Time-to-response (TTR) of GEN3014
TTR is defined as the time from date of first dose to time of response (PR or better) based on IMWG criteria for MM participants and based on IWG response criteria for AML participants.
Dose Escalation: Progression-free survival (PFS) of GEN3014
PFS is defined as the time from the date of the first dose, or date of randomization to the date of progression or death (due to any cause), whichever comes first based on IMWG criteria for MM participants and based on IWG response criteria for AML participants.
Dose Escalation: Overall Survival (OS) of GEN3014
OS is defined as the time from the date of first dose to the date of death due to any cause.
Expansion Part A: Clinical Benefit Rate (CBR) of GEN3014
CBR was determined by the investigator according to the IMWG response criteria for MM participants.
Expansion Part A: Duration of Response (DOR) of GEN3014
DOR is defined as time from first response (PR or better) to timing of disease progression or death (due to any cause), whichever comes first based on IMWG criteria for MM participants, based on Lugano criteria for DLBCL participants, and based on IWG response criteria for AML participants.
Expansion Part A: Time-to-response (TTR) of GEN3014
TTR is defined as the time from date of first dose to time of response (PR or better) for MM participants, based on Lugano criteria for DLBCL participants, and based on IWG response criteria for AML participants.
Expansion Part A: Progression-free survival (PFS) of GEN3014
PFS is defined as the time from the date of the first dose to the date of progression or death (due to any cause), whichever comes first based on IMWG criteria for MM participants, based on Lugano criteria for DLBCL participants, and based on IWG response criteria for AML participants.
Expansion Part A: Overall Survival (OS) of GEN3014
OS is defined as the time from the date of first dose to the date of death due to any cause.
Expansion Part A: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) per CTCAE v5.0
Expansion Part A: Number of Participants with Anti-Drug Antibody (ADA) of GEN3014
Expansion Part A: Maximum (peak) Plasma Concentration (Cmax) of GEN3014
Expansion Part A: Time to Reach Cmax (Tmax) of GEN3014
Expansion Part A: Pre-dose (trough) Concentrations (Cthrough) of GEN3014
Expansion Part A: Area Under the Concentration Time Curve From Zero to Last Quantifiable Sample (AUC0-last)
Expansion Part A: Area Under the Concentration Time Curve From Zero to 168 hours (AUC0-168 h)
Expansion Part A: Accumulation Ratio in Cmax (RA, Cmax)
Expansion Part A: Accumulation Ratio in AUC (RA, AUC)
Expansion Part A: Accumulation Ratio in Cthrough (RA,Cthrough)
Expansion Part A: Number of NK-cells and Other Leukocytes Subsets
NK-cells and other leukocytes absolute counts in blood and tumor samples will be assessed.
Expansion Part A: Percentage of NK-cells and Other Leukocytes Subsets
NK-cells and other leukocytes percentage in blood and tumor samples will be assessed.
Expansion Part A: Change From Baseline in Cytokine levels up to Cycle 1
Change in cytokine levels in blood samples will be assessed.
Expansion Part A: Change From Baseline in CH50 and C2 level up to Cycle 1
Change in CH50 and C2 levels in blood samples will be assessed.
Expansion Part B: Ctrough levels of GEN3014 IV or Daratumumab SC on Cycle 3 Day 1
Expansion Part B: Very Good Partial Response (VGPR), or better of GEN3014 IV vs Daratumumab SC
Expansion Part B: Complete Response (CR) or better of GEN3014 IV vs Daratumumab SC
Expansion Part B: Duration of Response (DOR) of GEN3014 IV vs Daratumumab SC
DOR is defined as time from first response (PR or better) to timing of disease progression or death (due to any cause), whichever comes first based on IMWG criteria for MM participants.
Expansion Part B: Time-to-response (TTR) of GEN3014 IV vs Daratumumab SC
TTR is defined as the time from date of randomization, to time of response (PR or better) based on IMWG criteria for MM participants.
Expansion Part B: Progression-free Survival (PFS) of GEN3014 IV vs Daratumumab SC
PFS is defined as the time from date of randomization to the date of progression or death (due to any cause), whichever comes first based on IMWG criteria for MM participants.
Expansion Part B: Overall Survival (OS) of GEN3014 IV vs Daratumumab SC
OS is defined as the time from date of randomization to the date of death due to any cause.
Expansion Part B: Time to Next Therapy (TTNT)
Time to next therapy (TTNT) for participants in the Expansion Part B is defined as the time from date of randomization to the start of subsequent anti-cancer therapy.
Expansion Part B: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) per CTCAE v5.0
Expansion Part B: Number of Participants with Anti-Drug Antibody (ADA) of GEN3014, Anti-daratumumab antibodies and Anti- rHuPH20

Full Information

First Posted
March 9, 2021
Last Updated
October 4, 2023
Sponsor
Genmab
search

1. Study Identification

Unique Protocol Identification Number
NCT04824794
Brief Title
GEN3014 Safety Trial in Relapsed or Refractory Hematologic Malignancies
Official Title
An Open-Label, Multicenter, Phase 1/2 Trial of GEN3014 (HexaBody®-CD38) in Relapsed or Refractory Multiple Myeloma and Other Hematologic Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 9, 2021 (Actual)
Primary Completion Date
October 2024 (Anticipated)
Study Completion Date
February 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genmab

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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: The Dose Escalation will test increasing doses of GEN3014 to find a safe dose level to be tested in the other two parts. Expansion Part A will further test the GEN3014 dose determined from the Dose Escalation Part. Expansion Part B will compare intravenous (IV) GEN3014 with the approved multiple myeloma drug, subcutaneous (SC) daratumumab. Participants in the US will not participate Expansion Part B. Participants will receive either investigational 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.
Detailed Description
This trial will be conducted in 3 parts: Dose Escalation (phase 1), Expansion Parts, A and B (phase 2). All participants in the Dose Escalation, GEN3014 will be evaluated in RRMM and R/R AML, 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. Expansion Part A, GEN3014 will be further evaluated in 4 cohorts: anti-CD38 mAb-naive RRMM, anti-CD38 mAb-refractory RRMM, R/R DLBCL, and R/R AML at the RP2D identified from the Dose Escalation per protocol. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma (MM), Diffuse Large B Cell Lymphoma (DLBCL), Acute Myeloid Leukemia (AML)
Keywords
Hexabody®, Anti-CD38, monoclonal antibody

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Model Description
Dose escalation part is sequential while the expansion Part A cohorts are parallel. Expansion Part B is sequential to Expansion Part A RRMM cohort. In Expansion Part B, participants with RRMM are randomized (1:1) to treatment.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
252 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
GEN3014
Arm Type
Experimental
Arm Description
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)
Arm Title
Daratumumab
Arm Type
Active Comparator
Arm Description
Participants in Expansion Part B with - RRMM (anti-CD38 mAb-naïve)
Intervention Type
Biological
Intervention Name(s)
GEN3014
Other Intervention Name(s)
HexaBody®-CD38
Intervention Description
GEN3014 is administered by intravenous (IV) infusion.
Intervention Type
Drug
Intervention Name(s)
Daratumumab
Other Intervention Name(s)
DARZALEX FASPRO®
Intervention Description
Daratumumab is administered by subcutaneous (SC) injections.
Primary Outcome Measure Information:
Title
Dose Escalation: Number of Participants with Dose Limiting Toxicities (DLTs)
Description
To determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) to be studied in the Expansion part. DLT will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) criteria version 5.0.
Time Frame
Up to 28 days during the first cycle
Title
Dose Escalation: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame
From first dose until the end of the safety follow-up period (30 days after last dose)
Title
Expansion Part A: Objective Response Rate (ORR) of GEN3014
Description
ORR is defined as the percentage of participants with a partial response (PR), or better based on International Myeloma Working Group (IMWG) criteria for MM participants, based on Lugano criteria for DLBCL participants, and based on International Working Group (IWG) response criteria for AML participants.
Time Frame
Up to 8 years
Title
Expansion Part B: Objective Response Rate (ORR) of GEN3014 IV vs Daratumumab SC in Anti-CD38 mAb-naive RRMM Participants
Description
ORR is defined as the percentage of participants with a PR, or better based on IMWG criteria.
Time Frame
Up to 8 years
Secondary Outcome Measure Information:
Title
Dose Escalation: Maximum (peak) Plasma Concentration (Cmax) of GEN3014
Time Frame
Predose and postdose at multiple timepoints of each Cycle (Cycle length=28 days)
Title
Dose Escalation: Time to Reach Cmax (Tmax) of GEN3014
Time Frame
Predose and postdose at multiple timepoints of each Cycle (Cycle length=28 days)
Title
Dose Escalation: Pre-dose (trough) Concentrations (Cthrough) of GEN3014
Time Frame
Predose and postdose at multiple timepoints of each Cycle (Cycle length=28 days)
Title
Dose Escalation: Area Under the Concentration Time Curve From Zero to Last Quantifiable Sample (AUC0-last)
Time Frame
Predose and postdose at multiple timepoints of each Cycle (Cycle length=28 days)
Title
Dose Escalation: Area Under the Concentration Time Curve From Zero to 168 hours (AUC0-168 h)
Time Frame
Predose and postdose at multiple timepoints of each Cycle (Cycle length=28 days)
Title
Dose Escalation: Accumulation Ratio in Cmax (RA, Cmax)
Time Frame
Predose and postdose at multiple timepoints of each Cycle (Cycle length=28 days)
Title
Dose Escalation: Accumulation Ratio in AUC (RA, AUC)
Time Frame
Predose and postdose at multiple timepoints of each Cycle (Cycle length=28 days)
Title
Dose Escalation: Number of NK-cells and Other Leukocytes Subsets
Description
NK-cells and other leukocytes absolute counts in blood and tumor samples will be assessed.
Time Frame
Predose and postdose at multiple timepoints of each Cycle up to Cycle 6 and thereafter only in even Cycles (Cycle length=28 days)
Title
Dose Escalation: Percentage of NK-cells and Other Leukocytes Subsets
Description
NK-cells and other leukocytes percentage in blood and tumor samples will be assessed.
Time Frame
Predose and postdose at multiple timepoints of each Cycle up to Cycle 6 and thereafter only in even Cycles (Cycle length=28 days)
Title
Dose Escalation: Change From Baseline in Cytokine levels up to Cycle 1
Description
Change in cytokine levels in blood samples will be assessed.
Time Frame
Cycle 1 (cycle length = 28 days)
Title
Dose Escalation: Change From Baseline in CH50 and C2 level up to Cycle 1
Description
Change in CH50 and C2 levels in blood samples will be assessed.
Time Frame
Cycle 1 (cycle length = 28 days)
Title
Dose Escalation: Number of Participants with Anti-Drug Antibody (ADA) of GEN3014
Time Frame
From first dose until treatment discontinuation (Up to 8 years)
Title
Dose Escalation: Objective Response Rate (ORR) of GEN3014
Description
ORR is defined as the percentage of participants with a PR or better based on IMWG criteria for MM participants, and based on IWG response criteria for AML participants.
Time Frame
Up to 8 years
Title
Dose Escalation: Clinical Benefit Rate (CBR) of GEN3014
Description
CBR was determined by the investigator according to the IMWG response criteria for MM participants.
Time Frame
Up to 8 years
Title
Dose Escalation: Duration of Response (DOR) of GEN3014
Description
DOR is defined as time from first response (PR or better) to timing of disease progression or death (due to any cause), whichever comes first based on IMWG criteria for MM participants and based on IWG response criteria for AML participants.
Time Frame
Up to 8 years
Title
Dose Escalation: Time-to-response (TTR) of GEN3014
Description
TTR is defined as the time from date of first dose to time of response (PR or better) based on IMWG criteria for MM participants and based on IWG response criteria for AML participants.
Time Frame
Up to 8 years
Title
Dose Escalation: Progression-free survival (PFS) of GEN3014
Description
PFS is defined as the time from the date of the first dose, or date of randomization to the date of progression or death (due to any cause), whichever comes first based on IMWG criteria for MM participants and based on IWG response criteria for AML participants.
Time Frame
Up to 8 years
Title
Dose Escalation: Overall Survival (OS) of GEN3014
Description
OS is defined as the time from the date of first dose to the date of death due to any cause.
Time Frame
Up to 8 years
Title
Expansion Part A: Clinical Benefit Rate (CBR) of GEN3014
Description
CBR was determined by the investigator according to the IMWG response criteria for MM participants.
Time Frame
Up to 8 years
Title
Expansion Part A: Duration of Response (DOR) of GEN3014
Description
DOR is defined as time from first response (PR or better) to timing of disease progression or death (due to any cause), whichever comes first based on IMWG criteria for MM participants, based on Lugano criteria for DLBCL participants, and based on IWG response criteria for AML participants.
Time Frame
Up to 8 years
Title
Expansion Part A: Time-to-response (TTR) of GEN3014
Description
TTR is defined as the time from date of first dose to time of response (PR or better) for MM participants, based on Lugano criteria for DLBCL participants, and based on IWG response criteria for AML participants.
Time Frame
Up to 8 years
Title
Expansion Part A: Progression-free survival (PFS) of GEN3014
Description
PFS is defined as the time from the date of the first dose to the date of progression or death (due to any cause), whichever comes first based on IMWG criteria for MM participants, based on Lugano criteria for DLBCL participants, and based on IWG response criteria for AML participants.
Time Frame
Up to 8 years
Title
Expansion Part A: Overall Survival (OS) of GEN3014
Description
OS is defined as the time from the date of first dose to the date of death due to any cause.
Time Frame
Up to 8 years
Title
Expansion Part A: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) per CTCAE v5.0
Time Frame
From first dose until the end of the safety follow-up period (30 days after last dose)
Title
Expansion Part A: Number of Participants with Anti-Drug Antibody (ADA) of GEN3014
Time Frame
From first dose until treatment discontinuation (Up to 8 years)
Title
Expansion Part A: Maximum (peak) Plasma Concentration (Cmax) of GEN3014
Time Frame
Predose and postdose at multiple timepoints of each Cycle (Cycle length=28 days)
Title
Expansion Part A: Time to Reach Cmax (Tmax) of GEN3014
Time Frame
Predose and postdose at multiple timepoints of each Cycle (Cycle length=28 days)
Title
Expansion Part A: Pre-dose (trough) Concentrations (Cthrough) of GEN3014
Time Frame
Predose and postdose at multiple timepoints of each Cycle (Cycle length=28 days)
Title
Expansion Part A: Area Under the Concentration Time Curve From Zero to Last Quantifiable Sample (AUC0-last)
Time Frame
Predose and postdose at multiple timepoints of each Cycle (Cycle length=28 days)
Title
Expansion Part A: Area Under the Concentration Time Curve From Zero to 168 hours (AUC0-168 h)
Time Frame
Predose and postdose at multiple timepoints of each Cycle (Cycle length=28 days)
Title
Expansion Part A: Accumulation Ratio in Cmax (RA, Cmax)
Time Frame
Predose and postdose at multiple timepoints of each Cycle (Cycle length=28 days)
Title
Expansion Part A: Accumulation Ratio in AUC (RA, AUC)
Time Frame
Predose and postdose at multiple timepoints of each Cycle (Cycle length=28 days)
Title
Expansion Part A: Accumulation Ratio in Cthrough (RA,Cthrough)
Time Frame
Predose and postdose at multiple timepoints of each Cycle (Cycle length=28 days)
Title
Expansion Part A: Number of NK-cells and Other Leukocytes Subsets
Description
NK-cells and other leukocytes absolute counts in blood and tumor samples will be assessed.
Time Frame
Predose and postdose at multiple timepoints of each Cycle up to Cycle 6 and thereafter only in even Cycles (Cycle length=28 days)
Title
Expansion Part A: Percentage of NK-cells and Other Leukocytes Subsets
Description
NK-cells and other leukocytes percentage in blood and tumor samples will be assessed.
Time Frame
Predose and postdose at multiple timepoints of each Cycle up to Cycle 6 and thereafter only in even Cycles (Cycle length=28 days)
Title
Expansion Part A: Change From Baseline in Cytokine levels up to Cycle 1
Description
Change in cytokine levels in blood samples will be assessed.
Time Frame
Cycle 1 (cycle length = 28 days)
Title
Expansion Part A: Change From Baseline in CH50 and C2 level up to Cycle 1
Description
Change in CH50 and C2 levels in blood samples will be assessed.
Time Frame
Cycle 1 (cycle length = 28 days)
Title
Expansion Part B: Ctrough levels of GEN3014 IV or Daratumumab SC on Cycle 3 Day 1
Time Frame
Predose and postdose at multiple timepoints of each Cycle (Cycle length=28 days)
Title
Expansion Part B: Very Good Partial Response (VGPR), or better of GEN3014 IV vs Daratumumab SC
Time Frame
Up to 8 years
Title
Expansion Part B: Complete Response (CR) or better of GEN3014 IV vs Daratumumab SC
Time Frame
Up to 8 years
Title
Expansion Part B: Duration of Response (DOR) of GEN3014 IV vs Daratumumab SC
Description
DOR is defined as time from first response (PR or better) to timing of disease progression or death (due to any cause), whichever comes first based on IMWG criteria for MM participants.
Time Frame
Up to 8 years
Title
Expansion Part B: Time-to-response (TTR) of GEN3014 IV vs Daratumumab SC
Description
TTR is defined as the time from date of randomization, to time of response (PR or better) based on IMWG criteria for MM participants.
Time Frame
Up to 8 years
Title
Expansion Part B: Progression-free Survival (PFS) of GEN3014 IV vs Daratumumab SC
Description
PFS is defined as the time from date of randomization to the date of progression or death (due to any cause), whichever comes first based on IMWG criteria for MM participants.
Time Frame
Up to 8 years
Title
Expansion Part B: Overall Survival (OS) of GEN3014 IV vs Daratumumab SC
Description
OS is defined as the time from date of randomization to the date of death due to any cause.
Time Frame
Up to 8 years
Title
Expansion Part B: Time to Next Therapy (TTNT)
Description
Time to next therapy (TTNT) for participants in the Expansion Part B is defined as the time from date of randomization to the start of subsequent anti-cancer therapy.
Time Frame
Up to 8 years
Title
Expansion Part B: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) per CTCAE v5.0
Time Frame
From first dose until the end of the safety follow-up period (30 days after last dose)
Title
Expansion Part B: Number of Participants with Anti-Drug Antibody (ADA) of GEN3014, Anti-daratumumab antibodies and Anti- rHuPH20
Time Frame
From first dose until treatment discontinuation (Up to 8 years)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria Must have fresh bone marrow samples collected at Screening. 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. Expansion part A - 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 PI and an 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 subjects 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. 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 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 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. 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Genmab Trial Information
Phone
+45 70202728
Email
clinicaltrials@genmab.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Official
Organizational Affiliation
Genmab
Official's Role
Study Director
Facility Information:
Facility Name
Winship Cancer Institute
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
John Theurer Cancer Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
Levine Cancer Institute
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28150
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
University Hospitals Cleveland Medical Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Individual Site Status
Recruiting
Facility Name
Medical college of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Individual Site Status
Recruiting
Facility Name
The Alfred Hospital
City
Melbourne
Country
Australia
Individual Site Status
Recruiting
Facility Name
Royal Prince Alfred Hospital
City
Sydney
Country
Australia
Individual Site Status
Recruiting
Facility Name
Fakultni Nemocnice Brno
City
Brno
Country
Czechia
Individual Site Status
Active, not recruiting
Facility Name
Vseobecna fakultni nemocnice
City
Nové Město
Country
Czechia
Individual Site Status
Active, not recruiting
Facility Name
Fakultni Nemocnice Hradec Kralove FNHK
City
Nový Hradec Králové
Country
Czechia
Individual Site Status
Recruiting
Facility Name
Fakultni Nemocnice Olomouc (FNOL)
City
Olomouc
Country
Czechia
Individual Site Status
Active, not recruiting
Facility Name
FNO - Fakultni nemocnice Ostrava
City
Poruba
Country
Czechia
Individual Site Status
Active, not recruiting
Facility Name
Aalborg Universitet
City
Aalborg
Country
Denmark
Individual Site Status
Recruiting
Facility Name
Vejle Hospital
City
Vejle
Country
Denmark
Individual Site Status
Recruiting
Facility Name
CHRU de Lille
City
Lille
Country
France
Individual Site Status
Active, not recruiting
Facility Name
CHRU de Nantes
City
Nantes
Country
France
Individual Site Status
Active, not recruiting
Facility Name
ARENSIA Exploratory Medicine LLC
City
Tbilisi
Country
Georgia
Individual Site Status
Recruiting
Facility Name
National & Kapodistrian University of Athens
City
Athens
Country
Greece
Individual Site Status
Active, not recruiting
Facility Name
University of Athens NKUA
City
Athens
Country
Greece
Individual Site Status
Active, not recruiting
Facility Name
University General Hospital of Patras
City
Río
Country
Greece
Individual Site Status
Active, not recruiting
Facility Name
Ahepa University General hospital
City
Thessaloníki
Country
Greece
Individual Site Status
Active, not recruiting
Facility Name
Dél-Pesti Centrumkórház Országos Hematológiai és Infektológiai Intézet
City
Budapest
Country
Hungary
Individual Site Status
Not yet recruiting
Facility Name
Semmelweis Egyetem Belgyógyászati és Hematológiai Klinika
City
Budapest
Country
Hungary
Individual Site Status
Not yet recruiting
Facility Name
SzSzB Megyei Egyetemi Oktatokorhaz Josa Andras Oktatokorhaz
City
Nyíregyháza
Country
Hungary
Individual Site Status
Not yet recruiting
Facility Name
Chonnam National University Hwasun Hospital
City
Gwangju
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Pusan National University Hospital PNUH
City
Pusan
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Gachon University Gil Medical Center
City
Seongnam
Country
Korea, Republic of
Individual Site Status
Active, not recruiting
Facility Name
Samsung Medical Center
City
Seoul
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Seoul National University Hospital
City
Seoul
Country
Korea, Republic of
Individual Site Status
Not yet recruiting
Facility Name
Institute of Oncology, ARENSIA Exploratory Medicine
City
Chisinau
Country
Moldova, Republic of
Individual Site Status
Recruiting
Facility Name
Maastricht UMC
City
Maastricht
Country
Netherlands
Individual Site Status
Active, not recruiting
Facility Name
Erasmus MC
City
Rotterdam
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
UMC Utrecht
City
Utrecht
Country
Netherlands
Individual Site Status
Active, not recruiting
Facility Name
University Centrum Kliniczne
City
Gdańsk
Country
Poland
Individual Site Status
Recruiting
Facility Name
Pratia Onkologia Katowice
City
Katowice
Country
Poland
Individual Site Status
Recruiting
Facility Name
Pratia MCM
City
Kraków
Country
Poland
Individual Site Status
Recruiting
Facility Name
Wroclaw Medical University
City
Wrocław
Country
Poland
Individual Site Status
Not yet recruiting
Facility Name
University of Navarra
City
Pamplona
Country
Spain
Individual Site Status
Recruiting
Facility Name
University Hospital of Salamanca
City
Salamanca
Country
Spain
Individual Site Status
Recruiting
Facility Name
Karolinska Institute
City
Huddinge
Country
Sweden
Individual Site Status
Recruiting
Facility Name
Universitetssjukhuset i Lund
City
Lund
Country
Sweden
Individual Site Status
Recruiting
Facility Name
Arensia Exploratory Medicine
City
Kyiv
Country
Ukraine
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

GEN3014 Safety Trial in Relapsed or Refractory Hematologic Malignancies

We'll reach out to this number within 24 hrs