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GEN3014 Safety Trial in Relapsed or Refractory Hematologic Malignancies

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ClinicalTrials.gov Identifier: NCT04824794
Recruitment Status : Recruiting
First Posted : April 1, 2021
Last Update Posted : April 1, 2021
Sponsor:
Information provided by (Responsible Party):
Genmab

Brief 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.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Biological: GEN3014 (HexaBody®-CD38) Phase 1 Phase 2

Detailed Description:
The purpose of the escalation part of the trial is to determine the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D), as well as to establish the safety profile of GEN3014 (HexaBody®-CD38) in Relapsed or Refractory Multiple Myeloma and Other Hematologic Malignancies

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 152 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Multicenter, Phase 1/2 Trial of GEN3014 (HexaBody®-CD38) in Relapsed or Refractory Multiple Myeloma and Other Hematologic Malignancies
Actual Study Start Date : March 22, 2021
Estimated Primary Completion Date : March 2023
Estimated Study Completion Date : November 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: Treatment
GEN3014
Biological: GEN3014 (HexaBody®-CD38)
GEN3014 is administered by intravenous (IV) infusion




Primary Outcome Measures :
  1. Escalation: Dose limiting toxicities (DLTs) [ Time Frame: DLTs will be assessed during the first cycle (21 days) in each cohort ]
    Incidence of DLTs

  2. Escalation: Adverse events [ Time Frame: AEs are collected throughout study until the end of the safety follow-up period (30 days after last dose). ]
    To assess the safety and tolerability of GEN3014 throughout the treatment period of patients participating in the trial


Secondary Outcome Measures :
  1. Escalation: To establish the pharmacokinetic profile (PK) profile of GEN3014 [ Time Frame: Assed throughout trial until the end of the safety follow-up period (30 days after last dose)] ]
    Maximum concentration of GEN3014 (Cmax) after dosing

  2. Escalation: To establish the PK profile of GEN3014 [ Time Frame: Assed throughout trial until the end of the safety follow-up period (30 days after last dose)] ]
    Time after dosing at which the maximum drug concentration was observed (Tmax)

  3. Escalation: To establish the PK profile of GEN3014 [ Time Frame: Assed throughout trial until the end of the safety follow-up period (30 days after last dose)] ]
    Time after dosing at which the lowest drug concentration is observed before the next dose is administered (C_Trough)

  4. Escalation: To establish the PK profile of GEN3014 [ Time Frame: Assed throughout trial until the end of the safety follow-up period (30 days after last dose)] ]
    Area-under-the-concentration-time curve from zero to last quantifiable sample(AUC_0-C last)

  5. Escalation: To establish the PK profile of GEN3014 [ Time Frame: Assed throughout trial until the end of the safety follow-up period (30 days after last dose)] ]
    Area-under-the-concentration-time curve from zero to 168 h (AUC_0-168 h)

  6. Escalation: To establish the PK profile of GEN3014 [ Time Frame: Assed throughout trial until the end of the safety follow-up period (30 days after last dose)] ]
    Accumulation ratios in Cmax (R_A, Cmax)

  7. Escalation: To establish the PK profile of GEN3014 [ Time Frame: Assed throughout trial until the end of the safety follow-up period (30 days after last dose)] ]
    Accumulation ratios in area-under-the-concentration-time curve (R_A, AUC)

  8. Escalation: Evaluate immunogenicity of GEN3014 [ Time Frame: ADA are collected throughout trial until the end of the safety follow-up period (30 days after last dose) ]
    Anti-drug antibody response (ADA)



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04824794


Contacts
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Contact: Genmab A/S Trial Information +45 70202728 clinicaltrials@genmab.com

Locations
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United States, New Jersey
Hackensack University Medical Center Not yet recruiting
Hackensack, New Jersey, United States, 07601-1914
United States, North Carolina
Levine Cancer Institute Not yet recruiting
Charlotte, North Carolina, United States, 28204
United States, Wisconsin
Medical college of Wisconsin Not yet recruiting
Milwaukee, Wisconsin, United States, 53226
Denmark
Aalborg Universitet Not yet recruiting
Aalborg, Denmark
Vejle Hospital Recruiting
Vejle, Denmark
Spain
University of Navarra Not yet recruiting
Pamplona, Spain
University Hospital of Salamanca Not yet recruiting
Salamanca, Spain
Sweden
Karolinska Institute Not yet recruiting
Huddinge, Sweden
Universitetssjukhuset i Lund Not yet recruiting
Lund, Sweden
Sponsors and Collaborators
Genmab
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Responsible Party: Genmab
ClinicalTrials.gov Identifier: NCT04824794    
Other Study ID Numbers: GCT3014-01
First Posted: April 1, 2021    Key Record Dates
Last Update Posted: April 1, 2021
Last Verified: March 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Hematologic Neoplasms
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Neoplasms by Site