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First-in-Human (FIH) Trial of GEN3009 in Subjects With Relapsed or Refractory B-Cell Non-Hodgkin Lymphomas

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ClinicalTrials.gov Identifier: NCT04358458
Recruitment Status : Recruiting
First Posted : April 24, 2020
Last Update Posted : August 26, 2020
Sponsor:
Information provided by (Responsible Party):
Genmab

Tracking Information
First Submitted Date  ICMJE April 1, 2020
First Posted Date  ICMJE April 24, 2020
Last Update Posted Date August 26, 2020
Actual Study Start Date  ICMJE March 24, 2020
Estimated Primary Completion Date November 30, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 20, 2020)
  • Maximum Tolerated Dose [ Time Frame: DLTs are assessed during the first treatment cycle (28 days) in each cohort. ]
    Dose liming toxicity (DLT) will be monitored to determine the maximum tolerated dose (MTD) and/or the Recommended Phase 2 Dose (RP2D) of GEN3009.
  • Adverse events [ Time Frame: AEs are collected throughout study until the end of the safety follow-up period (30 days after last dose). ]
    Incidence of treatment-emergent adverse events (AEs) as assessed by National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), version 5.0
  • Safety laboratory parameters (hematology) [ Time Frame: Safety laboratory data are collected at baseline, during all study cycles until the end of the safety follow-up period (30 days after last dose). ]
    CTCAE Grade changes from Baseline of hematology parameters: Hemoglobin, hematocrit, white blood cells including differential, neutrophils, basophils, eosinophils, absolute and percentage of lymphocytes, monocytes, reticulocytes, platelets, proportion of prolymphocytes.
  • Safety laboratory parameters (biochemistry) [ Time Frame: Safety laboratory data are collected at baseline, during all study cycles until the end of the safety follow-up period (30 days after last dose). ]
    CTCAE Grade changes from Baseline of biochemistry parameters: albumin, alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), bicarbonate, lactate dehydrogenase (LDH), calcium, chloride, magnesium, inorganic phosphorus (phosphate), sodium, potassium, creatinine, total bilirubin, blood urea nitrogen (BUN) or urea, uric acid, glucose, total protein, C reactive protein, D-dimer, ferritin.
  • Safety laboratory parameters (coagulation) [ Time Frame: Safety laboratory data are collected at baseline, during all study cycles until the end of the safety follow-up period (30 days after last dose). ]
    CTCAE Grade changes from Baseline of coagulation parameters: International normalized ratio (INR), activated partial thromboplastin time (aPTT), and fibrinogen.
  • Safety laboratory parameters (Immunoglobulins) [ Time Frame: Safety laboratory data are collected at baseline, during each treatment cycle, and at time of treatment discontinuation ]
    CTCAE Grade changes from Baseline of Immunoglobulins IgA, IgG, IgM
  • Safety laboratory parameters (urinalysis) [ Time Frame: Safety laboratory data are collected at baseline, during each treatment cycle, and at time of treatment discontinuation ]
    CTCAE Grade changes from baseline of urinalysis parameters: pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase, specific gravity, urine pregnancy testing as applicable.
  • Vital signs (body temperature) [ Time Frame: Vital signs are collected throughout study until the end of the safety follow-up period (30 days after last dose). ]
    Changes in body temperature will be measured by degrees Celsius (°C)
  • Vital signs (blood pressure) [ Time Frame: Vital signs are collected throughout study until the end of the safety follow-up period (30 days after last dose). ]
    Changes in systolic and diastolic blood pressure will be measured by millimetres of mercury (mmHg)
  • Vital signs (heart rate) [ Time Frame: Vital signs are collected throughout study until the end of the safety follow-up period (30 days after last dose). ]
    Changes in heart rate will be measured by beats per minute.
  • Vital signs (oxygen saturation) [ Time Frame: Vital signs are collected throughout study until the end of the safety follow-up period (30 days after last dose). ]
    Changes in oxygen saturation will be measured by peripheral oxygen saturation (SpO2)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE First-in-Human (FIH) Trial of GEN3009 in Subjects With Relapsed or Refractory B-Cell Non-Hodgkin Lymphomas
Official Title  ICMJE Safety and Efficacy of GEN3009 (DuoHexaBody®-CD37) in Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma - A First-in-Human, Open-label, Phase 1/2a Dose Escalation Trial With Dose Expansion Cohorts
Brief Summary The aim of this first-in-human trial is to characterize the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic characteristics of GEN3009 (DuoHexabody®-CD37) in subjects with relapsed/refractory B-cell Non-Hodgkin Lymphoma (NHL).
Detailed Description

This trial is a first-in-human (FIH), open-label, multicenter trial to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary efficacy of GEN3009 in subjects with relapsed/refractory B-cell NHL (both aggressive and indolent subtypes).

The trial will be conducted in 2 parts; Dose Escalation and Dose Expansion. In the Dose Escalation part, GEN3009 will be administered by intravenous (IV) infusions at various dose levels in 28-day cycles. Dose Limiting Toxicity (DLT) will be assessed during the first treatment cycle and the Maximum Tolerated Dose (MTD) will be identified. Additional subjects will be treated in the Dose Expansion at the Recommended Phase 2 Dose (RP2D).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE B-cell Non-Hodgkin Lymphoma
Intervention  ICMJE Drug: GEN3009
GEN3009 will be administered by intravenous (IV) infusions at various dose levels in 28-day cycles. Expansion cohorts will be treated at the Recommended Phase 2 Dose (RP2D).
Other Name: DuoHexaBody®-CD37
Study Arms  ICMJE Experimental: Treatment Administered
Intervention: Drug: GEN3009
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 20, 2020)
120
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 30, 2023
Estimated Primary Completion Date November 30, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Be at least 18 years of age.
  2. Must sign an informed consent form prior to any screening procedures.
  3. Has histologically or cytologically confirmed relapsed and/or refractory B-cell NHL with no available standard therapy or is not a candidate for available standard therapy, and for whom, in the opinion of the investigator, experimental therapy with GEN3009 may be beneficial. All subjects must have received at least two prior lines of systemic therapy.
  4. Has one of the specified subtypes for B-cell NHL for the Dose Escalation and Dose Expansion parts of the study.
  5. Has measurable disease for B-cell NHL or has active disease for Chronic Lymphocytic Leukemia (CLL).
  6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
  7. Has adequate hepatic, renal, and bone marrow functions.
  8. Before the first dose of GEN3009, during the trial, and for 12 months after the last dose of GEN3009, a woman must be either not of childbearing potential or of childbearing potential and practicing a highly effective method of birth control, and must have a negative serum beta-human chorionic gonadotropin (beta-hCG) and urine pregnancy test at screening.
  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.

Exclusion Criteria:

  1. Prior treatment with a CD37-targeting agent.
  2. Prior allogeneic Hematopoietic Stem Cell Transplantation (HSCT).
  3. Autologous HSCT within 3 months before the first dose of GEN3009.
  4. Treatment with an anti-cancer biologic including anti-CD20 therapy, radio-conjugated or toxin-conjugated antibody or chimeric antigen receptor (CAR) T-cell therapy within 4 weeks or 5 half-lives, whichever is shorter, before the first dose of GEN3009.
  5. Chemotherapy or radiation therapy within 2 weeks of the first dose of GEN3009.
  6. Treatment with an investigational drug or an invasive investigational medical device within 4 weeks or 5 half-lives, whichever is shorter, prior to the first dose of GEN3009.
  7. Autoimmune disease or other diseases that require permanent or high-dose immunosuppressive therapy.
  8. Received a cumulative dose of corticosteroids more than the equivalent of 250 mg of prednisone within the 2-week period before the first dose of GEN3009.
  9. Has uncontrolled intercurrent illness.
  10. Toxicities from previous anti-cancer therapies have not resolved to baseline levels or to Grade 1 or less except for alopecia and peripheral neuropathy.
  11. Primary central nervous system (CNS) lymphoma or known CNS involvement at screening.
  12. Known past or current malignancy other than inclusion diagnosis,
  13. Has had major surgery within 3 weeks before screening or will not have fully recovered from surgery, or has major surgery planned during the time the subject is expected to participate in the trial (or within 4 weeks after the last dose of GEN3009).
  14. Known history/positive serology for hepatitis B.
  15. Known medical history or ongoing hepatitis C infection that has not been cured.
  16. HIV tested positive at screening.
  17. Is 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 GEN3009.
  18. Is a man who plans to father a child while enrolled in this trial or within 12 months after the last dose of GEN3009.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Genmab A/S Trial Information +4570202728 clinicaltrials@genmab.com
Listed Location Countries  ICMJE Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04358458
Other Study ID Numbers  ICMJE GCT3009-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Genmab
Study Sponsor  ICMJE Genmab
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Genmab
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP