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GEN3013 Trial in Patients With Relapsed, Progressive or Refractory B-Cell Lymphoma

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ClinicalTrials.gov Identifier: NCT03625037
Recruitment Status : Recruiting
First Posted : August 10, 2018
Last Update Posted : July 28, 2021
Sponsor:
Collaborator:
AbbVie
Information provided by (Responsible Party):
Genmab

Tracking Information
First Submitted Date  ICMJE June 7, 2018
First Posted Date  ICMJE August 10, 2018
Last Update Posted Date July 28, 2021
Actual Study Start Date  ICMJE June 26, 2018
Estimated Primary Completion Date January 30, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 20, 2020)
  • Escalation: Adverse Events (safety) to determine the Recommended Phase 2 Dose RP2D [ Time Frame: Adverse Events are assessed during the first cycle (28 days) in each cohort. ]
    -Number of Adverse Events, treatment emergent AEs as assessed by CTCAE V5.0.
  • Escalation: Tolerability to determine the RP2D. [ Time Frame: DLTs are assessed during the first cycle (28 days) in each cohort. ]
    -Number of Dose limiting toxicities DLTs.
  • Expansion: Safety, Adverse Event AE Evaluation. [ Time Frame: Until 1 year after last patient enters the trial, through study completion. ]
    -Total number of AEs and number of treatment emergent AEs as assessed by CTCAE V5.0.
  • Expansion: Clinical Efficacy Evaluation. [ Time Frame: Until 1 year after last patient enters the trial, through study completion. ]
    -Antitumor activity as measured by the objective response rate according to Lugano classification
Original Primary Outcome Measures  ICMJE
 (submitted: August 9, 2018)
  • Dose Limiting Toxicities (DLTs) [ Time Frame: DLTs are assessed during the first cycle (28 days) in each cohort ]
    To determine recommended phase 2 dose of GEN3013
  • Adverse Events (AEs) [ Time Frame: AEs are collected throughout the study and up to 5 years after last patient first visit ]
    Number of participants with treatment-related adverse events as assessed by CTCAE v4.03
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 20, 2020)
  • Escalation and Expansion: Pharmacokinetic parameters Cmax [ Time Frame: Until 1 year after last patient enters the trial, through study completion. ]
    -PK, peak plasma concentration through concentration and half life.
  • Escalation and Expansion: Pharmacokinetic parameters AUC [ Time Frame: During the first 4 doses in each patient ]
    -Maximum concentration AUC 0-Clast, AUC 0-x and half life.
  • Escalation and Expansion: Immunogenicity-Anti Drug Antibody. [ Time Frame: Until 1 year after last patient enters the trial, through study completion. ]
    -ADA titers measured as positive or negative host immune response and compared to PK, safety and tumor response.
  • Expansion: Evaluate Patient Reported Outcomes EQ-5D-3L. [ Time Frame: Until 1 year after last patient enters the trial, through study completion. ]
    -EQ-5D-3L; a six item questionnaire measuring changes from baseline; item 1 addressing a summary of the 5 next being; mobility, self care, usual activity, pain/discomfort, anxiety depression. Measured on a scale from 0 to 100, 100 being best.
  • Expansion: Evaluate Patient Reported Outcomes FACT-Lym. [ Time Frame: Until 1 year after last patient enters the trial, through study completion. ]
    -FACT-Lym is a 2 module quality of life questionnaire measuring changes from baseline. FACT-G for quality of life and Lym a lymphoma specific questionnaire both using by a 5 point scale 0-4, 4 being best.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 9, 2018)
  • Cytokine measures [ Time Frame: During the first two cycles of treatment (1 cycle is 28 days), at unscheduled visits and up to 5 years after last patient first visit ]
    To establish tolerability of GEN3013 using an array-based ligand binding assay
  • Area-under-the-concentration-time curve (AUC0-C last) [ Time Frame: Through study completion and up to 5 years after last patient first visit ]
    To establish the PK profile of GEN3013 after single and multiple doses
  • Maximum Plasma Concentration (Cmax) of GEN3013 [ Time Frame: Through study completion and up to 5 years after last patient first visit ]
    To establish the PK profile of GEN3013 after single and multiple doses
  • Presence of neutralizing anti-drug antibodies (ADAs) in blood (positive/negative). [ Time Frame: Through study completion and up to 5 years after last patient first visit ]
    To evaluate immunogenicity of GEN3013
  • Reduction in tumor size [ Time Frame: Through study completion and up to 5 years after last patient first visit ]
    To evaluate the anti-lymphoma activity of GEN3013 as evaluated by Lugano classification (Cheson et al., 2014)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE GEN3013 Trial in Patients With Relapsed, Progressive or Refractory B-Cell Lymphoma
Official Title  ICMJE A Phase 1/2, Open-Label Safety Trial of GEN3013 in Patients With Relapsed, Progressive or Refractory B-Cell Lymphoma
Brief Summary The trial is an open-label, multi-center safety trial of epcoritamab GEN3013 (DuoBody®-CD3xCD20). The trial consists of two parts: a dose escalation part phase 1, first-in-human (FIH) and an expansion part phase 2a.
Detailed Description

The purpose of the escalation part of the trial is to determine the maximum tolerated dose and the recommended phase 2 dose (RP2D) as well as to establish the safety profile of epcoritamab GEN3013 (DuoBody®-CD3xCD20) in patients with relapsed, progressive or refractory B-Cell Lymphoma.

In the expansion part additional patients will be treated with epcoritamab with the RP2D and the purpose is to further explore and determine the safety and efficacy of epcoritamab.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Diffuse Large B-cell Lymphoma
  • High-grade B-cell Lymphoma
  • Primary Mediastinal Large B-cell Lymphoma
  • Follicular Lymphoma
  • Mantle Cell Lymphoma
  • Small Lymphocytic Lymphoma
  • Marginal Zone Lymphoma
Intervention  ICMJE Biological: Epcoritamab
Epcoritamab will be administered in cycles of 4 weeks i.e. 28 days.
Study Arms  ICMJE Experimental: Epcoritamab (GEN3013, DuoBody®-CD3xCD20)
Open label, single arm trial where Epcoritamab will be administered.
Intervention: Biological: Epcoritamab
Publications * Hutchings M, Mous R, Clausen MR, Johnson P, Linton KM, Chamuleau MED, Lewis DJ, Sureda Balari A, Cunningham D, Oliveri RS, Elliott B, DeMarco D, Azaryan A, Chiu C, Li T, Chen KM, Ahmadi T, Lugtenburg PJ. Dose escalation of subcutaneous epcoritamab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: an open-label, phase 1/2 study. Lancet. 2021 Sep 8. pii: S0140-6736(21)00889-8. doi: 10.1016/S0140-6736(21)00889-8. [Epub ahead of print]

*   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: February 11, 2021)
486
Original Estimated Enrollment  ICMJE
 (submitted: August 9, 2018)
110
Estimated Study Completion Date  ICMJE December 30, 2025
Estimated Primary Completion Date January 30, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Main Inclusion Criteria Escalation Part

  • Documented CD20+ mature B-cell neoplasm

    1. Diffuse large B-cell lymphoma - de novo or transformed
    2. High-grade B-cell lymphoma
    3. Primary mediastinal large B-cell lymphoma
    4. Follicular lymphoma
    5. Mantle cell lymphoma
    6. Small lymphocytic lymphoma
    7. Marginal zone lymphoma (nodal, extranodal or mucosa associated)
  • Relapsed, progressive and/or refractory disease following treatment with an anti-CD20 monoclonal antibody (e.g. rituximab) potentially in combination with chemotherapy and/or relapsed after autologous stem cell rescue.
  • ECOG performance status 0,1 or 2
  • Patients must have measurable disease by CT, MRI or PET-CT scan
  • Acceptable renal function
  • Acceptable liver function

Main Inclusion Criteria Expansion Part

  • Documented CD20 positive mature B cell neoplasm or CD20+ MCL
  • Diffuse large B cell lymphoma, de novo or transformed (including double hit or triple hit)
  • Primary mediastinal large B cell lymphoma
  • Follicular lymphoma grade 3B
  • Histologic confirmed follicular lymphoma
  • Marginal zone lymphomas
  • Small lymphocytic lymphoma
  • Mantle Cell Lymphoma (prior BTKi or intolerant to BTKi)
  • At least 2 therapies including an anti CD20 monoclonal antibody containing chemotherapy combination regimen
  • Either failed prior autologous hematopoietic stem cell transplantation or ineligible for autologous stem cell transplantation due to age or comorbidities
  • At least 1 measurable site of disease based on CT, MRI or PET-CT scan with involvement of 2 or more clearly demarcated lesions and or nodes
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 +45 70202728 clinicaltrials@genmab.com
Listed Location Countries  ICMJE Australia,   Canada,   Denmark,   Finland,   France,   Germany,   Italy,   Korea, Republic of,   Netherlands,   Poland,   Singapore,   Spain,   Sweden,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03625037
Other Study ID Numbers  ICMJE GCT3013-01
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
Plan to Share IPD: No
Responsible Party Genmab
Study Sponsor  ICMJE Genmab
Collaborators  ICMJE AbbVie
Investigators  ICMJE
Principal Investigator: Pieternella Lugtenburg, MD, PhD Erasmus MC University Medical Center Rotterdam
PRS Account Genmab
Verification Date July 2021

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