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GEN3013, Epcoritamab Trial in Patients With Relapsed, Progressive or Refractory B-Cell Lymphoma EPCORE™ NHL-1

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03625037
Recruitment Status : Recruiting
First Posted : August 10, 2018
Last Update Posted : February 24, 2023
Sponsor:
Collaborator:
AbbVie
Information provided by (Responsible Party):
Genmab

Study Description
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Brief Summary:
The trial is a global, multi-center safety trial of Epcoritamab, an antibody also known as GEN3013 (DuoBody®-CD3xCD20). The trial consists of three parts: a dose-escalation part (Phase 1, first-in-human (FIH)), an expansion part (Phase 2a) and a dose optimization part (Phase 2a)

Condition or disease Intervention/treatment Phase
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 Biological: Epcoritamab Phase 1 Phase 2

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

Detailed Description:

The purpose of the dose-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 epcoritamab in patients with relapsed, progressive or refractory B-Cell Lymphoma.

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

The dose optimization part will evaluate alternative priming and intermediate dose regimens of epcoritamab. All patients will receive Epcoritamab at the already established full dose.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 700 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2, Open-Label Safety Trial of GEN3013 in Patients With Relapsed, Progressive or Refractory B-Cell Lymphoma EPCORE™NHL-1
Actual Study Start Date : June 26, 2018
Estimated Primary Completion Date : October 30, 2023
Estimated Study Completion Date : July 1, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arms and Interventions
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Arm Intervention/treatment
Experimental: Epcoritamab
Epcoritamab will be administered by subcutaneous injections in cycles of 28 days
 Biological: Epcoritamab
Administered as specified in the treatment arm.
Other Names:
  • GEN3013
  • DuoBody®-CD3xCD20


Outcome Measures
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Primary Outcome Measures :
  1. Escalation part: Incidence of Dose Limiting Toxicities (DLTs) [ Time Frame: Assessed during the first cycle (28 days) in each cohort. ]
    To determine the RP2D and the MTD, if reached.

  2. Escalation part: Incidence and severity of Adverse Events (AEs) [ Time Frame: From first dose until the end of the safety follow-up period (4 weeks after last dose) ]
    Treatment-emergent AEs (TEAEs)

  3. Expansion part: Objective Response Rate (ORR) [ Time Frame: From first dose until up to 1 year after the last participant's first dose ]
    Defined as proportion of participants who have a partial or complete response (PR or CR) following treatment with epcoritamab. Determined by the Lugano response criteria, assessed by the Independent Review Committee (IRC).

  4. Optimization Part: • Determine whether an alternative priming/intermediate dose regimen may reduce CRS risk [ Time Frame: per subject 5 weeks after the first dose of Epcoritamab. per cohort 5 weeks after the last dosed patient in a cohort first dose of Epcoritamab ]
    Rate of ≥ Grade 2 CRS events and all grade CRS events from first dose of epcoritamab through 7 days following administration of the second full dose of epcoritamab


Secondary Outcome Measures :
  1. Both parts: Area-under-the-concentration-time curve from Time 0 to Time of last dose (AUClast) [ Time Frame: From first dose until treatment discontinuation, expected average of 1 year ]
  2. Both parts: AUC from Time 0 to Infinity (AUCinf) [ Time Frame: From first dose until treatment discontinuation, expected average of 1 year. ]
  3. Both parts: Maximum (peak) plasma concentration (Cmax) [ Time Frame: From first dose until treatment discontinuation, expected average of 1 year ]
  4. Both parts: Time to reach Cmax (Tmax) [ Time Frame: From first dose until treatment discontinuation, expected average of 1 year ]
  5. Both parts: Pre-dose (trough) concentrations (Cthrough) [ Time Frame: From first dose until treatment discontinuation, expected average of 1 year ]
  6. Both parts: Total body clearance of drug from the plasma (CL) [ Time Frame: From first dose until treatment discontinuation, expected average of 1 year ]
  7. Both parts: Volume of distribution (Vd) [ Time Frame: From first dose until treatment discontinuation, expected average of 1 year ]
  8. Both parts: Elimination half-life (t 1/2) [ Time Frame: From first dose until treatment discontinuation, expected average of 1 year ]
  9. Both parts: Incidence of anti-drug antibodies (ADA) [ Time Frame: From first dose until up to 1 year after the last participant's first dose ]
  10. Escalation part: ORR [ Time Frame: From first dose until up to 1 year after the last participant's first dose ]
    Defined as proportion of participants who have a PR or CR following treatment with epcoritamab. Determined by the Lugano response criteria.

  11. Escalation phase: PR [ Time Frame: From first dose until up to 1 year after the last participant's first dose ]
    Determined by the Lugano response criteria.

  12. Expansion part: Time to Response (TTR) [ Time Frame: From first dose until up to 1 year after the last participant's first dose ]
    Defined as time to first documentation of objective tumor response (PR or better). Determined by the Lugano and LYRIC response criteria, assessed by the IRC.

  13. Both parts: Duration of Response (DOR) [ Time Frame: From first dose until up to 1 year after the last participant's first dose ]
    Defined as time from first documentation of response (CR or PR) to the date of progression of disease (PD) or death, whichever occurs earlier. Determined by the Lugano response criteria (both parts) and by the LYRIC response criteria (expansion part). Response/disease progression in the expansion part is reviewed by the IRC.

  14. Both parts: CR rate [ Time Frame: From first dose until up to 1 year after the last participant's first dose ]
    Defined as proportion of participants with CR. Determined by the Lugano response criteria (both parts) and by the LYRIC response criteria (expansion part). Response/disease progression in expansion part is reviewed by the IRC.

  15. Expansion part: Duration of CR (DoCR) [ Time Frame: From first dose until up to 1 year after the last participant's first dose ]
    Defined as time from first documentation of CR to the date of PD or death, whichever occurs earlier. Determined by the Lugano and LYRIC response criteria, assessed by the IRC.

  16. Both parts: Progression Free Survival (PFS) [ Time Frame: From first dose until up to 1 year after the last participant's first dose ]
    Defined as time to first documented PD or death due to any cause. Determined by the Lugano response criteria (both parts) and by the LYRIC response criteria (expansion part). Response/disease progression in the expansion part is reviewed by the IRC.

  17. Both parts: Time to next anti-lymphoma therapy (TTNT) [ Time Frame: From first dose until up to 1 year after the last participant's first dose ]
    Calculated as time to date of initiation of new anti-lymphoma therapy.

  18. Both parts: Overall Survival (OS) [ Time Frame: From first dose until up to 1 year after the last participant's first dose ]
    Defined as time to death.

  19. Expansion part: Rate and duration of Minimal Residual Disease (MRD) negative status [ Time Frame: From first dose until up to 1 year after the last participant's first dose ]
    Rate is defined as proportion of participants with at least one MRD- sample. Duration is defined as the number of days from the first documentation of MRD- to the date of MRD status change (not MRD-).

  20. Expansion part: Incidence and severity of AEs [ Time Frame: From first dose until the end of the safety follow-up period (60 days after last dose) ]
    TEAEs

  21. Expansion part: Number of participants with clinically significant shifts from baseline in clinical laboratory parameters [ Time Frame: From first dose until the end of the safety follow-up period (60 days after last dose) ]
    Clinical laboratory parameters assessed: biochemistry, hematology including immunophenotyping).

  22. Expansion part: Changes in lymphoma symptoms as measured by the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) [ Time Frame: From first dose until up to 1 year after the last participant's first dose ]
    Monitor change from baseline in health-related quality of life over time and in relation to treatment.

  23. Optimization Part: To evaluate safety and tolerability of alternative priming/intermediate dosing regimens [ Time Frame: 5 weeks after last patient dosed per cohort ]
    Rate of ≥ Grade 2 CRS events and all grade CRS events following first full dose Rate of ≥ Grade 2 CRS events and all grade CRS events overall Safety i.e., rate of DLTs [as applicable], rate of adverse events

  24. Optimization Part: Establish PK and pharmacodynamic profile after single and multiple doses [ Time Frame: Ongoing throughout optimization part Conduct ]
    PK paramters (predose and half life)

  25. Optimization Part: Evaluate immunogenicity [ Time Frame: Ongoing throughout optimization part Conduct ]
    Immunogenicity of epcoritamab

  26. Optimization Part: Evaluate clinical efficacy as determined by Lugano criteria [ Time Frame: Ongoing throughout optimization part Conduct and up to 1 year after LPFD ]
    ORR, CR, DOR, DoCR, PFS, TTNT, OS, MRD rate

  27. Optimization Part: Exploratory Objective: • To evaluate pharmacodynamic markers linked to the mechanism of action of epcoritamab [ Time Frame: Ongoing throughout optimization part Conduct and up to 1 year after LPFD ]
    Pharmacodynamic markers in blood samples


Eligibility Criteria
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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

Main Inclusion Criteria Escalation Part (recruitment completed)

  • 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 and Optimization Parts

  • 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

NOTE: Other protocol defined Inclusion criteria may apply.

Main Exclusion Criteria Escalation, Expansion and Optimization Parts

  • Primary central nervous system (CNS) lymphoma or CNS involvement by lymphoma at screening
  • Known past or current malignancy other than inclusion diagnosis
  • AST, and/or ALT >3 × upper limit of normal
  • Total bilirubin >1.5 × upper limit of normal, unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin
  • Estimated CrCl <45 mL/min
  • Known clinically significant cardiovascular disease
  • Ongoing active bacterial, viral, fungal, mycobacterial, parasitic, or other infection requiring systemic treatment (excluding prophylactic treatment). Past COVID-19 infection may be a risk factor
  • Confirmed history or current autoimmune disease or other diseases resulting in permanent immunosuppression or requiring permanent immunosuppressive therapy
  • Seizure disorder requiring therapy (such as steroids or anti-epileptics)
  • Any prior therapy with an investigational bispecific antibody targeting CD3 and CD20
  • Prior treatment with chimeric antigen receptor T-cell (CAR-T) therapy within 30 days prior to first epcoritamab administration
  • Eligible for curative intensive salvage therapy followed by high dose chemotherapy with HSCT rescue
  • Autologous HSCT within 100 days prior to first epcoritamab administration, or any prior allogeneic HSCT or solid organ transplantation
  • Active hepatitis B (DNA PCR-positive) or hepatitis C (RNA PCR-positive infection). Subjects with evidence of prior HBV but who are PCR-negative are permitted in
  • Known human immunodeficiency virus (HIV) infection
  • Exposed to live or live attenuated vaccine within 4 weeks prior to signing ICF
  • Pregnancy or breast feeding
  • Patient is known or suspected of not being able to comply with the study protocol or has any condition for which, participation would not be in the best interest of the patient
  • Contraindication to all uric acid lowering agents
Contacts and Locations
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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): NCT03625037


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

Locations
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Sponsors and Collaborators
Genmab
AbbVie
Investigators
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Principal Investigator: Pieternella Lugtenburg, MD, PhD Erasmus MC University Medical Center Rotterdam
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Genmab
ClinicalTrials.gov Identifier: NCT03625037    
Other Study ID Numbers: GCT3013-01
2017-001748-36 ( EudraCT Number )
First Posted: August 10, 2018    Key Record Dates
Last Update Posted: February 24, 2023
Last Verified: February 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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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Lymphoma
Lymphoma, B-Cell
Lymphoma, Mantle-Cell
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
 Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Leukemia, B-Cell
Leukemia, Lymphoid
Leukemia