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First-in-Human (FIH) Trial in Patients With Relapsed, Progressive or Refractory B-Cell Lymphoma (EPCORE™ NHL-1)

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ClinicalTrials.gov Identifier: NCT03625037
Recruitment Status : Recruiting
First Posted : August 10, 2018
Last Update Posted : August 8, 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 and efficacy trial of epcoritamab, an antibody also known as EPKINLY™ and GEN3013 (DuoBody®-CD3xCD20). The trial consists of 3 parts:

  • a dose-escalation part (Phase 1, first-in-human (FIH))
  • an expansion part (Phase 2a)
  • a dose-optimization part (Phase 2a)

Condition or disease Intervention/treatment Phase
Diffuse Large B-cell Lymphoma (DLBCL) High-grade B-cell Lymphoma (HGBCL) Primary Mediastinal Large B-cell Lymphoma (PMBCL) Follicular Lymphoma (FL) Mantle Cell Lymphoma (MCL) Small Lymphocytic Lymphoma (SLL) Marginal Zone Lymphoma (MZL) Biological: Epcoritamab Phase 1 Phase 2

Expanded Access : An investigational treatment associated with this study has been approved for sale to the public.   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 RP2D.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 786 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
Actual Study Start Date : June 26, 2018
Estimated Primary Completion Date : January 2025
Estimated Study Completion Date : April 2029

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
  • EPKINLY™


Outcome Measures
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Primary Outcome Measures :
  1. Escalation part: Incidence of Dose Limiting Toxicities (DLTs) [ Time Frame: 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) as assessed by CTCAE v5.0. Abnormal laboratory values are reported as AEs per protocol.

  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: Number of participants with cytokine release syndrome (CRS) events [ Time Frame: From first dose until 7 days after second full dose (Day 28 for DLBCL/MCL; Day 35 for FL) ]
  5. Optimization part: Percentage of participants with =>Grade 2 CRS events [ Time Frame: From first dose until 7 days after second full dose (Day 28 for DLBCL/MCL; Day 35 for FL) ]

Secondary Outcome Measures :
  1. Escalation & Optimization parts: 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.

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

  3. All 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.

  4. 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.

  5. All 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.

  6. Expansion & Optimization parts: 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.

  7. All 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.

  8. All 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.

  9. All 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.

  10. Optimization part: Incidence of DLTs [ Time Frame: From first dose until 7 days after second full dose (Day 28 for DLBCL/MCL; Day 35 for FL) ]
  11. Optimization part: Number of participants with CRS events [ Time Frame: From Day 15 (DLBCL/MCL) or Day 22 (FL) until up to 1 year after the last participant's first dose ]
  12. Optimization part: Percentage of participants with =>Grade 2 CRS events [ Time Frame: From Day 15 (DLBCL/MCL) or Day 22 (FL) until up to 1 year after the last participant's first dose ]
  13. Optimization part: Number of participants with CRS events [ Time Frame: From first dose until up to 1 year after the last participant's first dose ]
  14. Optimization part: Percentage of participants with =>Grade 2 CRS events [ Time Frame: From first dose until up to 1 year after the last participant's first dose ]
  15. Expansion & Optimization parts: 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 as assessed by CTCAE v5.0. Abnormal laboratory values are reported as AEs per protocol.

  16. All 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 ]
  17. All parts: AUC from Time 0 to Infinity (AUCinf) [ Time Frame: From first dose until treatment discontinuation, expected average of 1 year. ]
  18. All parts: Maximum (peak) plasma concentration (Cmax) [ Time Frame: From first dose until treatment discontinuation, expected average of 1 year ]
  19. All parts: Time to reach Cmax (Tmax) [ Time Frame: From first dose until treatment discontinuation, expected average of 1 year ]
  20. All parts: Pre-dose (trough) concentrations (Cthrough) [ Time Frame: From first dose until treatment discontinuation, expected average of 1 year ]
  21. All parts: Elimination half-life (t 1/2) [ Time Frame: From first dose until treatment discontinuation, expected average of 1 year ]
  22. All parts: Total body clearance of drug from the plasma (CL) [ Time Frame: From first dose until treatment discontinuation, expected average of 1 year ]
  23. All parts: Volume of distribution (Vd) [ Time Frame: From first dose until treatment discontinuation, expected average of 1 year ]
  24. All parts: Incidence of anti-drug antibodies (ADA) [ Time Frame: From first dose until up to 1 year after the last participant's first dose ]
  25. Expansion & Optimization parts: Percentage of participants with Minimal Residual Disease (MRD) negativity status [ Time Frame: From first dose until up to 1 year after the last participant's first dose ]
    Defined as proportion of participants with at least one MRD negative result.

  26. Expansion & Optimization parts: Duration of MRD negative status [ Time Frame: From first dose until up to 1 year after the last participant's first dose ]
    Defined as the number of days from the first documentation of MRD negative status to the date of MRD status change (not MRD negative).

  27. 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.


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. DLBCL - de novo or transformed
    2. HGBCL
    3. PMBCL
    4. FL
    5. MCL
    6. SLL
    7. MZL (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 & Optimization Parts

  • Documented CD20 positive mature B cell neoplasm or CD20+ MCL
  • DLBCL, de novo or transformed (including double hit or triple hit)
  • PMBCL
  • FL grade 3B
  • Histologic confirmed FL
  • MZL
  • SLL
  • MCL (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

Main Exclusion Criteria - All 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

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

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 of Results:

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 )
NL64317.078.17 ( Registry Identifier: CCMO )
241053 ( Other Identifier: IRAS ID; UK Research Summaries Database )
First Posted: August 10, 2018    Key Record Dates
Last Update Posted: August 8, 2023
Last Verified: August 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
Lymphoma, Large B-Cell, Diffuse
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
 Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Leukemia, B-Cell
Leukemia, Lymphoid
Leukemia
Chronic Disease
Disease Attributes
Pathologic Processes