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Trial record 1 of 1 for:    GCT3013-01
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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 : Active, not recruiting
First Posted : August 10, 2018
Last Update Posted : June 4, 2024
Sponsor:
Collaborator:
AbbVie
Information provided by (Responsible Party):
Genmab

Brief Summary:

The purpose of this trial is to measure the following in participants with relapsed and/or refractory B-cell lymphoma who receive epcoritamab, an antibody also known as EPKINLY™ and GEN3013 (DuoBody®-CD3xCD20):

  • The dose schedule for epcoritamab
  • The side effects seen with epcoritamab
  • What the body does with epcoritamab once it is administered
  • What epcoritamab does to the body once it is administered
  • How well epcoritamab works against relapsed and/or refractory B-cell lymphoma

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 (OPT) (Phase 2a)

The trial time for each participant depends on which trial part the participant enters:

  • For the dose-escalation part, each participant will be in the trial for approximately 1 year, which is made up of 21 days of screening, 6 months of treatment (the total time of treatment may be different for each participant), and 6 months of follow-up (the total time of follow-up may be different for each participant).
  • For the expansion and dose-OPT parts, each participant will be in the trial for approximately 1.5 years, which is made up of 21 days of screening, 1 year of treatment (the total time of treatment may be different for each participant), and 6 months of follow-up (the total time of follow-up may be different for each participant).

Participation in the study will require visits to the sites. During the first month, participants must visit every day or every few days, depending on which trial part the participant enters. After that, participants must visit weekly, every other week, once a month, and once every 2 months, as trial participation ends.

All participants will receive active drug, and no participants will be given placebo.


Condition or disease Intervention/treatment Phase
DLBCL High-grade B-cell Lymphoma (HGBCL) Primary Mediastinal Large B-cell Lymphoma (PMBCL) FL 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 participants with relapsed or refractory B-cell lymphoma.

In the expansion part, additional participants 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-OPT part will evaluate alternative priming and intermediate dose regimens of epcoritamab in participants with:

  • Diffuse large B-cell lymphoma (DLBCL)
  • Follicular lymphoma (FL)
  • Mantle cell lymphoma (MCL)

All participants will receive epcoritamab at the RP2D.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 666 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 : March 2025
Estimated Study Completion Date : January 2029


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™




Primary Outcome Measures :
  1. Dose-Escalation: Dose Limiting Toxicity (DLT) [ Time Frame: During the first cycle (28 days) in each Dose-OPT Part DLBCL, FL and MCL ]
    To determine the MTD and/or RP2D to be studied in the Expansion part. DLT will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.

  2. Dose-Escalation: Number of Participants with Adverse Events (AEs) [ Time Frame: From first dose until the end of the safety follow-up period (Up to 1 year) ]
    An AE is any untoward medical occurrence in a clinical trial participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product.

  3. Expansion and Dose-OPT MCL: Overall Response Rate (ORR) [ Time Frame: Up to 1.5 years ]
    ORR is defined as the percentage of participants achieving complete response (CR) or partial response (PR) based on Lugano criteria as assessed by independent review committee (IRC).

  4. Dose-OPT DLBCL, FL and MCL: Percentage of Participants with =>Grade 2 Cytokine Release Syndrome (CRS) Events and All Grade CRS Events [ Time Frame: From first dose until 7 days after second full dose (Day 28 for DLBCL; Day 35 for FL; Day 28-35 for MCL) ]
    CRS will be graded based on American Society for Transplantation and Cellular Therapy (ASTCT) criteria.


Secondary Outcome Measures :
  1. Dose-Escalation: Number of Participants with Anti-lymphoma Activity of Epcoritamab [ Time Frame: Up to 1 year ]
    Anti-lymphoma activity will be evaluated as number of participants with resolution of constitutional symptoms, reduction in tumor size, objective, and best response (ORR, CR and PR).

  2. Dose-Escalation: DOR [ Time Frame: Up to 1 year ]
    DOR is defined as the time from the first documentation of response (CR or PR) to the date of PD or death, whichever occurs earlier as assessed by the investigator.

  3. Expansion: DOR [ Time Frame: Up to 1.5 years ]
    DOR is defined as the time from the first documentation of response (CR or PR) to the date of PD or death, whichever occurs earlier based on Lugano criteria assessed by IRC.

  4. Expansion Part: Changes in Lymphoma Symptoms as Measured by the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) [ Time Frame: Up to 1.5 year ]
    Change from baseline in health-related quality of life over time and in relation to treatment will be evaluated using FACT-Lym scale.

  5. Dose-OPT DLBCL and FL: Percentage of Participants with >=Grade 2 CRS Events and All Grade CRS Events Following First Full Dose [ Time Frame: Up to 1.5 years ]
    CRS will be graded based on ASTCT criteria.

  6. Dose-OPT DLBCL and FL: Percentage of Participants with >=Grade 2 CRS Events and All Grade CRS Events Overall [ Time Frame: Up to 1.5 years ]
    CRS will be graded based on ASTCT criteria.

  7. Dose-OPT DLBCL and FL: ORR [ Time Frame: Up to 1.5 years ]
    ORR is defined as the percentage of participants achieving CR or PR assessed by investigator.

  8. Dose-OPT DLBCL and FL: CR Rate [ Time Frame: Up to 1.5 years ]
    CR rate is defined as the percentage of participants with CR assessed by investigator.

  9. Dose-OPT DLBCL and FL: Duration of CR (DoCR) [ Time Frame: Up to 1.5 years ]
    DoCR is defined as the time from the first documentation of CR to the date of PD or death, whichever occurs earlier assessed by investigator.

  10. Dose-OPT DLBCL and FL: Progression-Free Survival (PFS) [ Time Frame: Up to 1.5 years ]
    PFS is defined as the time from Day 1 of Cycle 1 to first documented PD or death due to any cause, whichever occurs earlier assessed by investigator.

  11. Dose-OPT DLBCL and FL: DLT [ Time Frame: During the first cycle (28 days) in each Dose-OPT Part (DLBCL, FL and MCL) ]
    To determine the MTD and/or RP2D to be studied in the expansion part. DLT will be graded according to NCI-CTCAE version 5.0.

  12. Dose-OPT MCL: Time to Complete Response (TTCR) [ Time Frame: Up to 1.5 years ]
    TTCR is defined as the time from Day 1 of Cycle 1 to first documentation of complete response based on Lugano criteria and LYRIC as assessed by IRC.

  13. Dose-OPT DLBCL, FL and MCL: DOR [ Time Frame: Up to 1.5 years ]
    DOR is defined as the time from the first documentation of response (CR or PR) to the date of PD or death, whichever occurs earlier based on Lugano criteria assessed by investigator.

  14. Dose-Escalation and Dose-OPT DLBCL, FL and MCL: Pre-dose Values of Epcoritamab [ Time Frame: Predose and postdose at multiple timepoints of each Cycle (Cycle length=28 days) ]
  15. Dose-Escalation, Expansion Part and Dose-OPT MCL: PFS [ Time Frame: Dose-Escalation: Up to 1 year; Expansion and Dose-OPT Part (MCL): 1.5 years ]
    PFS is defined as the time from Day 1 of Cycle 1 to first documented PD or death due to any cause, whichever occurs earlier based on Lugano criteria assessed by IRC.

  16. Expansion and Dose-OPT MCL: CR Rate [ Time Frame: Up to 1.5 years ]
    CR rate is defined as the percentage of participants with CR based on Lugano criteria as assessed by IRC.

  17. Expansion and Dose-OPT MCL: DoCR [ Time Frame: Up to 1.5 years ]
    DoCR is defined as the time from the first documentation of CR to the date of PD or death, whichever occurs earlier based on Lugano criteria as assessed by IRC.

  18. Expansion and Dose-OPT MCL: ORR [ Time Frame: Up to 1.5 years ]
    ORR is defined as the percentage of participants achieving CR or PR based on lymphoma response to immunomodulatory therapy criteria (LYRIC) as assessed by IRC.

  19. Expansion and Dose-OPT MCL: Time to Response (TTR) [ Time Frame: Up to 1.5 years ]
    TTR is defined as the time from Day 1 of Cycle 1 to first documentation of objective tumor response (PR or better) earlier based on Lugano criteria as assessed by IRC.

  20. Expansion and Dose-OPT MCL: CR Rate [ Time Frame: Up to 1.5 years ]
    CR rate is defined as the percentage of participants with CR based on LYRIC as assessed by IRC.

  21. Expansion and Dose-OPT MCL: PFS [ Time Frame: Up to 1.5 years ]
    PFS is defined as the time from Day 1 of Cycle 1 to first documented PD or death due to any cause, whichever occurs earlier based on LYRIC assessed by IRC.

  22. Expansion and Dose-OPT MCL: DOR [ Time Frame: Up to 1.5 years ]
    DOR is defined as the time from the first documentation of response (CR or PR) to the date of PD or death, whichever occurs earlier based on LYRIC assessed by IRC.

  23. Expansion and Dose-OPT MCL: DoCR [ Time Frame: Up to 1.5 years ]
    DoCR is defined as the time from the first documentation of CR to the date of PD or death, whichever occurs earlier based on LYRIC as assessed by IRC.

  24. Expansion and Dose-OPT MCL: TTR [ Time Frame: Up to 1.5 years ]
    TTR is defined as the time from Day 1 of Cycle 1 to first documentation of objective tumor response (PR or better) earlier based on LYRIC as assessed by IRC.

  25. Expansion and Dose-OPT DLBCL, FL and MCL: Number of Participants with AEs [ Time Frame: Up to 7 years and 6 months ]
    An AE is any untoward medical occurrence in a clinical trial participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product.

  26. Expansion and Dose-OPT DLBCL, FL and MCL: Rate of Minimal Residual Disease (MRD) Negativity [ Time Frame: Up to 1.5 years ]
    MRD is defined as percentage of participants with at least 1 MRD negative result.

  27. All Parts: Number of Participants with CRS Events [ Time Frame: Up to Day 1 of Cycle 12 (Cycle length=28 days) ]
    CRS will be graded based on ASTCT criteria.

  28. All Parts: Immunophenotyping for Absolute T-cell and B-cell [ Time Frame: Up to Day 1 of Cycle 12 (Cycle length=28 days) ]
    Number of cells will be reported for absolute T-cells and B-cells.

  29. All Parts: T-Cell Activation and Exhaustion Marker [ Time Frame: Up to 7 years and 6 months ]
    T-Cell Activation and Exhaustion Marker (CD69, CD25, and PD-1) will be measured using flow cytometry.

  30. All Parts: Total Body Clearance of Epcoritamab from the Plasma (CL) [ Time Frame: Predose and postdose at multiple timepoints of each cycle (Cycle length=28 days) ]
  31. All Parts: Area under Curve (AUC) of Epcoritamab [ Time Frame: Predose and postdose at multiple timepoints of each cycle (Cycle length=28 days) ]
  32. All Parts: Maximum (peak) Plasma Concentration (Cmax) of Epcoritamab [ Time Frame: Predose and postdose at multiple timepoints of each cycle (Cycle length=28 days) ]
  33. All Parts: Time to Reach Cmax of Epcoritamab [ Time Frame: Predose and postdose at multiple timepoints of each cycle (Cycle length=28 days) ]
  34. All Parts: Half Life of Epcoritamab (t1/2) [ Time Frame: Predose and postdose at multiple timepoints of each cycle (Cycle length=28 days) ]
  35. All Parts: Number of Participants with Anti-drug Antibody (ADA) [ Time Frame: Up to 7 years and 6 months ]
    Plasma samples will be screened for antibodies binding to epcoritamab, and for confirmed positive samples, the titer against the two specific arms of epcoritamab will be reported.

  36. All Parts: Time to Next Anti-lymphoma Therapy (TTNT) [ Time Frame: Dose-Escalation: Up to 1 year; Expansion and Dose-OPT Part (DLBCL, FL and MCL): Up to 1.5 years ]
    TTNT is defined as the time from Day 1 of Cycle 1 to first recorded administration of subsequent anti-lymphoma therapy or death due to any cause, whichever occurs earlier.

  37. All Parts: Overall survival (OS) [ Time Frame: Dose-Escalation: Up to 1 year; Expansion and Dose-OPT Part DLBCL, FL and MCL: Up to 1.5 years ]
    OS is defined as the time from Day 1 of Cycle 1 to death.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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 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.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0,1 or 2.
  • Participants must have measurable disease by CT, MRI or Positron emission tomography-Computed tomography (PET-CT) scan
  • Acceptable renal function.
  • Acceptable liver function.

Main Inclusion Criteria - Expansion & Dose-OPT 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 (HSCT) 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 Creatinine clearance (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). Participants 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 Informed consent form (ICF).
  • Pregnancy or breast feeding.
  • Participant 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 participant.
  • Contraindication to all uric acid lowering agents.

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


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


Locations
Show Show 85 study locations
Sponsors and Collaborators
Genmab
AbbVie
Investigators
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Study Director: Study Official Genmab
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 )
2023-504802-12-00 ( EU Trial (CTIS) Number )
First Posted: August 10, 2018    Key Record Dates
Last Update Posted: June 4, 2024
Last Verified: June 2024
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, B-Cell, Marginal Zone
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
Hematologic Diseases
Chronic Disease
Disease Attributes
Pathologic Processes