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Trial of the Safety and Efficacy of Epcoritamab in Japanese Subjects With R/R B-NHL

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: NCT04542824
Recruitment Status : Recruiting
First Posted : September 9, 2020
Last Update Posted : November 23, 2022
Sponsor:
Collaborator:
AbbVie
Information provided by (Responsible Party):
Genmab

Brief Summary:

The trial is an open-label, multi-center safety and preliminary efficacy trial of epcoritamab in Japanese patients with relapsed, progressive or refractory B-cell lymphomas and Japanese patients with B-cell lymphomas that have achieved partial response (PR) or complete response (CR) following prior SOC. The trial consists of two parts: Part 1, dose escalation (phase 1), and Part 2, expansion (phase 2).

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 Japanese patients with relapsed, progressive or refractory B-cell lymphoma and Japanese patients with B-cell lymphomas that have achieved partial response (PR) or complete response (CR).

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.

Part 2 of the trial will be initiated once the RP2D has been determined in Part 1. In Part 2, epcoritamab is investigated as a monotherapy and in combination with other standard of care (SOC) agents.


Condition or disease Intervention/treatment Phase
Diffuse Large B Cell Lymphoma High-grade B-cell Lymphoma Primary Mediastinal Large B Cell Lymphoma Follicular Lymphoma Marginal Zone Lymphoma Small Lymphocytic Lymphoma Biological: epcoritamab (monotherapy) Biological: epcoritamab Drug: rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone Drug: gemcitabine and oxaliplatin Biological: epcoritamab (maintenance) Drug: rituximab and lenalidomide Phase 1 Phase 2

Detailed Description:

All participants in the trial will receive epcoritamab, as monotherapy or in combination with SOC. The following regimens will be investigated in Part 2:

Arm 1: epcoritamab monotherapy in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL)

Arm 2: epcoritamab + rituximab and lenalidomide (R2) in patients with R/R FL

Arm 3: epcoritamab + rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with previously untreated DLBCL with high risk features

Arm 4: epcoritamab + gemcitabine and oxaliplatin (GemOx) in patients with R/R DLBCL who either failed prior autologous hematopoietic stem cell transplantation (ASCT), or are ineligible for autologous HSCT.

Arm 5: epcoritamab maintenance in patients with FL who achieve a complete response (CR) or a partial response (PR) following 1L/2L SOC treatment

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 102 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

Part 1: Sequential Assignment

Part 2: Parallel Group Assignment

Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Safety and Preliminary Efficacy of Epcoritamab (GEN3013; DuoBody®-CD3×CD20) in Japanese Subjects With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma - A Phase 1/2, Open-Label, Dose-Escalation Trial With Expansion Cohorts
Actual Study Start Date : August 20, 2020
Estimated Primary Completion Date : December 30, 2024
Estimated Study Completion Date : December 30, 2024


Arm Intervention/treatment
Experimental: arm 1: epcoritamab
In subjects with DLBCL/FL
Biological: epcoritamab (monotherapy)
Epcoritamab will be administered subcutaneously in cycles of 4 weeks (i.e. 28 days)
Other Name: GEN3013; DuoBody®-CD3xCD20

Experimental: arm 2: epcoritamab + rituximab + lenalidomide
In subjects with relapsed/refractory FL
Biological: epcoritamab
Epcoritamab will be administered in combination with the respective SOC chemotherapy followed by epcoritamab monotherapy.
Other Name: GEN3013; DuoBody®-CD3xCD20

Drug: rituximab and lenalidomide
28-day cycles.
Other Name: R2

Experimental: arm 3: epcoritamab + rituximab + cyclophosphamide+ doxorubicin+ vincristine + prednisone
In subjects with previously untreated DLBCL
Biological: epcoritamab
Epcoritamab will be administered in combination with the respective SOC chemotherapy followed by epcoritamab monotherapy.
Other Name: GEN3013; DuoBody®-CD3xCD20

Drug: rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone
21-day cycles
Other Name: R-CHOP

Experimental: arm 4: epcoritamab + gemcitabine + oxaliplatin
In subjects with relapsed/refractory DLBCL
Biological: epcoritamab
Epcoritamab will be administered in combination with the respective SOC chemotherapy followed by epcoritamab monotherapy.
Other Name: GEN3013; DuoBody®-CD3xCD20

Drug: gemcitabine and oxaliplatin
28-day cycles
Other Name: Gemox

Experimental: arm 5: epcoritamab maintenance
In subjects with FL in complete response (CR) or in partial response (PR) following first line or second line SOC treatment
Biological: epcoritamab (maintenance)
28-day cycle for Cycle 1 and then 56-day cycle from Cycle 2 through 13
Other Name: GEN3013; DuoBody®-CD3xCD20




Primary Outcome Measures :
  1. Part 1: Incidence and severity of Adverse Events (AEs) [ Time Frame: From first dose until the end of the safety follow-up period (60 days after last dose) ]
    Treatment emergent AEs.

  2. Part 1: Incidence of Dose limiting toxicities (DLTs) [ Time Frame: DLTs are assessed during the first cycle (28 days) in each cohort ]
    To determine the RP2D and the MTD, if reached.

  3. Part 2, Arm 1: Objective response rate (ORR) [ Time Frame: From 6 weeks after enrollment until treatment discontinuation, assessed up to 3 years ]
    Antitumor activity as measured by the ORR according to Lugano classification

  4. Part 2, Arms 2-4: Incidence of DLTs [ Time Frame: DLTs are assessed during the first cycle (28 days) in arms 2-4 ]
  5. Part 2, Arms 2-5: Incidence and severity of AEs [ Time Frame: From first dose until the end of the safety follow-up period (60 days after last dose) ]
    Treatment emergent AEs (TEAEs)


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 (ADAs) [ Time Frame: From first dose until treatment discontinuation, expected average of 1 year ]
  10. Part 1 and Part 2, Arm1: Number of participants with clinically significant shifts from baseline in clinical laboratory parameters [ Time Frame: From first dose until treatment discontinuation, expected average of 1 year ]
    Clinical laboratory parameters assessed: biochemistry, hematology

  11. Part 2, Arm1: 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.

  12. Part 1 and Part 2, arms 2-5: ORR [ Time Frame: Approximately 3 years after the last subject's first dose ]
    Defined as proportion of participants who have a PR or CR following treatment with epcoritamab. Determined by the Lugano response criteria.

  13. Both parts: CR rate [ Time Frame: Approximately 3 years after the last subject's first dose ]
    Defined as proportion of participants with CR. Determined by the Lugano response criteria (both parts) and by the LYRIC response criteria (Part 2, arm 1). Response/disease progression in Part 2, arm 1 is reviewed by the IRC.

  14. Both parts: Duration of Response (DOR) [ Time Frame: Approximately 3 years after the last subject'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 (Part 2, arm 1). Response/disease progression in the expansion part is reviewed by the IRC.

  15. Both parts: Progression Free Survival (PFS) [ Time Frame: Approximately 3 years after the last subject'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 (Part 2, arm 1). Response/disease progression in the expansion part is reviewed by the IRC.

  16. Part 2: Duration of CR (DoCR) [ Time Frame: Approximately 3 years after the last subject'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

  17. Part 2: Time to Response (TTR) [ Time Frame: Approximately 3 years after the last subject'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.

  18. Part 1 and Part 2 arm 1: Time to next anti-lymphoma therapy (TTNT) [ Time Frame: Approximately 3 years after the last subject's first dose ]
    Calculated as time to date of initiation of new anti-lymphoma therapy.

  19. Both parts: Overall Survival (OS) [ Time Frame: Approximately 3 years after the last subject's first dose ]
    Defined as time to death.



Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Main Inclusion Criteria:

• Must be at least 20 years of age, inclusive

• Japanese subjects

• CD20 positivity at representative tumor biopsy

  1. Part 1:

    • Diffuse large B-cell lymphoma (de novo or histologically transformed)
    • High-grade B-cell lymphoma
    • Primary mediastinal large B-cell lymphoma
    • Follicular lymphoma
    • Marginal zone lymphoma (nodal, extranodal of mucosa-associated lymphoid tissue, or splenic)
    • Small lymphocytic lymphoma
  2. Part 2 :

    Arm 1:

    • Diffuse large B-cell lymphoma (de novo or histologically transformed)
    • Follicular lymphoma grade 1-3A
    • Relapsed or refractory disease and previously treated with at least 2 lines of systemic antineoplastic therapy including at least 1 anti-CD20 mAb-containing therapy.
    • Measurable disease by CT, MRI or PET-CT scan

    Arm 2:

    • R/R FL grade 1, 2 or 3a, stage II, III, or IV, without evidence of transformation.

    • Previously treated with at least 1 prior anti-neoplastic agent, including anti-CD20 antibody
    • Must have a need for treatment initiation based on symptoms and/or disease burden (GELF criteria)
    • Eligible to receive R2 per investigator determination

    Arm 3:

    • One of following confirmed histologies (de novo or histologically transformed from FL or nodal marginal zone lymphoma) :

      o DLBCL, NOS

      o "Double-hit" or "triple-hit" DLBCL

      • FL Grade 3B.
      • T-cell/histiocyte rich LBCL
    • International Prognostic Index (IPI) score ≥3
    • No prior therapy for DLBCL or FL G3B other than nodal biopsy, corticosteroids, or palliative radiotherapy.
    • Eligible to receive R-CHOP per investigator determination

    Arm 4:

    • One of following confirmed histologies (de novo or histologically transformed from FL or nodal marginal zone lymphoma) including:

      o DLBCL, NOS.

      o "Double-hit" or "triple-hit" DLBCL

      o FL Grade 3B.

      o T-cell/histiocyte rich LBCL

    • Relapsed or refractory to at least one prior therapy including at least one prior anti-CD20 antibody.
    • Either failed prior autologous hematopoietic stem cell transplantation (ASCT), or ineligible for autologous HSCT
    • Eligible to receive GemOx per investigator determination

    Arm 5:

    • History of histologically confirmed CD20+ FL Grade 1-3a without evidence of transformation.

    • In CR or PR per Lugano criteria following first-line or second-line treatment with SOC regimen, including anti-CD20 antibody, and last dose of SOC within 6 months prior to enrollment

    Main Exclusion Criteria:

    • Primary CNS lymphoma or CNS involvement by lymphoma at screening

    • Subjects not eligible for high dose therapy with autologous hematopoietic stem cell transplantation due to personal choice, social issues, or similar

    • Known clinically significant cardiac disease

    • Chronic ongoing infectious diseases requiring treatment (excluding prophylactic treatment)

    Exclusion criteria for Part 2, Arms 2 through 5:

    Arm 2:

    • FL Grade 3b

    • Histologic evidence of transformation to an aggressive lymphoma

    • Contraindication to rituximab or lenalidomide
    • Unwilling or unable to take aspirin prophylaxis or prophylactic anticoagulant as clinically indicated

    Arm 3:

    • Contraindication to any of the individual drugs of the R-CHOP regimen

    Arm 4:

    • Contraindication to any of the individual drugs of the GemOx regimen

    Arm 5:

    • FL Grade 3b
    • Histologic evidence of transformation to an aggressive lymphoma

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): NCT04542824


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

Locations
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Sponsors and Collaborators
Genmab
AbbVie
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Responsible Party: Genmab
ClinicalTrials.gov Identifier: NCT04542824    
Other Study ID Numbers: GCT3013-04 / EPCORE(TM) NHL-3
JapicCTI no 205408 ( Registry Identifier: JAPIC )
First Posted: September 9, 2020    Key Record Dates
Last Update Posted: November 23, 2022
Last Verified: November 2022
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
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, B-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
Gemcitabine
Prednisone
Cyclophosphamide
Rituximab
Doxorubicin
Oxaliplatin
Vincristine
Lenalidomide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents