Trial of the Safety and Efficacy of Epcoritamab in Japanese Subjects With R/R B-NHL (EPCORE™ NHL-3)

April 2, 2024 updated by: Genmab

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

The trial is an open-label, multi-center safety and preliminary efficacy trial of epcoritamab (EPKINLY™) 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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Estimated)

102

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Japan
      • Chuo Ku, Japan
        • National Cancer Center Hospital
      • Fukuoka-shi, Japan
        • National Hospital Organization Kyushu Cancer Center
      • Fukushima-shi, Japan
        • Fukushima Medical University Hospital
      • Kagoshima-shi, Japan
        • Kagoshima University Hospital
      • Kashiwa-shi, Japan
        • National Cancer Center Hospital East
      • Koto-Ku, Japan
        • Cancer Institute Hospital of JFCR
      • Kyoto-shi, Japan
        • Kyoto University Hospital
      • Matsuyama-shi, Japan
        • Matsuyama Red Cross Hospital
      • Nagoya-shi, Japan
        • Aichi Cancer Center Hospital
      • Nagoya-shi, Japan
        • NHO Nagoya Medical Center
      • Osaka, Japan
        • Kindai University Hospital
      • Shinjuku-Ku, Japan
        • Tokyo Medical University Hospital
      • Suita-shi, Japan
        • Osaka University Hospital
      • Yamagata-shi, Japan
        • Yamagata University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • GEN3013
  • DuoBody®-CD3xCD20
  • EPKINLY™
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 Names:
  • GEN3013
  • DuoBody®-CD3xCD20
  • EPKINLY™
Drug: rituximab and lenalidomide
28-day cycles.
Other Names:
  • 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 Names:
  • GEN3013
  • DuoBody®-CD3xCD20
  • EPKINLY™
Drug: rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone
21-day cycles
Other Names:
  • 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 Names:
  • GEN3013
  • DuoBody®-CD3xCD20
  • EPKINLY™
Drug: gemcitabine and oxaliplatin
28-day cycles
Other Names:
  • 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 Names:
  • GEN3013
  • DuoBody®-CD3xCD20
  • EPKINLY™

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
From first dose until the end of the safety follow-up period (60 days after last dose)
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.
DLTs are assessed during the first cycle (28 days) in each cohort
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
From 6 weeks after enrollment until treatment discontinuation, assessed up to 3 years
Part 2, Arms 2-4: Incidence of DLTs
Time Frame: DLTs are assessed during the first cycle (28 days) in arms 2-4
DLTs are assessed during the first cycle (28 days) in arms 2-4
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)
From first dose until the end of the safety follow-up period (60 days after last dose)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
From first dose until treatment discontinuation, expected average of 1 year
Both parts: Maximum (peak) plasma concentration (Cmax)
Time Frame: From first dose until treatment discontinuation, expected average of 1 year
From first dose until treatment discontinuation, expected average of 1 year
Both parts: Time to reach Cmax (Tmax)
Time Frame: From first dose until treatment discontinuation, expected average of 1 year
From first dose until treatment discontinuation, expected average of 1 year
Both parts: Pre-dose (trough) concentrations (Cthrough)
Time Frame: From first dose until treatment discontinuation, expected average of 1 year
From first dose until treatment discontinuation, expected average of 1 year
Both parts: Total body clearance of drug from the plasma (CL)
Time Frame: From first dose until treatment discontinuation, expected average of 1 year
From first dose until treatment discontinuation, expected average of 1 year
Both parts: Volume of distribution (Vd)
Time Frame: From first dose until treatment discontinuation, expected average of 1 year
From first dose until treatment discontinuation, expected average of 1 year
Both parts: Elimination half-life (t 1/2)
Time Frame: From first dose until treatment discontinuation, expected average of 1 year
From first dose until treatment discontinuation, expected average of 1 year
Both parts: AUC from Time 0 to Infinity (AUCinf)
Time Frame: From first dose until treatment discontinuation, expected average of 1 year
From first dose until treatment discontinuation, expected average of 1 year
Both parts: Incidence of Anti-Drug-Antibodies (ADAs)
Time Frame: From first dose until treatment discontinuation, expected average of 1 year
From first dose until treatment discontinuation, expected average of 1 year
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
From first dose until treatment discontinuation, expected average of 1 year
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.
From first dose until the end of the safety follow-up period (60 days after last dose)
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.
Approximately 3 years after the last subject's first dose
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.
Approximately 3 years after the last subject's first dose
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.
Approximately 3 years after the last subject's first dose
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.
Approximately 3 years after the last subject's first dose
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
Approximately 3 years after the last subject's first dose
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.
Approximately 3 years after the last subject's first dose
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.
Approximately 3 years after the last subject's first dose
Both parts: Overall Survival (OS)
Time Frame: Approximately 3 years after the last subject's first dose
Defined as time to death.
Approximately 3 years after the last subject's first dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Genmab

Collaborators

AbbVie

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 20, 2020

Primary Completion (Estimated)

December 30, 2024

Study Completion (Estimated)

December 30, 2024

Study Registration Dates

First Submitted

August 25, 2020

First Submitted That Met QC Criteria

September 2, 2020

First Posted (Actual)

September 9, 2020

Study Record Updates

Last Update Posted (Actual)

April 3, 2024

Last Update Submitted That Met QC Criteria

April 2, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GCT3013-04
  • JapicCTI no 205408 (Registry Identifier: JAPIC)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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