Trial of the Safety and Efficacy of Epcoritamab in Japanese Subjects With Relapsed or Refractory (R/R) B-Cell Non-Hodgkin Lymphoma (R/R B-NHL)

NCT ID: NCT04542824

Last Updated: 2026-01-06

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 78 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-20
• Study Completion Date: 2027-09-30

Brief Summary

The trial is an open-label, multi-center safety and preliminary efficacy trial of epcoritamab (EPKINLY™) in Japanese participants with relapsed, progressive or refractory B-cell lymphomas and Japanese participants with B-cell lymphomas that have achieved partial response (PR) or complete response (CR) following prior standard of care (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 participants with relapsed, progressive or refractory B-cell lymphoma and Japanese participants with B-cell lymphomas that have achieved PR or CR.

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.

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 SOC agents.

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 participants with R/R FL

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

Arm 4: epcoritamab + gemcitabine and oxaliplatin (GemOx) in participants 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 participants with FL who achieve a CR or a PR following first line (1L)/second line (2L) SOC treatment

Conditions

Diffuse Large B Cell Lymphoma; High-grade B-cell Lymphoma; Primary Mediastinal Large B Cell Lymphoma; Follicular Lymphoma; Marginal Zone Lymphoma; Small Lymphocytic Lymphoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 3: Epcoritamab + Rituximab + Cyclophosphamide+ Doxorubicin+ Vincristine + Prednisone

In participants with previously untreated DLBCL

Group Type: EXPERIMENTAL

Epcoritamab

Intervention Type: BIOLOGICAL

Epcoritamab will be administered in combination with the respective SOC chemotherapy followed by epcoritamab monotherapy.

Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone

Intervention Type: DRUG

21-day cycles

Arm 4: Epcoritamab + Gemcitabine + Oxaliplatin

In participants with relapsed/refractory DLBCL

Group Type: EXPERIMENTAL

Epcoritamab

Intervention Type: BIOLOGICAL

Epcoritamab will be administered in combination with the respective SOC chemotherapy followed by epcoritamab monotherapy.

Gemcitabine and oxaliplatin

Intervention Type: DRUG

28-day cycles

Arm 5: Epcoritamab Maintenance

In participants with FL in CR or in PR following 1L or 2L SOC treatment

Group Type: EXPERIMENTAL

Epcoritamab (maintenance)

Intervention Type: BIOLOGICAL

28-day cycle for Cycle 1 and then 56-day cycle from Cycle 2 through 13

Arm 2: Epcoritamab + Rituximab + Lenalidomide

In participants with R/R FL

Group Type: EXPERIMENTAL

Epcoritamab

Intervention Type: BIOLOGICAL

Epcoritamab will be administered in combination with the respective SOC chemotherapy followed by epcoritamab monotherapy.

Rituximab and lenalidomide

Intervention Type: DRUG

28-day cycles.

Arm 1: Epcoritamab

In participants with DLBCL/FL.

Group Type: EXPERIMENTAL

Epcoritamab (monotherapy)

Intervention Type: BIOLOGICAL

Epcoritamab will be administered subcutaneously in cycles of 4 weeks (i.e. 28 days)

Interventions

Epcoritamab (monotherapy)

Epcoritamab will be administered subcutaneously in cycles of 4 weeks (i.e. 28 days)

Intervention Type: BIOLOGICAL

Epcoritamab

Epcoritamab will be administered in combination with the respective SOC chemotherapy followed by epcoritamab monotherapy.

Intervention Type: BIOLOGICAL

Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone

21-day cycles

Intervention Type: DRUG

Gemcitabine and oxaliplatin

28-day cycles

Intervention Type: DRUG

Epcoritamab (maintenance)

28-day cycle for Cycle 1 and then 56-day cycle from Cycle 2 through 13

Intervention Type: BIOLOGICAL

Rituximab and lenalidomide

28-day cycles.

Intervention Type: DRUG

Other Intervention Names

GEN3013; DuoBody®-CD3xCD20; EPKINLY™; GEN3013; DuoBody®-CD3xCD20; EPKINLY™; R-CHOP; GemOx; GEN3013; DuoBody®-CD3xCD20; EPKINLY™; R2

Eligibility Criteria

Inclusion Criteria

• Must be at least 20 years of age, inclusive

• Japanese participants

• 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 monoclonal antibody (mAb)-containing therapy.
• Measurable disease by computed tomography (CT), magnetic resonance imaging (MRI) or positron emission tomography (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 (Groupe d'Etude des Lymphomes Folliculaires [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, not otherwise specified (NOS)

• "Double-hit" or "triple-hit" DLBCL
• FL Grade 3B.
• T-cell/histiocyte rich large B-cell lymphoma (LBCL)
• International Prognostic Index (IPI) score ≥3
• No prior therapy for DLBCL or FL grade 3B (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

• FL Grade 3B.
• 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 hematopoietic stem-cell transplantation (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

Exclusion Criteria

• Primary central nervous system (CNS) lymphoma or CNS involvement by lymphoma at screening

• Participants 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)

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

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AbbVie

INDUSTRY

Sponsor Role: collaborator

Genmab

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Tohoku University Hoaspital

Sendai, Miyagi, Japan

Aichi Cancer Center Hospital

Aichi, , Japan

NHO Nagoya Medical Center

Aichi, , Japan

National Cancer Center Hospital East

Chiba, , Japan

Matsuyama Red Cross Hospital

Ehime, , Japan

National Hospital Organization Kyushu Cancer Center

Fukuoka, , Japan

Fukushima Medical University Hospital

Fukushima, , Japan

Kagoshima University Hospital

Kagoshima, , Japan

Kyoto University Hospital

Kyoto, , Japan

Kindai University Hospital

Osaka, , Japan

Osaka University Hospital

Osaka, , Japan

Cancer Institute Hospital of JFCR

Tokyo, , Japan

National Cancer Center Hospital

Tokyo, , Japan

Tokyo Medical University Hospital

Tokyo, , Japan

Yamagata University Hospital

Yamagata, , Japan

Countries

Japan

References

Izutsu K, Akahane D, Toubai T, Saito T, Mishima Y, Fujisaki T, Nishikori M, Kumode T, Suehiro Y, Ishitsuka K, Conlon R, Takahashi A, D'Angelo Mansson B, Favaro E, Fukuhara N. Subcutaneous epcoritamab monotherapy in Japanese patients with relapsed or refractory follicular lymphoma: primary results of the EPCORE NHL-3 trial. Leuk Lymphoma. 2025 Oct;66(10):1913-1921. doi: 10.1080/10428194.2025.2525983. Epub 2025 Jul 9.

Reference Type: DERIVED

PMID: 40632620 (View on PubMed)

Other Identifiers

JapicCTI-205408

Identifier Type: REGISTRY

Identifier Source: secondary_id

jRCT2080225312

Identifier Type: REGISTRY

Identifier Source: secondary_id

GCT3013-04

Identifier Type: -

Identifier Source: org_study_id