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)

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

Main Inclusion Criteria:

• Must be at least 20 years of age, inclusive

• Japanese participants

• CD20 positivity at representative tumor biopsy

• 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
• 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

Main 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)

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