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

Main Inclusion Criteria:

• Must be at least 20 years of age, inclusive

• Japanese subjects

• CD20 positivity at representative tumor biopsy

Part 1:

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

Part 2 :

Arm 1:

1. Diffuse large B-cell lymphoma (de novo or histologically transformed)
2. Follicular lymphoma grade 1-3A
3. 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.
4. 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.

1. Previously treated with at least 1 prior anti-neoplastic agent, including anti-CD20 antibody
2. Must have a need for treatment initiation based on symptoms and/or disease burden (GELF criteria)
3. 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

1. FL Grade 3B.
2. T-cell/histiocyte rich LBCL
3. International Prognostic Index (IPI) score ≥3
4. No prior therapy for DLBCL or FL G3B other than nodal biopsy, corticosteroids, or palliative radiotherapy.
5. 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

1. Relapsed or refractory to at least one prior therapy including at least one prior anti-CD20 antibody.
2. Either failed prior autologous hematopoietic stem cell transplantation (ASCT), or ineligible for autologous HSCT
3. 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

1. Contraindication to rituximab or lenalidomide
2. 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:

1. FL Grade 3b
2. Histologic evidence of transformation to an aggressive lymphoma