The purpose of this trial is to measure the safety and effectiveness of epcoritamab (EPKINLY™), either by itself or together with other therapies, when treating participants with B-cell non-Hodgkin Lymphoma (B-NHL). The aim of the first part of the trial is to identify the most appropriate dose of epcoritamab, and the aim of the second part of the trial is to assess the selected epcoritamab dose in a larger group of participants with B-NHL. All participants in this trial will receive either epcoritamab alone, or epcoritamab combined with another standard treatment regimen, with a total of 10 different treatment arms being studied.

Trial details include:

• The treatment duration for each participant depends upon which arm of treatment they are assigned to.
• The visit frequency for each participant depends upon which arm of treatment they are assigned to, but will be weekly to start for all participants, then will decrease to either: every 2 weeks, or every 3 weeks, or every 4 weeks, or every 8 weeks.
• All participants will receive active drug; no one will be given placebo.

Participants who receive treatment with epcoritamab will have it injected right under the skin. Participants will receive a different regimen of epcoritamab depending upon which arm of treatment they are assigned.

Participants who receive standard treatments will have intravenous (IV) infusions and/or oral administration of those treatments. Participants will receive a different standard treatment regimen depending upon which arm of treatment they are assigned.

A Phase 1b/2, open-label, multinational, interventional trial to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics/biomarkers, immunogenicity, and preliminary efficacy of epcoritamab in combination with other standard of care (SOC) agents in participants with B-NHL.

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

• Arm 1: epcoritamab + rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in participants with previously untreated diffuse large B-cell lymphoma (DLBCL)
• Arm 2: epcoritamab + rituximab and lenalidomide (R2) in participants with relapsed/refractory (R/R) follicular lymphoma (FL)
• Arm 3: epcoritamab + rituximab and bendamustine (BR) in participants with previously untreated FL
• Arm 4: epcoritamab + rituximab, cytarabine, dexamethasone, and oxaliplatin/ carboplatin (R-DHAX/C) in participants with R/R DLBCL eligible for autologous stem cell transplant (ASCT)
• Arm 5: epcoritamab + gemcitabine and oxaliplatin (GemOx) in participants with R/R DLBCL ineligible for ASCT due to age, performance status (PS), or comorbidity
• Arm 6: epcoritamab + R2 in participants with previously untreated FL
• Arm 7: epcoritamab maintenance in participants with FL who achieve a complete response (CR) or a partial response (PR) following first or second line SOC treatment
• Arm 8: epcoritamab + reduced dose of R-CHOP (R mini-CHOP) in participants with previously untreated DLBCL who are ineligible to receive full-dose anthracycline
• Arm 9: epcoritamab + lenalidomide for second-line treatment in participants with R/R FL who progressed within 24 months of initiation of first-line anti-CD20-containing immunochemotherapy
• Arm 10: epcoritamab + rituximab, ifosfamide, carboplatin, and etoposide phosphate (R-ICE) in participants with R/R DLBCL eligible for ASCT

The trial consists of two parts: Part 1 ('Dose Escalation') and Part 2 ('Dose Expansion'). The primary objective of Part 1 is safety, and it includes Arm 1-5 and Arm 10. Part 2 includes all 10 arms (Arm 1-10) and the primary goal of all arms, except Arm 7, is preliminary efficacy. For Arm 7, the primary goal is safety. Participants in Arm 1-5 and Arm 10 can only participate in either Part 1 or Part 2. Dose Limiting Toxicities (DLTs) will be assessed in Part 1 and for a selected number of participants in Arm 8 during a 28-day period (safety run-in). The arms are conducted in parallel.

Key Inclusion Criteria

1. Measurable disease defined as ≥1 measurable nodal lesion (long axis >1.5 cm and short axis >1.0 cm) or ≥1 measurable extra-nodal lesion (long axis >1.0 cm) on computed tomography (CT) or magnetic resonance imaging (MRI). Applies to all arms except arm 7.
2. Eastern Cooperative Oncology Group (ECOG) PS score of 0, 1 or 2
3. Acceptable organ function at screening
4. CD20-positive non-Hodgkin lymphoma (NHL) at most recent representative tumor biopsy
5. If of childbearing potential participant must practicing a highly effective method of birth control
6. A man who is sexually active with a woman of childbearing potential must agree to use a barrier method of birth control

Arm 1:

• Newly diagnosed DLBCL
• DLBCL, not otherwise specified (NOS)
• "Double-hit" or "triple-hit" DLBCL
• FL Grade 3B

Arm 2: R/R FL

Arm 3: Newly diagnosed, previously untreated FL grade 1-3A

Arm 4:

• Documented R/R DLBCL and eligible for HDT-ASCT
• DLBCL, NOS
• "Double-hit" or "triple-hit" DLBCL
• FL Grade 3B

Arm 5:

• Documented R/R DLBCL and ineligible for HDT-ASCT
• DLBCL, NOS
• "Double-hit" or "triple-hit" DLBCL
• FL Grade 3B

Arm 6: Newly diagnosed, previously untreated FL grade 1-3A

Arm 7:

• FL Grade 1-3A
• If PR or CR per Lugano criteria following first-line or second-line treatment with SOC regimen, and last dose of SOC within 6 months prior to enrollment.

Arm 8:

• Newly diagnosed DLBCL who are not fit to receive full-dose anthracycline
• T-cell/histiocyte rich DLBCL
• "Double-hit" or "triple-hit" DLBCL
• FL Grade 3B

Arm 9:

• R/R FL
• Progressed within 24 months of initiating first-line treatment

Arm 10:

• Documented R/R DLBCL and eligible for HDT-ASCT
• DLBCL, NOS
• "Double-hit" or "triple-hit" DLBCL
• FL Grade 3B

Key Exclusion Criteria

1. Chemotherapy, radiation therapy, or major surgery within 4 weeks prior to the first dose of epcoritamab
2. Any prior treatment with a bispecific antibody targeting CD3 and CD20.
3. Treatment with CAR-T therapy within 100 days prior to first dose of epcoritamab
4. Clinically significant cardiovascular disease
5. Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results
6. CNS lymphoma or known CNS involvement by lymphoma at screening as confirmed by MRI/CT scan of the brain and, if clinically indicated, by lumbar puncture
7. Positive tests for hepatitis B virus or hepatitis C virus indicating acute or chronic infection
8. Known history of seropositivity of human immunodeficiency virus (HIV)
9. Active tuberculosis or history of completed treatment for active tuberculosis within the past 12 months
10. Neuropathy > grade 1
11. Receiving immunostimulatory agent
12. Prior allogeneic HSCT
13. Current seizure disorder requiring anti-epileptic therapy

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.