A Study to Evaluate Change in Disease Activity of Subcutaneous (SC) Epcoritamab Combined With Intravenous and Oral Rituximab, Cyclophosphamide, Doxorubicin Hydrochloride, Vincristine, and Prednisone (R-CHOP) or R-CHOP in Adult Participants With Newly Diagnosed Diffuse Large B-Cell Lymphoma (DLBCL)

B-cell Lymphoma is an aggressive and rare cancer of a type of immune cells (a white blood cell responsible for fighting infections). The purpose of this study is to assess the change in disease activity of epcoritamab when combined with intravenous and oral rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone (R-CHOP) or R-CHOP in adult participants globally with diffuse large b-cell lymphoma (DLBCL). Change in disease activity will be assessed.

Epcoritamab is an investigational drug being developed for the treatment of DLBCL. Study doctors put the participants in groups called treatment arms. Participants will receive epcoritamab combined with R-CHOP, followed by epcoritamab or R-CHOP followed by rituximab will be explored. Approximately 900 adult participants with with newly diagnosed DLBCL will be enrolled in the study in approximately 315 sites in globally.

In the Arm 1, participants will receive subcutaneous epcoritamab combined with intravenous and oral R-CHOP followed by subcutaneous epcoritamab in 21-day cycles. In the Arm 2, participants will receive intravenous and oral R-CHOP followed by intravenous rituximab in 21-day cycles.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, questionnaires and side effects.


Eligibility Criteria:
Inclusion Criteria:

* Planned to receive treatment with 6 cycles of standard rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone (R-CHOP) per investigator determination.
* Must have newly diagnosed, histologically confirmed CD20+ diffuse large b-cell lymphoma \[DLBCL\] (de novo or histologically transformed from a diagnosis of follicular lymphoma) at most recent representative tumor biopsy based on the pathology report, with a World Health Organization (WHO) 2016 classification and including:

  * DLBCL, Not Otherwise Specified (NOS).
  * High grade B-cell lymphoma with MYC and BCL-2 and/or BCL-6 rearrangement with DLBCL morphology.
  * T-cell/histiocyte-rich large B-cell lymphoma.
  * Epstein Barr virus-positive DLBCL, NOS.
  * Follicular lymphoma Grade 3b.

Note: The local pathology report must be available at Screening to support CD20+ DLBCL histology.

Composite/intermediate histology with any of the following components is not allowed: high grade B-cell lymphoma, NOS; Hodgkin's lymphoma; primary mediastinal (thymic) large B-cell lymphoma; Burkitt; plasmablastic lymphoma or any CD20- lymphoma, such as anaplastic lymphoma kinase-positive large B-cell lymphoma, human herpesvirus type 8-positive DLBCL, or primary effusion lymphoma.

* Availability of archival or fresh or paraffin embedded tissue at Screening.
* Must have an IPI score of 2-5. The number of participants with IPI 2 will not exceed approximately 30% of the overall sample size.
* Must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2 prior to initiating R-CHOP treatment. Note that participant with an initial ECOG performance status \>= 3 may be screened if pre-phase treatment is planned. Participant may be eligible if ECOG performance status were to improve to 0-2 during pre-phase treatment.
* Has at least one target lesion defined as:

  * \>= 1 measurable nodal lesion (long axis \> 1.5 cm ) or \>= 1 measurable extra-nodal lesion (long axis \> 1 cm) on computed tomography (CT) scan or magnetic resonance imaging (MRI). AND
  * Positron emission tomography (PET)-positive on PET-CT scan.
* Laboratory values meeting the criteria laid out in the protocol.
* Left ventricular ejection fraction must be \>= 50% by multi-gated acquisition or transthoracic echocardiography at Screening.

Exclusion Criteria:

* History of prior systemic anti-lymphoma therapy for diagnosed diffuse large b-cell lymphoma (DLBCL) including any definitive radiotherapy with curative intent\] other than corticosteroids with or without vincristine during prephase treatment, or non-curative intent palliative radiotherapy with the stipulation that radiated lesions cannot be selected as target lesion for response assessment.
* Clinically significant cardiovascular disease as per the protocol.