A Phase 3, Randomized, Open-Label Study to Evaluate Safety and Efficacy of Epcoritamab in Combination with R-CHOP compared to R-CHOP in Subjects with Newly Diagnosed Diffuse Large B-Cell Lymphoma (DLBCL)

1.Adult male or female, >= 18 years old and < 80 years old, with a life
expectancy of >= 12 months.
2.Subject is planned to receive treatment with 6 cycles of standard R CHOP per
investigator determination.
3.Subject must have newly diagnosed, histologically confirmed CD20+ 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.
4.Availability of archival or freshly collected tumor tissue at Screening.
Archival paraffin-embedded tissue must be obtained within 8 weeks prior to
Cycle 1 Day 1.
5.Subject must have an IPI score of 2-5. The number of subjects with IPI 2
will be capped at 30% of the overall sample size.
6.Subject must have an Eastern Cooperative Oncology Group (ECOG) performance
status score of 0-2 prior to initiating R-CHOP treatment. Note that subject
with an initial ECOG performance status >= 3 may be screened if pre-phase
treatment is planned. Subject may be eligible if ECOG performance status were
to improve to 0-2 during pre phase treatment.
7.Subject 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 CT scan or MRI.
AND
- PET-positive on PET-CT scan.
8.Laboratory values meeting the following criteria within the screening period
prior to the first dose of study drug:
- Absolute neutrophil count (ANC) >= 0.5 × 109/L. (antibacterial prophylaxis per
institutional standard practice should be considered for participants with ANC
1.0 x 109/L).
- Hemoglobin >= 8 g/dL.
- Platelet count >= 75 × 109/L, or >= 25 × 109/L in the presence of bone marrow
involvement or splenomegaly
- Serum aspartate aminotransferase or serum alanine aminotransferase <= 3.0 ×
upper limit of normal (ULN) unless due to hepatic involvement of disease or
non-hepatic origin.
- Total bilirubin level <= 1.5 × ULN, ULN, unless the bilirubin rise is due to
Gilbert*s syndrome or lymphoma hepatobiliary involvement. Participants with
Gilbert*s syndrome must have a direct bilirubin of < 2 x ULN. Participants with
hepatobiliary involvement must have a total bilirubin of < 5 x ULN and without
a percutaneous biliary drain.
- Estimated creatinine clearance >= 40 mL/min, as calculated by the
Cockcroft-Gault formula with considerations for body weight.
- Prothrombin time/international normalized ratio/activated partial
thromboplastin time <= 1.5 × ULN, unless receiving anticoagulation.
9. Left ventricular ejection fraction must be >= 50% by multi gated acquisition
or transthoracic echocardiography at Screening.

1. Subject with history of prior systemic anti-lymphoma therapy for DLBCL
(including any definitive radiotherapy with curative intent) other than
corticosteroids with or without vincristine during pre-phase treatment, or
non-curative intent palliative radiotherapy with the stipulation that radiated
lesions cannot be selected as target lesion for response assessment.
2. Subject has clinically significant cardiovascular disease, including:
• Myocardial infarction or stroke within 6 months prior to enrollment.
OR
• The following conditions within 3 months prior to enrollment: unstable or
uncontrolled disease/condition related to or affecting cardiac function (e.g.,
unstable angina, congestive heart failure, New York Heart Association Class III
IV), uncontrolled cardiac arrhythmia
OR
• Screening 12-lead electrocardiogram (ECG) showing a baseline QT interval as
corrected by Fridericia*s formula (QTcF) > 470 msec (male) or > 480 sec
(female)
OR
• Other clinically significant electrocardiogram abnormalities within 6 months
prior to enrollment unless deemed stable and appropriately treated .