A Phase 3 Trial of Epcoritamab vs Investigator's Choice Chemotherapy in Relapsed/Refractory (R/R) Diffuse Large B-cell Lymphoma (DLBCL)

The trial is an open label, multi-center, global phase-3 randomized trial of epcoritamab. The goal of this randomized trial is to evaluate the efficacy of epcoritamab (GEN3013, DuoBody®-CD3xCD20) compared to investigator's choice of chemotherapy, in participants with relapsed, refractory DLBCL who have failed or are ineligible for high-dose chemotherapy and autologous stem cell transplant (HDT-ASCT). No change in chemotherapy is permitted for participants during the treatment phase of the trial.

Overall Survival (OS) is the primary endpoint in USA and in China, with the analysis population including all randomized participants. OS/Progression Free Survival (PFS) are dual-primary endpoints for rest of the world (outside US and China), with the analysis population also including all participants randomized.

The China sub-study of GCT3013-05 is registered under NCT07226752.

Main Inclusion Criteria:

• Relapsed or refractory disease and previously treated with at least 1 line of systemic antineoplastic therapy including anti-CD20 monoclonal antibody (mAb)-containing combination chemotherapy since lymphoma diagnosis
• One of the confirmed histologies below with CD20-positivity:

• DLBCL, not otherwise specified (NOS), including de novo or histologically transformed from follicular lymphoma (FL)
• "Double-hit" or "triple-hit" DLBCL (technically classified in World Health Organization (WHO) 2016 as high-grade B-cell lymphoma (HGBCL), with MYC and BCL2 and/or BCL6 translocations), including de novo or histologically transformed from FL
• FL Grade 3B
• T-cell/histiocyte-rich large B-cell lymphoma
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0-2
• Failed previous HDT-ASCT or not eligible for high-dose therapy autologous stem cell transplant (HDT-ASCT) at screening
• Participants must have detectable disease by positron emission tomography (PET) scan and measurable by computed tomography (CT) scan or magnetic resonance imaging (MRI)
• Acceptable renal and liver function
• Life expectancy >2 months on standard of care treatment

Main Exclusion Criteria:

• Primary Central Nervous System (CNS) tumor or known CNS involvement
• Any prior therapy with a bispecific antibody targeting CD3 and CD20
• Major surgery within 4 weeks prior to randomization
• Chemotherapy and other non-investigational antineoplastic agents (except CD20 mAbs) within 4 weeks or 5 half-lives (whichever is shorter) prior to randomization
• Any investigational drug within 4 weeks or 5 half-lives, whichever is longer, prior to randomization
• Autologous stem cell transplant (ASCT) within 100 days of randomization
• Treatment with chimeric antigen receptor T-cell (CAR-T) therapy within 100 days prior to randomization
• Seizure disorder requiring anti-epileptic therapy
• Clinically significant cardiac disease