Phase 3 trial (GCT3013-05) of epcoritamab versus standard of care in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

TPS7569 Background: Patients (pts) with DLBCL who are refractory to/or have relapsed (R/R) after treatment with chemotherapy and anti-CD20 monoclonal antibody (mAb) have a poor prognosis. There is a need for new treatment options to improve outcomes. Epcoritamab, a novel subcutaneous (SC) bispecific antibody, binds to CD3 on T-lymphocytes and CD20 on B-cell non-Hodgkin lymphoma (NHL) cells to induce potent and selective killing of malignant CD20+ B-cells. In an ongoing phase 1/2 dose-escalation trial in heavily pretreated pts with B-cell NHL (N = 68), epcoritamab demonstrated a tolerable safety profile and substantial single-agent anti-tumor activity, with a complete response (CR) rate of 55% and an overall response rate (ORR) of 91% in pts with R/R DLBCL (at ≥48 mg doses; n = 12) (NCT04663347; Hutchings, ASH, 2020). Furthermore, all 4 evaluable R/R DLBCL pts previously treated with chimeric antigen receptor T-cell (CAR-T) therapy achieved an objective response with 2 achieving CR. These encouraging data support the potential for epcoritamab to improve clinical outcomes in pts with R/R DLBCL. Here we describe the phase 3 trial of epcoritamab versus standard of care (SOC) treatments in pts with R/R DLBCL (NCT04628494). Methods: GCT3013-05 is a randomized, open-label, worldwide, multicenter, phase 3 study designed to evaluate the efficacy of epcoritamab versus investigator’s choice of SOC with R-GemOx (rituximab, gemcitabine, oxaliplatin) or BR (bendamustine, rituximab) in adults with R/R disease of one the following CD20+ B-cell NHL histologies: I) DLBCL, not otherwise specified including de novo DLBCL or DLBCL histologically transformed from follicular lymphoma; II) “double-hit” or “triple-hit” DLBCL (high-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 translocations); or III) follicular lymphoma grade 3B. Other key eligibility criteria include: ≥1 line of prior chemotherapy that included treatment with an anti-CD20 mAb, Eastern Cooperative Oncology Group performance status 0–2, and prior failure of/ineligibility for autologous stem cell transplantation. Prior CAR-T therapy is allowed. A total of 480 pts will be randomized 1:1 to receive either SC epcoritamab at the recommended phase 2 dose (28-day cycles; weekly, biweekly, or monthly schedule depending on cycle number) until disease progression or unacceptable toxicity; or up to 4 cycles of biweekly treatment with intravenous (IV) R-GemOx (8 doses); or up to 6 cycles of IV BR (6 doses; dosing every 3 weeks). The primary endpoint is overall survival. Key secondary endpoints include progression-free survival, ORR, duration of response, time to response, and safety. The study is currently enrolling in Australia, Belgium, Denmark, France, Spain, and will open for enrollment in additional countries. Clinical trial information: NCT04628494.