Subcutaneous Epcoritamab Versus Standard of Care in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma: Phase 3 EPCORE DLBCL-1 Trial

Introduction:
Patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) have a poor prognosis. Epcoritamab is a subcutaneously administered bispecific antibody that induces killing of malignant CD20 B cells by binding to CD3 on T cells and CD20 on B cells. Previously, epcoritamab 48 mg has shown a tolerable safety profile and substantial antitumor activity, including a complete response rate of 39% and an overall response rate of 63% in patients with R/R large B-cell lymphoma (N=157, phase 2 expansion cohort of EPCORE NHL-1 trial). These data are encouraging and support further evaluation of subcutaneous epcoritamab in R/R DLBCL. Herein we describe the design, methods, and status of an ongoing trial assessing epcoritamab versus standard of care (SOC) in patients with R/R DLBCL.
Methods:
EPCORE DLBCL-1, a global, randomized, open-label phase 3 trial, is evaluating the efficacy of epcoritamab versus investigator’s choice of SOC (either rituximab, gemcitabine, and oxaliplatin [R-GemOx] or bendamustine and rituximab [BR]) in adults with certain CD20 R/R aggressive B-cell NHLs. The following lymphomas are included: (1) DLBCL, not otherwise specified, including de novo or histologically transformed from follicular lymphoma (FL); (2) T-cell/histiocyte-rich large B-cell lymphoma; (3) “double- or triple-hit” DLBCL, defined as high-grade B-cell lymphoma with and and/or translocations, including de novo or histologically transformed from FL; and (4) FL grade 3B. Eligible patients must have received ≥1 line of prior chemotherapy administered with an anti-CD20 antibody and ECOG performance status 0–2. In addition, patients must have had prior failure of autologous stem cell transplant (ASCT) or be ineligible to receive ASCT, though prior CAR T-cell therapy is allowed at least 100 d from randomization. Approximately 480 patients will be assigned (with 1:1 randomization) to receive subcutaneous epcoritamab or investigator’s choice of SOC (R-GemOx or BR, administered intravenously). Patients assigned to receive epcoritamab 48 mg will be treated until disease progression or unacceptable toxicity in 28-d cycles: QW in cycles 1–3, Q2W in cycles 4–9, and Q4W in cycles ≥10. Those assigned to receive SOC will be treated with R-GemOx Q2W for a maximum of four 28-d cycles (8 doses) or BR Q3W for a maximum of six 21-d cycles (12 doses of bendamustine, 6 doses of rituximab). The primary endpoint is overall survival, with key secondary endpoints including progression-free survival, overall response rate, duration of response, time to response, and safety.
Status:
Enrollment is ongoing in AT, AU, BE, CA, CN, DE, DK, ES, FI, FR, HU, IL, IT, JP, KR, NL, NO, PL, RU, SE, SG, TR, TW, UK, and US, as is expansion into additional countries (NCT04628494).