Background: The recent evolution of newer treatment options for patients with B-cell non-Hodgkin’s lymphoma (NHL) are encouraging, yet there remains a need for more effective and better tolerated therapies. Epcoritamab is a subcutaneously administered bispecific antibody that binds to CD3+ T cells and CD20+ B cells, inducing CD3+ T cells to kill CD20+ tumor B cells through a unique mechanism of action (MOA). In a dose-escalation study, epcoritamab monotherapy demonstrated a manageable safety profile and anti-tumor activity in pts with heavily pretreated R/R B-cell NHL (Hutchings et al, Lancet 2021). Promising preliminary results from the ongoing EPCORE NHL-2 trial (NTC04663347) were previously presented with epcoritamab in combination with other anti-neoplastic agents: epcoritamab + R-CHOP in previously untreated DLBCL (Belada et al, ASH 2021), and epcoritamab + rituximab and lenalidomide in R/R Follicular Lymphoma (Linton et al, ASH 2021). Novel combinations with epcoritamab may offer additional options for pts with B-cell NHL. An ongoing study (NCT02077166) evaluating ibrutinib, rituximab, and lenalidomide in R/R DLBCL has shown encouraging results; ibrutinib and lenalidomide may enhance T-cell activity and further potentiate the effects of epcoritamab in R/R DLBCL, particularly post-CAR-T. Investigation of pola-R-CHP compared to R-CHOP in pts with previously untreated DLBCL demonstrated an improvement in progression-free survival in the pola-R-CHP group (Tilly et al, NEJM 2022). Combining epcoritamab with the anti-neoplastic agents used in these studies, which have different MOAs and non-overlapping toxicities, may offer enhanced clinical benefit to pts with DLBCL.
Aims: To characterize the safety, tolerability, and preliminary efficacy profiles, and determine the recommended dose of epcoritamab co-administered with other anti-neoplastic agents as novel combinations in pts with B-cell NHL.
Methods: This open-label, global, multicenter study (EPCORE NHL-5) will evaluate subcutaneous administration of epcoritamab in novel combinations with other anti-neoplastic agents: Arm 1) epcoritamab + lenalidomide in R/R DLBCL; Arm 2) epcoritamab + ibrutinib and lenalidomide in R/R DLBCL; Arm 3) epcoritamab + pola-R-CHP in treatment-naïve DLBCL. Each arm will include a dose-escalation, followed by a dose-expansion phase. The primary objectives include assessment of dose-limiting toxicities and identification of the recommended dose for further investigation. Secondary endpoints include ORR, CR rate, DOR, PFS, TTR, and OS. Additional endpoints are safety, pharmacokinetics, and biomarker assessments. Pts must be ≥18 years old with an ECOG performance status 0 – 2. Other inclusion criteria are measurable disease by PET-CT and diagnosis of CD20+ DLBCL, including i) DLBCL, not otherwise specified; ii) “double-hit” or “triple-hit” DLBCL (high-grade B cell lymphoma), and iii) FL grade 3B. Pts must not have prior treatment with epcoritamab or other bispecific antibodies targeting CD3 and CD20 and no autologous SCT ≤3 months before screening.
Results: NA
Summary/Conclusion: Enrollment is planned to open in May 2022 in the United States and Israel, with additional countries in North America, Europe, and Asia for a total of ~100 sites.