Genmab has announced promising results from the Phase 1b/2 EPCORE® NHL-2 trial, which evaluated a fixed-duration regimen of epcoritamab, a T-cell engaging bispecific antibody, in combination with lenalidomide and rituximab (R2) in adult patients with relapsed or refractory (R/R) follicular lymphoma (FL). The study, which included 111 patients, reported an overall response rate (ORR) of 96% and a complete response (CR) rate of 87% after a median follow-up of two years. Additionally, the study showed a 21-month progression-free survival (PFS) rate of 80% and a two-year overall survival (OS) rate of 90%. These findings were presented at the 66th Annual Meeting of the American Society of Hematology (ASH) in December 2024.
Dr. Lorenzo Falchi, Lymphoma Specialist at Memorial Sloan Kettering Cancer Center, commented, Follicular lymphoma remains incurable for most patients, and those with relapsed or refractory disease, particularly those with high-risk features, need new therapeutic options. The durable responses seen in this trial are encouraging and support the continued investigation of epcoritamab in combination with rituximab and lenalidomide.
Additional data from the trial revealed that 89% of patients who achieved a complete response remained in CR at 18 months, indicating sustained benefits from the combination therapy.
Due to the global COVID-19 pandemic, 57% of patients in the study reported COVID-19 infections, with 13% discontinuing treatment due to the virus. Five cases of COVID-19 resulted in fatal treatment-emergent adverse events (TEAEs), including three deaths from COVID-19 and two from COVID-19 pneumonia. Other common TEAEs included neutropenia (62%) and cytokine release syndrome (CRS; 51%). CRS events were generally low grade (38% Grade 1, 12% Grade 2, 2% Grade 3) and primarily occurred following the first full dose of treatment, with all CRS cases resolving. One case of immune effector cell-associated neurotoxicity syndrome (ICANS) (Grade 1) was reported, but no CRS or ICANS cases led to treatment discontinuation.
Dr. Judith Klimovsky, Executive Vice President & Chief Development Officer at Genmab, said, “These long-term results are encouraging for patients with relapsed or refractory follicular lymphoma. The data underscore the potential of epcoritamab in FL and its role as a core therapy for B-cell malignancies, both as a monotherapy and in combination with standard treatments. We are excited to continue evaluating this combination in the ongoing Phase 3 EPCORE FL-1 trial.”
Epcoritamab, in combination with R2, has received breakthrough therapy designation (BTD) from the U.S. FDA for the treatment of adult patients with R/R FL who have received at least one prior line of therapy. The combination is being further studied in the ongoing Phase 3 EPCORE FL-1 trial (NCT05409066).
Epcoritamab + R2 has not been approved for use in R/R FL in the U.S., EU, or any other territory, and its safety and efficacy as a combination therapy in FL have not been established.
