Genmab's Epcoritamab Shows Promising Results in First-Line Lymphoma Treatment with Fixed-Duration Therapy
Key Insights
Genmab announced updated clinical trial results for epcoritamab showing high response rates in first-line treatment of diffuse large B-cell lymphoma (search) (DLBCL) and follicular lymphoma (search) (FL) with fixed-duration therapy.
The EPCORE NHL-2 trial demonstrated overall response rates of 93-98% in newly diagnosed DLBCL patients, while achieving a 96% three-year overall survival rate in FL patients.
The EPCORE DLBCL-3 trial showed a 73% overall response rate in elderly DLBCL patients treated with epcoritamab monotherapy who were ineligible for standard chemotherapy.
Genmab announced updated results from multiple clinical trials evaluating epcoritamab-bysp, a T-cell engaging bispecific antibody, demonstrating significant efficacy in first-line treatment of diffuse large B-cell lymphoma (search) (DLBCL) and follicular lymphoma (search) (FL). The data, presented at the 67th Annual Meeting of the American Society of Hematology (ASH) in Orlando, Florida, reinforce the potential utility of fixed-duration epcoritamab therapy in earlier treatment lines.
EPCORE NHL-2 Trial Delivers Strong Response Rates
The EPCORE NHL-2 trial evaluated epcoritamab in combination with standard chemotherapy regimens across multiple arms. In Arm 8, two-year follow-up data showed that fixed-duration epcoritamab plus rituximab plus dose-attenuated cyclophosphamide, doxorubicin, vincristine, and prednisone (R-mini-CHOP) achieved an overall response rate (ORR) of 93% and complete response (CR) rate of 86% in elderly patients with newly diagnosed DLBCL ineligible for full-dose R-CHOP (n=28).
Responses demonstrated durability, with an estimated 79% of all responders maintaining their response at two years. Among the 22 patients who completed eight treatment cycles, 20 achieved CR at the end of treatment, and 90% remained in CR nearly two years later. Minimal residual disease (MRD) negativity was reported in 20 out of 21 evaluable patients, with 16 patients achieving this status by cycle 3.
"Despite an older population of newly diagnosed diffuse large B-cell lymphoma (search), the outcomes observed in Arm 8 of the EPCORE NHL-2 evaluating fixed-duration epcoritamab plus R-mini-CHOP are encouraging," said Chan Cheah, M.D., from Sir Charles Gairdner Hospital and the University of Western Australia. "These results, along with those from other arms of the trial, support the potential for combinations of epcoritamab with standard of care treatment across a range of disease settings and patient populations."
Long-Term Efficacy in High-Risk DLBCL
Arm 1 of the EPCORE NHL-2 trial demonstrated even more impressive results in patients with newly diagnosed DLBCL and high International Prognostic Index (IPI) scores. After a median follow-up of 44.2 months, treatment with fixed-duration epcoritamab plus R-CHOP resulted in an ORR of 98% and CR rate of 85% (n=47). An estimated 74% of complete responses were ongoing at three years.
High CR rates were observed regardless of IPI score, with 86% for IPI 3 versus 83% for IPI 4-5. At three years, an estimated 69% of patients remained progression-free and 83% were alive. Efficacy outcomes remained consistent across various subgroups, including age, tumor size, and cell of origin.
Follicular Lymphoma Shows Exceptional Survival
In Arm 3, patients with FL treated with fixed-duration epcoritamab plus bendamustine and rituximab (BR) demonstrated exceptional long-term outcomes. At a median follow-up of 41.3 months, three-year estimates for duration of response, duration of CR, progression-free survival, and overall survival were 87%, 87%, 83%, and 96%, respectively.
EPCORE DLBCL-3 Offers Hope for Elderly Patients
The Phase 2 EPCORE DLBCL-3 trial evaluated epcoritamab monotherapy in newly diagnosed elderly patients with DLBCL and comorbidities who were unable to receive standard anthracycline-based chemotherapy. Among 60 response-evaluable patients, the ORR was 73%, with 62% achieving a CR.
Median time to response was 1.5 months, and median time to CR was 2.1 months. An estimated 70% of all responses and 78% of CRs were ongoing at one year. In the overall population (N=66), median progression-free survival was 13.0 months, and 54% of patients were progression-free at one year, while 65% were alive.
"Elderly patients who are living with diffuse large B-cell lymphoma (search), particularly those with comorbidities, often are not able to tolerate standard treatment, creating a tremendous need for effective chemotherapy-free options," said Umberto Vitolo, M.D., from Candiolo Cancer Institute in Turin, Italy. "The study showed that treatment with fixed-duration epcoritamab as a monotherapy demonstrated encouraging results in this population that typically has poor outcomes."
Safety Profile Remains Manageable
Across all trials, the safety profile of epcoritamab remained consistent with previous studies. In the EPCORE NHL-2 Arm 8, treatment-emergent adverse events included Grade ≥3 infection in 32% of patients, occurring primarily within the first six cycles. TEAEs led to epcoritamab discontinuation in 11% of patients.
In the EPCORE DLBCL-3 trial, TEAEs occurred in 94% of patients, with cytokine release syndrome (CRS) being the most frequent at 71%. CRS events were primarily low grade, with 92% occurring in cycle 1 and 98% of cases resolving by data cutoff. Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 18% of patients, with 11 out of 12 cases resolving.
Clinical Significance and Future Directions
These results represent a significant advancement in lymphoma treatment, particularly for elderly patients and those with high-risk disease features. DLBCL is the most common type of non-Hodgkin lymphoma (search) worldwide, accounting for approximately 25-30% of all NHL cases, with approximately 25,000 new cases diagnosed annually in the U.S.
"The ongoing epcoritamab development program continues to generate positive data supporting its potential as a core therapy alone and in combination across a range of B-cell malignancies, both as an initial treatment and in later lines of therapy," said Dr. Judith Klimovsky, Executive Vice President and Chief Development Officer of Genmab.
Epcoritamab is an IgG1-bispecific antibody created using Genmab's proprietary DuoBody technology and administered subcutaneously. The therapy is designed to simultaneously bind to CD3 (search) on T cells and CD20 (search) on B cells, inducing T-cell-mediated killing of CD20+ cells. Epcoritamab has received regulatory approval under the brand names EPKINLY in the U.S. and Japan, and TEPKINLY in the EU for certain lymphoma indications.
Genmab and AbbVie (search) continue to evaluate epcoritamab across multiple ongoing Phase 3 trials, including studies in relapsed/refractory DLBCL, newly diagnosed DLBCL in combination with R-CHOP, and previously untreated FL. The safety and efficacy of epcoritamab have not been established for these investigational uses.