AbbVie to present results from two clinical trials of epcoritamab

AbbVie (ABBV) announced new results from two ongoing clinical trials evaluating epcoritamab, a CD3xCD20 bispecific T-cell-engaging antibody administered subcutaneously, in adult patients with diffuse large B-cell lymphoma at the 66th Annual Meeting and Exposition of the American Society of Hematology. Arm 1 of the Phase 1b/2 EPCORE NHL-2 multi-arm trial evaluates fixed-duration investigational epcoritamab in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone in untreated high-risk DLBCL patients with International Prognostic Index scores of 3 to 5. Results from this arm of the study showed an overall response rate of 100% and a complete response rate of 87%. Among complete responders, an estimated 83% remained in remission after two years. Separately, three-year follow-up results from the Phase 2 EPCORE NHL-1 trial evaluating epcoritamab monotherapy in challenging-to-treat adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy showed that among the 41% of patients who achieved a CR, an estimated 52% were still responding at three years. EPCORE NHL-2 Results in First-Line DLBCL: The EPCORE NHL-2 trial enrolled 46 evaluable patients considered to have high-risk DLBCL, identified by International Prognostic Index scores of 3 to 5, a range associated with poor long-term outcomes. The IPI is a key tool used by oncologists to predict the prognosis of aggressive B-cell lymphomas.9 At screening, 35% of patients had bulky disease, and 21% had double-hit/triple-hit DLBCL, which are aggressive subtypes caused by major genetic mutations. A minimal residual disease analysis from blood samples showed that 91% of patients achieved MRD negativity, indicating no detectable disease as defined by ctDNA. The most common treatment-emergent adverse events were neutropenia, anemia, cytokine release syndrome, fatigue, nausea, pyrexia, and injection-site reaction. Four patients discontinued epcoritamab due to TEAEs; fatal TEAEs occurred in two patients. CRS events were mostly low grade and mainly occurred after the first full dose. All CRS cases resolved, and none led to discontinuation. Immune effector cell-associated neurotoxicity syndrome occurred in two patients and resolved in a median of 2.5 days without leading to discontinuation. EPCORE NHL-1 Results in Third-Line LBCL: Three-year follow-up results from the Phase 2 EPCORE NHL-1 trial evaluated epcoritamab monotherapy in 157 patients with R/R LBCL after two or more lines of prior therapy and showed that epcoritamab continues to deliver durable responses in challenging-to-treat patients. Additional data results include: The ORR was 59%, and CR was 41%. Median duration of response was 20.8 months and median duration of CR was 36.1 month. A MRD analysis from blood sample showed that 45.4% of patients achieved MRD negativity, as defined by ctDNA. The most common TEAEs were CRS, fatigue, and pyrexia; CRS rates remained unchanged since prior reports. Fatal TEAEs were reported in 20 patients; 10 patients had Grade 5 COVID-19. 73% of patients who received epcoritamab for two or more years did not experience a Grade 3 or higher infection after two years. Incidence of Grade 3 or higher cytopenias was highest during the first eight weeks of treatment and rates were within 0-13% in subsequent 12-week time periods up to week 144. Immunoglobulin G levels decreased by a median of ~20% after the start of epcoritamab treatment and remained stable over time.