Primary results from the large B-cell lymphoma ( LBCL ) expansion cohort in the EPCORE NHL-1 phase 2 clinical trial evaluating Epcoritamab ( DuoBody-CD3xCD20 ), an investigational subcutaneous bispecific antibody, were presented at the 27th Annual Meeting of the European Hematology Association ( EHA2022 ).
In this study, Epcoritamab has demonstrated efficacy with durable responses in patients who had previously received at least two prior lines of anti-lymphoma therapy including chimeric antigen receptor ( CAR ) T-cell therapy.
The study cohort, which has included 157 relapsed / refractory LBCL patients, previously treated with a median of three lines of prior therapy, has demonstrated an overall response rate ( ORR ) of 63% and a complete response ( CR ) rate of 39%.
Baseline characteristics included 61% of patients who were refractory to primary treatment, 20% who had prior autologous stem cell transplantation ( ASCT ), and 39% who were treated with CAR T-cell therapy ( 75% of those refractory to CAR T ).
Patients enrolled in the study who were naïve to CAR T-cell therapy achieved a 69% ORR and a 42% CR and patients who received prior CAR T-cell therapy have achieved a 54% ORR and a 34% CR.
After a median follow up of 10.7 months, the median duration of response ( mDOR ) was estimated to be 12 months, while the mDOR among patients achieving a CR was not reached, with 89% still in CR at nine months.
The safety profile of Epcoritamab was consistent with previous findings. The majority of treatment-emergent adverse effects ( TEAEs ) occurred during the first 12 weeks of treatment and resolved.
The most common TEAEs of any grade ( greater than or equal to 15% ) have included cytokine release syndrome ( CRS ) ( 49.7% ), pyrexia ( 23.6% ), fatigue ( 22.9% ), neutropenia ( 21.7% ), diarrhea ( 20.4% ), injection site reaction ( 19.7% ), nausea ( 19.7% ) and anemia ( 17.8% ).
The most common grade 3 or 4 TEAEs ( greater than or equal to 5% ) have included neutropenia ( 14.6% ), anemia ( 10.2% ), neutrophil count decrease ( 6.4% ), and thrombocytopenia ( 5.7% ).
The observed grade 3 CRS was 2.5%. No grade 4/5 CRS was observed.
EPCORE NHL-1 an open-label, multi-center safety and preliminary efficacy trial of Epcoritamab including a phase 1 first-in-human, dose escalation part; a phase 2 expansion part; and an optimization part.
The trial was designed to evaluate subcutaneous Epcoritamab in patients with relapsed, progressive or refractory CD20+ mature B-NHL, including LBCL and DLBCL, the most common subtype of LBCL.
The dose escalation findings, which determined the recommended phase 2 dose, were published in The Lancet in 2021.
In the phase 2 expansion part, additional patients are treated with Epcoritamab to further explore the safety and efficacy of Epcoritamab in three cohorts of patients with different types of relapsed / refractory B-NHLs who had limited therapeutic options.
The primary endpoint of the phase 2 expansion part was ORR as assessed by an IRC. Secondary efficacy endpoints included duration of response, complete response rate, progression-free survival, and time to response as determined by the Lugano criteria. Overall survival, time to next therapy, and rate of minimal residual disease negativity were evaluated as secondary efficacy endpoints.
Epcoritamab is an investigational IgG1-bispecific antibody created using DuoBody technology.
DuoBody-CD3 technology is designed to direct cytotoxic T cells selectively to elicit an immune response towards target cell types.
Epcoritamab is designed to simultaneously bind to CD3 on T cells and CD20 on B-cells and induces T cell mediated killing of CD20+ cells.
CD20 is expressed on B-cells and a clinically validated therapeutic target in many B-cell malignancies, including diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma and chronic lymphocytic leukemia.
Large B-cell lymphoma is a fast-growing type of non-Hodgkin's lymphoma ( NHL ) that affects B-cell lymphocytes.
There are an estimated 150,000 new LBCL cases each year globally. LBCL includes DLBCL, which is the most common type of NHL worldwide and accounts for approximately 31% of all NHL cases. ( Xagena )
Source: Abbvie, 2022