Genmab Announces New Data from Phase 1b/2 EPCORE® CLL-1 Highlighting Potential of Epcoritamab as Monotherapy and in Combination for Patients with Richter Transformation (RT)

Core Insights - Genmab A/S announced new data from the Phase 1b/2 EPCORE CLL-1 trial evaluating epcoritamab-bysp for treating Richter transformation (RT) in chronic lymphocytic leukemia (CLL) patients, highlighting its potential as a therapeutic option [2][11] Group 1: Epcoritamab Monotherapy (Arm 2A) - In Arm 2A, 42 patients with RT received epcoritamab monotherapy, achieving an overall response rate (ORR) of 57% in first-line settings and 38% in second- or later-line settings [3][4] - The median overall survival (OS) was 27.5 months for first-line patients, while second- or later-line patients had a median OS of 9.8 months [3] - Cytokine release syndrome (CRS) occurred in 86% of patients, with 79% experiencing Grade 1/2 events, and most CRS events resolved within a median of three days [4] Group 2: Epcoritamab and Lenalidomide Combination (Arm 2B) - In Arm 2B, 11 previously-treated RT patients received epcoritamab combined with lenalidomide, resulting in an ORR of 82% and a complete response (CR) rate of 73% [5][6] - The median progression-free survival (PFS) was 5.7 months, with median OS not reached at nine months [5] - CRS events were primarily low grade, resolving in a median of four days, with one patient discontinuing due to CRS [6] Group 3: Epcoritamab and R-CHOP Combination (Arm 2C) - In Arm 2C, 30 previously untreated RT patients received epcoritamab combined with R-CHOP, achieving an ORR of 77% and a CR rate of 63% [8][9] - The median OS was 16.4 months, and the median PFS was 16.0 months [9] - CRS events were primarily low grade, with a median resolution time of 2.0 days, and no patients discontinued due to CRS [10] Group 4: Safety Profile - Across all arms, common treatment-emergent adverse events (TEAEs) included infection (74%), anemia (50%), and thrombocytopenia (48%) in Arm 2A [12] - In Arm 2B, 100% of patients experienced CRS, with serious TEAEs occurring in 10 out of 11 patients [12] - Arm 2C reported 90% of patients experiencing Grade ≥3 TEAEs, with three treatment-related Grade 5 events [12] Group 5: Background on Richter Transformation - Richter transformation (RT) is a rare and aggressive evolution of CLL, often leading to poor prognosis with complete remission rates around 20% and median survival less than one year following standard treatments [13] Group 6: Trial Overview - The EPCORE CLL-1 trial is a global, Phase 1b/2 study assessing the safety and preliminary efficacy of epcoritamab in patients with relapsed/refractory CLL, SLL, and RT [14]