Multinational phase 1b-2 trial of epcoritamab monotherapy for Richter transformation

The phase 1b-2 EPCORE CLL-1 trial, at 24 centers in nine countries, evaluated the subcutaneous CD3xCD20 bispecific antibody epcoritamab as monotherapy in patients with Richter transformation (RT). Eligible patients were aged 18 years or older with histologically confirmed RT (DLBCL), an ECOG performance status 2 or better, and up to two previous lines of RT-directed therapy. Epcoritamab was administered until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed overall response rate (ORR), evaluated against a null hypothesis of 30% versus an alternative of 50%. The trial enrolled 42 patients, with a median time of CLL/SLL diagnosis to RT of 7.6 years (range 0-23.9). At a median follow-up of 22.9 months (range 0.5-39.9), 20 of 42 patients had a response (47.6%; 95% CI 32.0-83.6), which did not meet the prespecified alternative hypothesis. Overall response occurred in 12 of 21 patients in the first-line population (ORR 57.1%; 95% CI 34.0-78.2), in 8 of 21 patients in the second-line or later-line population (38.1%; 18.1-61.6), and in 8 pf 20 patients with baseline TP53 aberration and/or del(17p) alteration (40%; 19.1-63.9). CRS occurred in 36 (86%) patients with three (7%) being grade 3, ICANS in five (12%; all grade 1-2), and clinical tumor lysis syndrome in two (5%; all grade 1-2). None of three fatal adverse events were considered to be related to study treatment. The authors conclude that epcoritamab showed clinically meaningful antitumor activity in patients with RT.