Phase 2 epcoritamab CD3×CD20 consolidation seeks deeper remissions after at least 6 months of BTK inhibition in high-risk CLL

This Phase 2, single-arm, open-label UC Irvine study evaluates epcoritamab consolidation in chronic lymphocytic leukemia with residual disease while receiving a Bruton tyrosine kinase inhibitor (BTKi). Epcoritamab, developed by Genmab and AbbVie, binds CD20 on malignant B cells and CD3 on T cells to redirect immune killing. Participants must have received a BTKi for at least 6 months and still have CLL detectable by flow cytometry, with protocol limits on circulating lymphocytes and lymph-node size.

High-risk eligibility includes at least one treatment line before the current BTKi, del(17p)/TP53 abnormalities, or complex karyotype. The study evaluates deeper remission, including measurable residual disease, and safety in this consolidation setting. Modern CLL care includes covalent BTK inhibitors and venetoclax-based therapy, while pirtobrutinib is FDA-approved after prior covalent BTKi treatment without a universal requirement for previous venetoclax. This trial asks whether adding a CD3×CD20 engager can deepen a controlled but incomplete BTKi response, rather than treating all patients with overt BTKi progression.