Duvelisib (Copiktra): A Comprehensive Monograph on a Dual PI3K-δ/γ Inhibitor for Hematologic Malignancies

I. Executive Summary

Duvelisib, marketed under the brand name Copiktra, is a first-in-class, orally administered small molecule that functions as a dual inhibitor of the delta (δ) and gamma (γ) isoforms of phosphoinositide 3-kinase (PI3K).[1] It is approved for the treatment of adult patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have received at least two prior lines of systemic therapy.[4] CLL and SLL are considered manifestations of the same disease, differing primarily in the location of the malignant cells, which are found predominantly in the bloodstream and bone marrow in CLL and in the lymph nodes in SLL.[2]

The regulatory approval of duvelisib for CLL/SLL was primarily based on the results of the pivotal Phase 3 DUO trial, a randomized study that compared duvelisib to the anti-CD20 monoclonal antibody ofatumumab.[6] In the indicated patient population of heavily pretreated individuals, duvelisib demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS), the study's primary endpoint.[8] This efficacy established duvelisib as a viable therapeutic option for a patient population with limited alternatives.