On February 5, 2021, the FDA granted accelerated approval to umbralisib (Ukoniq; TG Therapeutics), a dual inhibitor of PI3Kδ and CK1ε, for adult patients with relapsed or refractory marginal zone lymphoma (MZL) who have received ≥1 previous anti-CD20–based regimens, and adult patients with relapsed or refractory follicular lymphoma who have received ≥3 previous lines of systemic therapy.
The FDA previously granted orphan drug designation to umbralisib for both indications, and priority review for the MZL indication.
The approval of umbralisib was based on data from 2 single-arm cohorts of an open-label, multicenter, clinical trial, UTX-TGR-205, which included 69 patients with MZL who had received ≥1 previous therapies and 117 patients with follicular lymphoma who had received ≥2 previous systemic therapies. The main efficacy outcomes measures included ORR and duration of response (DOR).
In the MZL subgroup, the ORR was 49%, with 16% achieving complete response. Median DOR was not reached. In the follicular lymphoma subgroup, the ORR was 43%, with 3% achieving complete response. Median DOR was 11.1 months.
The most common (>15%) AEs, including laboratory abnormalities, were increased creatinine, diarrhea-colitis, fatigue, nausea, neutropenia, transaminase elevation, musculoskeletal pain, anemia, thrombocytopenia, upper respiratory tract infection, vomiting, abdominal pain, decreased appetite, and rash. Serious AEs occurred in 18% of patients, most often from diarrhea-colitis and infection.