On February 5, 2021, the FDA approved umbralisib (Ukoniq; TG Therapeutics), an oral kinase inhibitor, for the treatment of adults with relapsed or refractory marginal-zone lymphoma (MZL) or with relapsed or refractory follicular lymphoma (FL). Umbralisib is indicated for MZL after ≥1 CD20-directed regimens, and for FL after ≥3 lines of systemic therapy.
Umbralisib is the first dual inhibitor of PI3K-delta and CK1-epsilon to be approved by the FDA, which granted it priority review for MZL and an orphan drug designation for MZL and FL.
“MZL and FL remain incurable diseases, with limited treatment options for patients who relapse after previous therapy and no defined standard of care. With the approval of umbralisib we now have a targeted, oral, once daily option, offering a needed treatment alternative for patients,” said Nathan H. Fowler, MD, Professor of Medicine, The University of Texas M.D. Anderson Cancer Center.
This FDA approval of umbralisib was based on 2 single-arm cohorts of the open-label, multicenter UNITY clinical trial that included 69 patients with MZL and 117 patients with FL who have received several lines of previous therapy. In the study, all patients received oral umbralisib 800 mg once daily until disease progression or until unacceptable toxicity. The efficacy outcome measures were overall response rate (ORR) and duration of response (DOR).
The ORR was 49% among the patients with MZL (95% confidence interval [CI], 37-61.6), with 16% reaching a complete response; the median DOR was not reached (95% CI, 9.3-not estimable). In the patients with FL, the ORR was 43% (95% CI, 33.6-52.2) and 3% achieved a complete response; the median DOR was 11.1 months (95% CI, 8.3-16.4).
The most common (≥15%) adverse reactions with umbralisib 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 adverse reactions occurred in 18% of patients, and most often resulted from diarrhea/colitis and infection. Diarrhea/colitis and transaminase elevation were the most common reasons for dose modifications.