On February 5, the U.S. Food and Drug Administration granted accelerated approval to umbralisib (Ukoniq), a kinase inhibitor including PI3K-delta and CK1-epsilon, for the following indications:
Approval was based on two single-arm cohorts of an open-label, multicenter, multicohort trial, UTX-TGR-205. They included 69 patients with marginal zone lymphoma who received at least one prior therapy, including an anti–CD20-containing regimen, and in 117 patients with follicular lymphoma after at least two prior systemic therapies.
Patients received umbralisib at 800 mg orally once daily until disease progression or unacceptable toxicity. Efficacy was based on overall response and duration of response using modified 2007 International Working Group criteria assessed by an independent review committee.
For patients with marginal zone lymphoma, the overall response rate was 49% (95% confidence interval [CI] = 37.0%–61.6%), with 16% achieving complete responses. Median duration of response was not reached (95% CI = 9.3–not evaluable) in these patients.
For patients with follicular lymphoma, the overall response rate was 43% (95% CI = 33.6%–52.2%) with 3% achieving complete responses. Median duration of response was 11.1 months (8.3–16.4).
The most common (> 15%) adverse reactions, 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 adverse reactions occurred in 18% of patients, most often from diarrhea-colitis and infection. Diarrhea-colitis and transaminase elevation were the most common reasons for dose modifications.
The prescribing information provides warnings and precautions for adverse reactions including infections, neutropenia, diarrhea and noninfectious colitis, hepatotoxicity, and severe cutaneous reactions.
The recommended umbralisib dose is 800 mg taken orally once daily with food until disease progression or unacceptable toxicity.