FDA Approves Umbralisib for Marginal Zone Lymphoma, Follicular Lymphoma

The FDA has granted an accelerated approval to umbralisib for the treatment of select patients with relapsed/refractory marginal zone lymphoma (MZL) and relapsed/refractory follicular lymphoma.

The agent is specifically indicated for adult patients with relapsed/refractory MZL who have previously received at least 1 anti-CD20–based regimen; it is also approved for use in adult patients with relapsed/refractory follicular lymphoma who have previously received at least 3 lines of systemic treatment.

The regulatory decision was based on data from 2 single-arm cohorts of an open-label, multicenter, multicohort trial, UTX-TGR-205 (NCT02793583), that was conducted in a total of 69 patients with MZL who had previously received at least 1 therapy, including an anti-CD20 containing regimen, and in 117 patients with follicular lymphoma who had previously received at least 2 systemic therapies. In the trial, participants received umbralisib at a once-daily dose of 800 mg until progressive disease or intolerable toxicity.

Results showed that the agent elicited an ORR of 49% in patients with MZL (95% CI, 37.0, 61.6); 16% experienced complete responses (CRs). The median duration of response (DOR) had not yet been reached (95% CI, 9.3-not evaluable) in this subgroup.

For patients with follicular lymphoma, the ORR was slightly lower, at 43% (95% CI, 33.6-52.2), with 3% of patients achieving CRs. The median DOR was 11.1 months (95% CI, 8.3-16.4) in this subgroup.

Regarding safety, the most frequently reported toxicities with umbralisib included increased creatinine, diarrhea/colitis, fatigue, nausea, neutropenia, transaminase elevation, musculoskeletal pain, anemia, thrombocytopenia, upper-respiratory tract infection, vomiting, abdominal pain, reduced appetite, and rash.

Eighteen percent of patients reported serious toxicities, which were most commonly diarrhea/colitis and infection. Transaminase elevation and diarrhea/colitis were the most common reasons for dose modifications with the agent.

Previously, the FDA granted breakthrough therapy designations to the PI3K-delta and CK1-epsilon inhibitor for MZL and orphan drug designations for MZL and follicular lymphoma based on data from the trial.

Reference

1. FDA grants accelerated approval to umbralisib for marginal zone lymphoma and follicular lymphoma. News release. FDA. February 5, 2021. Accessed February 5, 2021. http://bit.ly/3aCBqQa.