On February 5, 2021, the U.S. Food and Drug Administration (FDA) granted accelerated approval to umbralisib (Ukoniq™), a kinase inhibitor including PI3K-delta and casein kinase CK1-epsilon, for adult patients with relapsed or refractory marginal zone lymphoma (MZL) who have received at least one prior anti-CD20-based regimen and adult patients with relapsed or refractory follicular lymphoma (FL) who have received at least three prior lines of systemic therapy.

FDA Grants Accelerated Approval to Umbralisib for Marginal Zone and Follicular Lymphoma

Approval was based on two single-arm cohorts of an open-label, multicenter, multicohort trial (UTX-TGR-205; NCT02793583) of 69 patients with MZL who received at least one prior therapy, including an anti-CD20 containing regimen, and 117 patients with FL after at least two prior systemic therapies. Patients received umbralisib 800 mg orally once daily until they experienced disease progression or unacceptable toxicity.

Efficacy was based on overall response rate (ORR) and duration of response (DOR) using modified 2007 International Working Group criteria assessed by an independent review committee.

For patients with MZL, ORR was 49% (95% CI = 37.0, 61.6) with 16% achieving complete responses. Median DOR was not reached (95% CI = 9.3, not evaluated) in these patients. For patients with FL, ORR was 43% (95% CI = 33.6, 52.2) with 3% achieving complete responses. Median DOR was 11.1 months (8.3, 16.4).

The most common adverse reactions (≥ 15%), including laboratory abnormalities, were increased creatinine, diarrhea (colitis), fatigue, nausea, neutropenia, elevated transaminase, 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 and infection. Diarrhea and elevated transaminase 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 orally once daily taken with food until patients experience disease progression or unacceptable toxicity.

View full prescribing information for umbralisib.

The review used Assessment Aid, a voluntary submission from the applicant to facilitate FDA’s assessment.

FDA granted the application priority review for the MZL indication and orphan drug designation for the treatment of MZL and FL. A description of FDA expedited programs is in the Guidance for Industry—Expedited Programs for Serious Conditions—Drugs and Biologics.

The MZL and FL indications were granted accelerated approval based on ORR. Continued approval is contingent on verification and description of clinical benefit in confirmatory trials.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.  

For assistance with single-patient oncology investigational new drug applications, contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.