The FDA ( Food and Drug Administration ) has granted accelerated approval to Ukoniq ( Umbralisib ), a kinase inhibitor including PI3K-delta and casein kinase CK1-epsilon, for the following indications:
a) adult patients with relapsed or refractory marginal zone lymphoma ( MZL ) who have received at least one prior anti-CD20-based regimen;
b) adult patients with relapsed or refractory follicular lymphoma ( FL ) who have received at least three prior lines of systemic therapy.
Approval was based on two single-arm cohorts of an open-label, multi-center, multi-cohort trial, UTX-TGR-205, in 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 2 prior systemic therapies.
Patients received Umbralisib 800 mg orally once daily until 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 marginal zone lymphoma, the ORR was 49% ( 95% CI: 37.0, 61.6 ) with 16% achieving complete responses.
Median DOR was not reached ( 95% CI: 9.3, NE ) in these patients.
For patients with follicular lymphoma, the 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 ( more than 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 recommended Umbralisib dose is 800 mg taken orally once daily with food until disease progression or unacceptable toxicity. ( Xagena )
Source: FDA, 2021