FDA accelerated approval of umbralisib for R/R MZL and R/R FL

On February 5, 2021, it was announced that the U.S. Food and Drug Administration (FDA) approved umbralisib, a phosphoinositide 3 kinase-δ (PI3K-δ) and casein kinase 1-ε (CK1-ε) inhibitor, for the treatment of adults with relapsed or refractory (R/R) marginal zone lymphoma (MZL) who have received ≥ 1 prior anti-CD20 based regimen, and for adults with R/R follicular lymphoma (FL) who have received ≥ 3 prior lines of therapy.¹ This accelerated approval was based on results from the phase II UNITY-NHL trial (NCT02793583), which have now been published by Nathan Fowler in the Journal of Clinical Oncology.²  Umbralisib was previously granted priority review for the MZL indication.

Umbralisib^1,3

• An oral, once daily, inhibitor of PI3K-δ (which is highly expressed in hematopoietic cells and malignant lymphoid diseases) and CK1-ε (which drives growth and survival of lymphoma cells by regulating oncoprotein translation).
• Previously granted breakthrough therapy designation for the treatment of MZL and orphan drug designation for the treatment of MZL and FL.
• Currently being evaluated in combination with other agents for patients with non-Hodgkin lymphoma and chronic lymphocytic leukemia.

UNITY-NHL trial (NCT02793583)^1,4

• A phase IIb randomized, open-label, multicenter, multicohort study assessing the efficacy and safety of umbralisib alone, and the combination of ublituximab + umbralisib with or without bendamustine, in patients with previously treated non-Hodgkin lymphoma.
• Dosage of umbralisib: 800 mg once daily.
• Primary endpoint: overall response rate.
• Secondary endpoint: progression-free survival.

Results¹

• The efficacy of umbralisib as monotherapy was assessed in two cohorts, those with MZL (n = 69) and those with FL (n = 117).
  • The overall response rate was 49% and 43%, respectively.
  • A complete response was seen in 16% and 3.4% of patients, respectively.
  • Median duration of response was not yet reached for the MZL cohort and was 11.1 months for the FL cohort.
• The safety of umbralisib was assessed from a pooled population of 221 patients with MZL and FL in three single arm, open-label trials, and one open-label extension trial.
  • Serious adverse events occurred in 18% of patients; those that occurred in ≥ 2% of patients were diarrhea-colitis (4%), pneumonia (3%), sepsis (2%), and urinary tract infection (2%).
  • The most common adverse events (> 15%) were increased creatinine (79%), diarrhea‑colitis (58%, 2%), fatigue (41%), nausea (38%), neutropenia (33%), ALT increase (33%), AST increase (32%), musculoskeletal pain (27%), anemia (27%), thrombocytopenia (26%), upper respiratory tract infection (21%), vomiting (21%), abdominal pain (19%), decreased appetite (19%), and rash (18%).