FDA Places Partial Clinical Hold on Studies Featuring Umbralisib and Ublituximab in CLL and Non-Hodgkin Lymphoma

The FDA has placed a partial clinical hold on trials using umbralisib and ublituximab as a treatment for chronic lymphocytic leukemia and non-Hodgkin lymphoma.

A partial clinical hold has been placed by the FDA on studies using umbralisib and ublituximab (U2; Ukoniq) as a treatment for patients with chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma, according to a press release from developer TG Therapeutics.1

The news was delivered at the 2022 Virtual Oncology Investor Conference. With the partial clinical hold, no new patients will be allowed to enroll on trials tailored to those with CLL and non-Hodgkin lymphoma, although those who already enrolled and are experiencing a benefit will be allowed to continue with consent. Notably, the hold is not based on new data, but on concerns that will later be presented at the Oncologics Drug Advisory Committee meeting in March or April 2022.

A biologics license application for the combination of ublituximab and umbralisib for CLL and small lymphocytic leukemia was submitted to the FDA in May 2021.2 Data from the phase 3 UNITY-CLL trial (NCT02612311) trial helped support the application.3 Findings from the study indicated that patients in the intent to treat arm who received U2 experienced a significantly improved median progression-free survival (PFS) of 31.9 months compared with 17.9 months among those treated with obinutuzumab (Gazyva) and chlorambucil (HR, 0.546; 95% CI, 0.413-0.720; P <.0001). PFS rates in the 2 arms were 60.8% and 40.4% after a median follow up of 36.7 months, respectively.

Additionally, the treatment-naive population achieved a median PFS of 38.5 months in the U2 arm compared with 26.1 months in the control arm (HR, 0.482; 95% CI, 0.316-0.736; P <.001). Patients within this population had a 2-year PFS rate of 76.6% and 52.1% in both arms, respectively. Treatment with U2 also resulted in an overall response rate of 83.3% compared with 68.7% in the control group (P <.001).

In terms of safety, the most common grade 3/4 adverse effects in the U2 and control groups, respectively, were alanine aminotransferase (8.3% vs 1.0%), elevated aspartate aminotransferase (5.3% vs 2.0%), noninfectious colitis (1.9% vs 0%), infectious colitis (0.5% vs 0.5%), pneumonitis (0.5% vs 0%), rash (2.4% vs 0.5%), and opportunistic infections (5.8% vs 1.5%).


  1. TG Therapeutics falls 30% as CEO discloses partial clinical hold on blood cancer trials. News release. TG Therapeutics. January 28, 2022. Accessed January 28, 2022. https://yhoo.it/3rWhKPL
  2. TG Therapeutics announces FDA acceptance of biologics license application for ublituximab in combination with UKONIQ® (umbralisib) as a treatment for patients with chronic lymphocytic leukemia and small lymphocytic lymphoma. News release. TG Therapeutics, Inc. May 25, 2021. Accessed January 28, 2022. https://bit.ly/34gxnGj
  3. Gribben JG, Jurczak W, Jacobs R, et al. Umbralisib plus ublituximab (U2) is superior to obinutuzumab plus chlorambucil (O+Chl) in patients with treatment naïve (TN) and relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL): results from the phase 3 Unity-CLL study. Presented at: American Society of Hematology Meeting and Exposition; December 5-8, 2020; Virtual. Abstract 543. Accessed January 28, 2021. https://bit.ly/3rXBHpq