The studies are of the U2 combination Ukoniq (umbralisib) and ublituximab for chronic lymphocytic leukemia (CLL) and non-Hodgkin’s lymphoma (NHL).
Speaking at the B. Riley Securities’ 2022 Virtual Oncology Investor Conference, TG Therapeutics’ chief executive officer, Michael Weiss, reported the U.S. Food and Drug Administration had placed a partial clinical hold on some of its clinical studies. No new patients can be enrolled in the specified studies, but people who are seeing benefit in them can continue with their consent.
The studies are of the U2 combination Ukoniq (umbralisib) and ublituximab for chronic lymphocytic leukemia (CLL) and non-Hodgkin’s lymphoma (NHL). The hold, according to Weiss, isn’t based on new data, but over previous concerns that the company expects to be addressed at the FDA’s Oncologic Drugs Advisory Committee meeting held in March or April.
Weiss also indicated the company is planning to submit overall survival analyses from a Phase III trial of the U2 combination in CLL comparing it to Genentech’s Gazyva (obinutuzumab) and chemotherapy chlorambucil.
Ukoniq has received accelerated approval from the FDA for treatment of adults with relapsed/refractory marginal zone lymphoma who have received at least one previous anti-CD20-based regimen and for relapsed/refractory follicular lymphoma patients who have received at least three previous systemic therapies.
Ukoniq is the first and only oral inhibitor of phosphoinositide 3 kinase (PI3K) delta and casein kinase 1 (CK1) epsilon. PI3K-delta plays a key role in cell proliferation and survival, cell differentiation, intercellular trafficking and immunity. It is expressed in both normal and malignant B cells. CK1-epsilon regulates oncoprotein translation and is associated with the pathogenesis of cancer cells, including lymphoid cancers.
Ublituximab is an investigational glycoengineered monoclonal antibody targeting a unique epitope on CD20-expression B cells. In addition to NHL and CLL, ublituximab is being evaluated in relapsing forms of multiple sclerosis.
The company has Biologics License Application (BLA)/supplemental New Drug Application (sNDA) for the U2 combination in adults with CLL and small lymphocytic lymphoma (SLL) under review by the FDA. The PDUFA date is March 25, 2022, but TG Therapeutics stated that due to the question of when the agency will hold an advisory committee meeting, they do not think it likely the FDA will hit the target action date.
On December 14, 2021, the company presented data from the Phase III UNITY-CLL trial of U2 in patients with both treatment naïve and relapsed or refractory CLL. The data were presented at the American Society of Hematology annual meeting. In the first presentation, U2 was evaluated in 210 CLL patients, including 119 who were treatment naïve (TN) and 91 who were previously treated. Two-year progression-free survival (PFS) in the treatment naïve population was 76.6% with PFS of 38.5 months; the overall response rate (ORR) in the TN population was 84%.
The second presentation was on U2 patients with co-morbidities or concomitant medications (conmed) in the Unity-CLL study. Of the participants, 131 U2 treated patients had at least one comorbidity or conmed that had the potential of creating problems with BTKi therapy. In the patients with at least one comorbidity or conmed, there was an 88% ORR compared to 83% ORR, including 5% CR, for the entire U2 population. No difference in PFS was observed in the comorbid/conmed group compared to the entire population.
At the time, Weiss stated, “We believe these presentations showcase the versatility of the U2 combination both by treatment subgroup, and also interestingly in a patient population generally characterized as unsuitable for BTKi-based therapy. While significant advances have been made in the treatment of CLL, there still remains underserved patients who may not be good candidates for or fail to respond to currently available treatments.”
