FDA Grants Fast Track Designation to Ublituximab Plus Umbralisib in Chronic Lymphocytic Leukemia

The FDA has granted a Fast Track designation to the combination of ublituximab (TGTX-1101) plus umbralisib (TGR-1202; U2) for the treatment of adult patients with chronic lymphocytic leukemia (CLL), TG Therapeutics announced in a press release.

"We are extremely pleased to have received Fast Track designation for the ublituximab plus umbralisib regimen, or the U2 combination, to treat adult patients with CLL,” said Michael S. Weiss, executive chairman and chief executive officer, TG Therapeutics, in a statement. “The application for Fast Track was based on data from the UNITY-CLL Phase 3 study that we announced earlier this year had met its primary endpoint of progression-free survival (PFS).”

The company announced plans to present the data from this trial, supporting the designation, later in 2020.

The global, controlled phase 3 UNITY-CLL trial (NCT02612311) randomized patients to receive 1 of 4 treatment arms, including the U2 combination, ublituximab single agent, umbralisib single agent, or obinutuzumab plus chlorambucil as the active control arm. Enrollment was completed in October 2017, which included a total of 420 patients enrolled to the 2 combination arms.

Overall, 60% of the patients included in the study had treatment-naïve CLL, and 40% had relapsed/refractory disease. The primary end point was PFS, and the secondary end point was overall response rate.

According to topline results presented earlier this year, the U2 doublet improved PFS compared with obinutuzumab and chlorambucil in both patients with untreated and relapsed/refractory CLL, and this improvement, assessed by an Independent Review Committee, was statistically significant (P <.0001). The study was stopped early due to superior efficacy.

To be included in the trial, patients had to have an ECOG performance status of 0 to 2, but they were excluded if they had any major surgery, chemotherapy, or immunotherapy within the last 21 days. They also were excluded if they had evidence of hepatitis B virus, hepatitis C virus, or a known HIV infection; a stem cell transplant within 3 months of study entry; transformation of CLL to aggressive non-Hodgkin lymphoma; or prior therapy with obinutuzumab and/or chlorambucil, or a PI3K delta inhibitor.

UNITY-CLL is being conducted under a Special Protocol Assessment agreement with the FDA.

“This designation holds several important advantages to potentially expedite the development and regulatory review of U2 and underscores the significant unmet medical need that still exists for patients with CLL,” Weiss stated. “We look forward to presenting data from the UNITY-CLL Phase 3 trial later this year, which we plan to use as the basis of a U2 regulatory submission for CLL.”

Ublituximab is a glycoengineered monoclonal antibody targeting a specific and unique epitope on the CD20 antigen, which is found on mature B-lymphocytes. Umbralisib is an oral once-daily dual inhibitor of both the PI3K-delta and CK1-epsilon. This agent is currently under review by the FDA for a potential accelerated approval for the treatment of patients with previously treated marginal zone lymphoma who received at least 1 prior anti-CD20-based regimen or follicular lymphoma following at least 2 prior lines of systemic therapy.

TG Therapeutics has completed enrollment for a phase 3 clinical trial evaluating U2 as treatment of patients with treatment-naïve or relapsed/refractory CLL, and 2 additional phase 3 studies, evaluating ublituximab single agent in patients with relapsing forms of multiple sclerosis, have also completed enrollment.

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_{TG Therapeutics Announces Fast Track Designation Granted by the FDA to Ublituximab in Combination with Umbralisib for the Treatment of Adult Patients with Chronic Lymphocytic Leukemia. News Release. TG Therapeutics. October 21, 2020. Accessed October 21, 2020. https://bit.ly/34iciwc}