TG Therapeutics reports data from MZL cohort of Phase 2b UNITY-NHL trial
TG Therapeutics reported interim data from the ongoing single-arm marginal zone lymphoma, or MZL, cohort of its Phase 2b clinical trial known as UNITY-NHL. The MZL cohort of UNITY-NHL is designed to investigate umbralisib as a single agent in patients with relapsed or refractory MZL. Umbralisib is an investigational, oral, once daily PI3K delta inhibitor with unique inhibition of CK1 epsilon and is currently under development for the treatment of non-Hodgkin lymphoma, or NHL, and chronic lymphocytic leukemia, or CLL. The MZL cohort of UNITY-NHL enrolled patients with relapsed or refractory MZL who had received prior treatment with one or more lines of therapy including at least one anti-CD20 regimen. In August 2018, the trial completed enrollment with 69 treated patients. The interim data reported included safety and tolerability data on all 69 treated patients and efficacy data on 42 patients who were enrolled at least 9 cycles prior to the data cut-off date. The primary endpoint is overall response rate, or ORR, as assessed by IRC using criteria adopted from the International Working Group criteria for malignant lymphoma. Overall, there was 88% clinical benefit rate by IRC. All patients achieving a complete response by IRC remain on study and 86% of patients had a reduction in tumor burden The median time to initial response was 2.7 months. Interim safety data were presented for all 69 treated patients with a median duration of exposure of 6.9 months. No unexpected toxicities were observed. The most common adverse events were diarrhea, nausea and fatigue, with the majority of events grade 1 in severity. The most frequent grade 3 or higher adverse events were neutropenia, diarrhea and ALT/AST increase, observed in 13%, 10% and 10% of patients, respectively. A subgroup analysis of patients treated for greater than six cycles was also conducted to evaluate long-term incidence of key toxicities of interest occurring after six cycles of treatment. Median duration of treatment of this subgroup was 10.1 months. In this subgroup, grade 3 or higher adverse events of interest were rare, limited to two patients with diarrhea and one patient with pneumonitis, with no events of ALT/AST elevation, pneumonia or colitis.