On June 4, 2019 TG Therapeutics, Inc. (NASDAQ: TGTX) reported positive interim data from the ongoing single-arm marginal zone lymphoma (MZL) cohort of its Phase 2b UNITY-NHL trial currently evaluating umbralisib as a single agent in patients with relapsed/refractory MZL (Press release, TG Therapeutics, JUN 4, 2019, View Source [SID1234536894]). 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 (NHL) and chronic lymphocytic leukemia (CLL).
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The interim data were presented today in an oral session during the 55th American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. The slides presented are available on the Company’s corporate website at www.tgtherapeutics.com/publications.cfm.
Summary of Data Presented:
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 (safety population) and efficacy data on 42 patients who were enrolled at least 9 cycles (28 day cycles) prior to the data cut-off date (interim efficacy population). The primary endpoint is overall response rate (ORR) as assessed by IRC using criteria adopted from the International Working Group for malignant lymphoma.
Efficacy
Analysis of the interim efficacy population (n=42) with a median follow-up of 12.5 months showed the following:
Interim Efficacy Population (n=42)
Overall Response Rate by IRC (CR + PR), % 52%
Complete Response by IRC (CR), (%) 19%
Partial Response by IRC (PR), (%) 33%
Median duration of response, months NR (95% CI: 8.4 – NE)
CI = confidence interval; NR = not reached; NE = not estimable; SD = stable disease
Additional Efficacy Highlights:
52% ORR, with 17% CR, by IRC assessment for patients who had received 2 or more prior lines of therapy, n=23
88% clinical benefit rate by IRC, n=42, (defined as patients obtaining Complete Response + Partial Response + Stable Disease)
All patients achieving a Complete Response by IRC remain on study (range: 10.1+ to 15.7+ months)
Median time to initial response was 2.7 months
Kaplan-Meier (KM) estimate of progression-free survival (PFS) at 12 months was 66%, with the median PFS not reached
Safety
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.
Key Safety Findings (n=69):
No events of colitis were reported and only 1 event of Grade 3 pneumonitis was reported
Grade 3 infections were limited, occurring in 3 patients (bronchitis, pneumonia, and influenza)
Discontinuations due to umbralisib-related AEs were limited (14%) with no discontinuations after 6 months due to a treatment-related AE
No deaths occurred on study
ABOUT THE UNITY-NHL PHASE 2b STUDY—Marginal Zone Lymphoma Cohort
The multicenter, open-label, UNITY-NHL Phase 2b study – Marginal Zone Lymphoma cohort was designed to evaluate the safety and efficacy of single agent umbralisib, in patients with MZL who have received at least one prior anti-CD20 regimen. The primary endpoint is overall response rate (ORR) as determined by central Independent Review Committee (IRC) assessment.
The MZL cohort completed enrollment in August 2018 with a total of 69 patients enrolled and receiving at least one dose of umbralisib. In February of 2019, the Company announced that the MZL cohort met its primary endpoint of ORR as determined by central IRC for all treated patients (n=69). While the study has already met the Company’s target guidance of 40-50% ORR, the final analysis of ORR will be conducted when all treated patients have had at least 9 cycles (cycle = 28 days) of follow-up. Secondary endpoints include safety, duration of response, and progression-free survival (PFS).
ABOUT BREAKTHROUGH THERAPY DESIGNATION
The Company announced in January of 2019 that the U. S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation for umbralisib for the treatment of adult patients with marginal zone lymphoma who have received at least one prior anti-CD20 regimen.
The FDA’s Breakthrough Therapy designation is intended to expedite the development and review of a drug candidate that is planned to treat a serious or life-threatening disease or condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement on one or more clinically significant endpoints over available therapies.