On September 23, 2019 TG Therapeutics, Inc. (NASDAQ: TGTX), reported that data from two Phase 1/2 trials were presented at the XVIII International Workshop on Chronic Lymphocytic Leukemia (iwCLL), currently being held in Edinburgh, Scotland (Press release, TG Therapeutics, SEP 23, 2019, View Source [SID1234539695]). These data were previously presented earlier this year at the 15th International Conference on Malignant Lymphoma (ICML), held in Lugano, Switzerland. Highlights from the presentations are included below.

Presentation Title: A Phase 2 Study to Assess the Safety and Efficacy of Umbralisib in Patients with Chronic Lymphocytic Leukemia (CLL) Who Are Intolerant to Prior BTK or PI3K Delta Inhibitor Therapy

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This presentation includes data from patients with CLL who are intolerant to prior BTK or PI3K delta inhibitor therapy who were then treated with single agent umbralisib. To be eligible for the study patients had to have received prior treatment with a BTK inhibitor or a PI3K delta inhibitor and discontinued therapy due to intolerance and were in need of subsequent therapy. Fifty-one patients were evaluable for safety of which 50 were evaluable for Progression Free Survival (PFS).

Data highlights include:

Umbralisib demonstrated a favorable safety profile in patients intolerant to prior BTK (ibrutinib or acalabrutinib) or PI3K delta (idelalisib) therapy

Only 12% discontinued due to an umbralisib adverse event, of which only one patient discontinued due to a recurrent adverse event (AE) previously experienced with prior kinase inhibitor therapy (ibrutinib)

In this previously treated CLL population, 67% had a high-risk molecular / genetic marker and 6% had an ibrutinib resistance mutation, the estimated median progression free survival (PFS) was 23.5 months and overall survival (OS) not reached at a median follow-up of 15.7 months

As of the cut-off date, 58% of patients have been on umbralisib for a duration longer than their prior BTK or PI3k inhibitor

Presentation Title: Phase I/II Triple Therapy Study of Umbralisib and Ublituximab (U2) Combined with Checkpoint Inhibition in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL) and Richter’s Transformation (RT)

This presentation includes data from patients with relapsed or refractory CLL or RT treated with the triple combination of ublituximab, umbralisib, and pembrolizumab. Patients with CLL received 2 cycles of the U2 regimen before pembrolizumab was added for an additional 4 cycles, followed by umbralisib maintenance. Patients with RT received U2 + pembrolizumab for the first 4 cycles, followed by U2 maintenance. Twenty patients were evaluable for safety (11 CLL patients and 9 RT patients) and 19 were evaluable for efficacy (11 CLL and 8 RT).

Data highlights include:

The triple combination was well tolerated, with immune mediated toxicities not appearing above what would be expected with either umbralisib or pembrolizumab alone

In this heavily pre-treated cohort with a median of 2 (1-9) prior lines of therapy:

91% (10 of 11) Overall Response Rate (ORR) in patients with relapsed/refractory CLL

83% (5 of 6) ORR in BTK refractory CLL patients, with 4 of 5 responders achieving a response to U2 alone at the patient’s first efficacy assessment, prior to the addition of pembrolizumab

38% (3 of 8) ORR in RT, with two durable complete responses; 1 subject relapsed post-CAR-T in CR for 12 months and 1 subject progressed post-transplant continuing on study in CR now 20+ months. Two additional subjects were in stable disease, one with a 49% reduction in tumor burden.

The data presentations are now available on the Publications page, located within the Pipeline section, of the Company’s website at www.tgtherapeutics.com/publications.cfm.