On December 7, 2020 TG Therapeutics, Inc. (NASDAQ: TGTX), reported two triple therapy combination data presentations (Press release, TG Therapeutics, DEC 7, 2020, View Source [SID1234572320]). The first evaluated the investigational combination of umbralisib plus ublituximab (U2) plus venetoclax in patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL); and the second evaluated the investigational combination of U2 plus TG-1701, the Company’s once daily, oral, BTK inhibitor, in patients with R/R CLL or B-cell lymphoma. Data from these trials were presented at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting and exposition. Presentation highlights are included below.

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Michael S. Weiss, the Company’s Executive Chairman and Chief Executive Officer, stated, "We are extremely pleased by the triple therapy data presented today demonstrating the potential of U2 with both venetoclax and our BTK inhibitor, TG-1701." Mr. Weiss continued, "Our mission continues to be to drive toward better outcomes for patients with B-cell malignancies by developing multi-drug combinations. We believe the data with these triple combinations highlights our approach of leveraging our portfolio and standard of care therapies to build on the U2 backbone with the goal of creating potentially best in class treatments for patients in need."

PRESENTATION HIGHLIGHTS:

Poster Presentation Title: A Phase 1/2 Study of Umbralisib, Ublituximab, and Venetoclax (U2-Ven) in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)

Regimen was administered with 3 cycles of U2 as induction in cycles 1 through 3, U2 plus venetoclax in cycles 4, 5 and 6, followed by umbralisib plus venetoclax in cycles 7 through 12 in patients with R/R CLL. Patients with centrally confirmed undetectable minimal residual disease (uMRD) in the bone marrow after cycle 12 were permitted to stop all therapy, while MRD detectable patients continued on single agent umbralisib.
43 patients have been treated as of the data cutoff with 58% of patients previously exposed to a BTK inhibitor
Among evaluable patients, ORR was 77% (30/39) after cycle 3 (U2 only), 100% (31/31) after cycle 7, and 100% (27/27) after cycle 12
Among the 27 patients who finished 12 cycles of therapy:
• 41% achieved Complete Response (CR) by iwCLL criteria
• 96% achieved undetectable MRD in the peripheral blood
• 77% achieved undetectable MRD in the bone marrow
At a median follow up of 15.6 months (n=43), only 1 patient has progressed 10 months after stopping treatment
Grade 3/4 adverse events occurring in > 5% of patients were neutropenia (21%), leukopenia (12%), infusion related reactions (7%), anemia (5%), and diarrhea (5%). No TLS events were observed during venetoclax administration, with one TLS event occurring prior to venetoclax administration.
Poster Presentation Title: Clinical Activity of TG-1701, As Monotherapy and in Combination with Ublituximab and Umbralisib (U2), in Patients with B-Cell Malignancies

A total of 102 patients with R/R CLL or b-cell lymphoma have been treated with TG-1701, with patients receiving monotherapy in the dose-escalation cohort (n=25) or in the 200 mg dose-expansion cohort (n=61), or TG-1701 in combination with U2 in the dose escalation cohort (n=16)
TG-1701 monotherapy was well tolerated and the maximum tolerated dose was not reached up through 400 mg QD
Grade 3/4 adverse events (AE) occurring in >10% of patients treated with TG-1701 monotherapy were limited and included ALT increase (12%), all of which were patients treated with 400 mg QD. At the target single-agent Phase 2 dose of 200mg (QD) (n=61), AEs of special interest included Grade 3 hypertension (1.6%), atrial fibrillation (1.6%), and no instances of major bleeding observed. Grade 3/4 AEs occurring in >10% of patients treated with U2+1701 were ALT increase (25%), AST increase (19%) and neutropenia (12%).
At a median follow up of 7 months in the 200 mg QD monotherapy expansion cohorts, preliminary overall response rates (ORR) were: 95% (19/20) in CLL, 50% (6/12) in mantle cell lymphoma (MCL), and 95% (18/19) in Waldenstrom macroglobulinemia (WM)
At a median follow up of 12 months, the 1701+U2 dose escalation (using doses of 100mg to 300 mg QD of TG-1701) resulted in 79% ORR, with 22% CR rate across patients with WM, CLL, marginal zone lymphoma (MZL), diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) (n=14)
Data presented at ASH (Free ASH Whitepaper) 2020 will be available on the Publications page of the Company’s website at View Source

CONFERENCE CALL REPLAY INFORMATION
The Company hosted a conference call on November 5, 2020, with leading investigators from the UNITY-NHL and UNITY-CLL trials to discuss the data included in the ASH (Free ASH Whitepaper) 2020 abstracts. A recording of the conference call is available for replay at View Source