On December 9, 2019 TG Therapeutics, Inc. (NASDAQ: TGTX), reported the first clinical data from the Company’s once daily, oral, BTK inhibitor, TG-1701, as a single agent and as a triple therapy in combination with ublituximab (TG-1101), the Company’s novel glycoengineered anti-CD20 monoclonal antibody, and umbralisib (TGR-1202), the Company’s oral, dual inhibitor of PI3K delta and CK1 epsilon, in patients with relapsed/refractory non-Hodgkin’s lymphoma (NHL) and chronic lymphocytic leukemia (CLL) (Press release, TG Therapeutics, DEC 9, 2019, View Source [SID1234552130]). Data from this Phase I trial are being presented this evening during a poster session at the 61stAmerican Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition.

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Michael S. Weiss, Executive Chairman and Chief Executive Officer, stated, "We are highly encouraged by the first clinical data presented from our once daily, BTK inhibitor, TG-1701, which has demonstrated superior selectivity for BTK compared to ibrutinib in an in vitro whole kinome screening. The data presented today show that TG-1701 is an active BTK inhibitor as a single agent and that the combination of U2 plus TG-1701 has been generally well tolerated and active with 6 of 7 patients responding to the triple therapy at 100 mg QD, the lowest dose of TG-1701 tested. We look forward to continuing dose escalation of TG-1701 in the combination arm and identifying the optimal dose for this therapy." Mr. Weiss continued, "Our goal has always been to develop the best possible combination treatment options for patients, and we are excited to present the first data from a triple combination study in which all of the agents are being developed by TG. We believe this proprietary combination has the potential to enhance the results of BTK inhibitor therapy alone and offer patients early and deep responses with a tolerable safety profile."

Below are highlights from today’s poster presentation.

Poster Presentation: Phase 1 Study of TG-1701, a Selective Irreversible Inhibitor of Bruton’s Tyrosine Kinase (BTK), in Patients with Relapsed/Refractory B-Cell Malignancies

This presentation includes safety information from 30 patients, 21 patients treated with single agent TG-1701, and 9 patients treated with the triple combination of TG-1701 plus U2.

TG-1701, a once daily BTK inhibitor, demonstrates an encouraging safety profile to date, with clinical and pharmacodynamic activity at all dose levels evaluated
30 patients have been treated with TG-1701 at doses that ranged from 100mg to 400mg once daily for TG-1701 monotherapy; dose escalation continues in the triple combination arm
Single agent TG-1701 produced partial responses at multiple dose levels (including the lowest dose tested) across multiple B-cell diseases, including mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), Waldenström’s macroglobulinemia (WM), and small lymphocytic lymphoma (SLL)
86% (6/7) of patients treated with 100 mg TG-1701 plus U2 have achieved a response
• 4 patients with follicular lymphoma (FL): 2 Complete Responses (CR), 1 Partial Response (PR) and 1 Stable Disease (SD)
• 1 PR in marginal zone lymphoma (MZL); 1 PR in Waldenström’s macroglobulinemia (WM); and 1 PR in diffuse large B-cell lymphoma (DLBCL)
All patients treated with the triple combination of TG-1701 plus U2 remain on study
ASH Poster Presentation Details

Title: Phase 1 Study of TG-1701, a Selective Irreversible Inhibitor of Bruton’s Tyrosine Kinase (BTK), in Patients with Relapsed/Refractory B-Cell Malignancies
• Publication Number: 4001
• Session: 623. Mantle Cell, Follicular, and Other Indolent B-Cell Lymphoma—Clinical Studies: Poster III
• Date and Time: Monday, December 9, 2019; 6:00 PM – 8:00 PM ET
• Location: Orange County Convention Center, Hall B
• Presenter: Chan Cheah, MD, Sir Charles Gairdner Hospital, Hollywood Private Hospital, University of Western Australia, Blood Cancer Research Western Australia
Below recaps highlights from yesterday’s oral presentation of U2 plus venetoclax.

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

This oral presentation includes data from patients with relapsed or refractory CLL treated with the triple combination of ublituximab, umbralisib, and venetoclax. Twenty-seven patients were evaluable for safety and 23 were evaluable for efficacy. Data highlights include:

Regimen was administered with 3 cycles of U2 induction/debulking to reduce the risk of tumor lysis syndrome (TLS), followed by the combination of umbralisib and venetoclax starting in cycle 4. Patients who were bone marrow MRD negative after cycle 12 stopped all therapy.
Overall response rate (ORR) of 87% (20/23) after U2 induction period at cycle 3, prior to introduction of venetoclax, in relapsed/refractory CLL patients, including patients refractory to ibrutinib
U2 induction appeared to reduce venetoclax TLS risk, with no patients remaining as TLS high-risk following 3 cycles of U2
13 patients treated for >7 cycles and 9 patients for > 12 cycles:
• 100% ORR (13/13) after cycle 7 for the triple combination
• 100% ORR (9/9) including 44% Complete Response (CR) after cycle 12 for the combination
• 100% (9/9) of patients had undetectable minimal residual disease (MRD) (<0.01%) in peripheral blood after 12 cycles of therapy; and
• 78% (7/9) of patients who completed 12 cycles of therapy had undetectable MRD in bone marrow and have stopped therapy
No patients (n=27) have progressed to date with a median follow-up of 6.4 months
Triple combination was generally well tolerated with no events of TLS observed
An open-label, multicenter, Phase 2 study evaluating U2 plus venetoclax (ULTRA-V) in treatment naïve and previously treated CLL is now open for enrollment.

All data presented is available on the Publications page of the Company’s website at View Source