On December 13, 2021 TG Therapeutics, Inc. (NASDAQ: TGTX), reported four data presentations, including three oral presentations and one poster presentation, evaluating the combination of ublituximab, the Company’s investigational anti-CD20 monoclonal antibody and UKONIQ (umbralisib), the Company’s inhibitor of PI3K-delta and CKI-epsilon, (U2), as well as U2-based triple combination therapies, including U2 plus TG’s investigational BTK inhibitor TG-1701 (Press release, TG Therapeutics, DEC 13, 2021, View Source [SID1234596946]). Data presentations occurred this past weekend during the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting and exposition. Presentation highlights are included below.

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Michael S. Weiss, Chairman and Chief Executive Officer of TG Therapeutics stated, "We are excited to have showcased four presentations this past weekend, including three oral presentations, during the live ASH (Free ASH Whitepaper) annual meeting. It was also gratifying to learn that two of our oral presentations, U2 in relapsed or refractory MZL and U2 as an add-on to Ibrutinib to create a time-limited therapy, were chosen for highlights of ASH (Free ASH Whitepaper). We believe these presentations further demonstrate the potential for U2 to enhance patient care and complement current standard of care for patients with B-cell malignancies."

PRESENTATION HIGHLIGHTS

Oral Presentation Title: The Combination of Umbralisib Plus Ublituximab Is Active in Patients with Relapsed or Refractory Marginal Zone Lymphoma (MZL): Results from the Phase 2 Global Unity-NHL Trial

A total of 72 relapsed/refractory (R/R) marginal zone lymphoma (MZL) patients were enrolled in the ublituximab plus umbralisib (U2) cohort of the UNITY-NHL.
Patients had a median of 2 prior lines of therapy (range 1 – 9), with 25% refractory to their immediate prior therapy
Overall Response Rate (ORR) by independent review committee (IRC) was 70%, with 21% complete response (CR) rate (n=71),
Median duration of response (DOR) was not reached at a median follow up of 20 months.
Grade 3/4 AEs of clinical interest included diarrhea (13%), neutropenia (18%), ALT/AST increased (15%) and non-infectious colitis (2.8%).
Oral Presentation Title: Efficacy and Safety of Umbralisib, Ublituximab (U2), and U2 Plus Bendamustine in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

A total of 226 patients were treated within the DLBCL cohort of the UNITY-NHL trial. 30 patients received umbralisib monotherapy, 66 patients received ublituximab plus umbralisib or U2, and 130 patients received U2 plus bendamustine.
IRC assessed response rates:
43% ORR and 17% CR for U2 plus bendamustine triple combination (n=130)
32% ORR and 11% CR for U2 double combination (n=66)
13% ORR and 3% CR for umbralisib monotherapy (n=30)
IRC assessed median duration of response (DOR) was 3 months for umbralisib monotherapy, 28 months for U2 combination, and 8 months for U2 plus bendamustine
Both U2 and U2 + bendamustine demonstrated a manageable safety profile. Grade 3/4 AEs of special interest occurring in the U2 group (n=66) included ALT/AST increased (12%), non-infectious colitis (2%), diarrhea (2%), neutropenia (11%) and pneumonitis (2%). Grade 3/4 AEs of special interest occurring in the U2 plus bendamustine group (n=130) included ALT/AST increased (5%), non-infectious colitis (2%), diarrhea (7%), neutropenia (27%), pneumonitis (1%) and rash (2%).
Oral Presentation Title: A Phase 2 Study Evaluating the Addition of Ublituximab and Umbralisib (U2) to Ibrutinib in Patients with Chronic Lymphocytic Leukemia (CLL): A Minimal Residual Disease (MRD)-Driven, Time-Limited Approach-Limited Approach

This study utilized an "add-on" approach, where the combination of umbralisib and ublituximab (U2) was added to therapy in patients who were on ibrutinib for greater than 6 months and had detectable minimum residual disease (MRD)
Patients who achieve undetectable MRD (uMRD) or those who completed 24 cycles of therapy with detectable MRD stop all therapy and enter a period of treatment-free observation (TFO). Patients with clinical progression during TFO are eligible for re-treatment with the U2 + ibrutinib combination.
28 patients with chronic lymphocytic leukemia (CLL) were enrolled, with 27 evaluable for efficacy. Patients were on ibrutinib for a median of 21 months (range 7-67) prior to study entry.
77% of evaluable patients achieved uMRD, with a median time to first uMRD of 7.4 months
Grade 3/4 AEs included diarrhea (4%), hypertension (7%), ALT/AST increased (4%) and COVID-19 (4%).
Poster Presentation Title: The Selective Bruton Tyrosine Kinase (BTK) Inhibitor TG-1701 As Monotherapy and in Combination with Ublituximab and Umbralisib (U2) in Patients with B-Cell Malignancies

A total of 135 patients with R/R CLL or B-cell lymphoma were included in this presentation, with patients receiving 200 mg of TG-1701 in a dose-expansion cohort (n=61), 300 mg of TG-1701 in a CLL dose-expansion cohort (n=20), TG-1701 in combination with U2 in a dose escalation cohort (TG-1701 doses ranging from 100 – 300 mg once daily and umbralisib at either 600 mg or 800mg) (n=21), and a triple combination expansion cohort of 100mg of TG-1701 plus U2 (400 mg of umbralisib) (n=33).
Efficacy Overall Response Rate (ORR) and Complete Response (CR) Outcomes:
100% ORR observed in the CLL 300 mg QD TG-1701 monotherapy expansion cohort at a median follow up of 13.8 months (n=19)
95% ORR observed in the CLL 200 mg QD TG-1701 monotherapy expansion cohort at a median follow up of 20 months (n=20)
86% ORR, including 19% CR rate, observed in the 1701+U2 dose escalation cohort (using doses of 100 mg to 300 mg QD of TG-1701) at a median follow up of 20.2 months (n=21)
83% ORR, including 6% CR rate, observed in the 1701+U2 dose expansion cohort (using 100 mg QD of TG-1701 and 400 mg QD of umbralisib) at a median follow up of 2.7 months (n=18)
Grade 3/4 AEs occurring in patients treated with 200 mg QD of TG-1701 (n=61) and 300 mg QD of TG-1701 (n=20), respectively, included neutropenia (8%, 20%), ALT increased (3%, 5%), AST increased (2%, 5%) and anemia (5%, 0%). Grade 3/4 AEs occurring in patients treated with the triple combination in the U2 plus TG-1701 expansion cohort (100 mg QD TG-1701 plus 400 mg QD of umbralisib; n=19) and U2 plus TG-1701 escalation cohort (100 mg to 300 mg QD; n=21), respectively, included neutropenia (16%, 19%), ALT increased (5%, 19%), AST increased (5%, 14%).
At the time of data cut-off, no patients had discontinued treatment due to a treatment-related adverse event across all cohorts.
The above referenced presentations are now available on the Publications page of the Company’s corporate website at View Source