On December 06, 2015 TG Therapeutics, Inc. (Nasdaq:TGTX), reported updated clinical results from its ongoing Phase I proprietary combination study of TG-1101 (ublituximab), the Company’s novel, glycoengineered monoclonal antibody and TGR-1202, the Company’s oral, once-daily, PI3K delta inhibitor as well as data from the Phase I study of TGR-1202 in combination with obinutuzumab plus chlorambucil (Press release, TG Therapeutics, DEC 6, 2015, View Source [SID:1234508445]). Data from these Phase I studies were presented this weekend at poster sessions during the 57th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition being held at the Orange County Convention Center in Orlando, FL.

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Michael S. Weiss, the Company’s Executive Chairman and Interim CEO commented on the data, "We and our clinical investigators continue to be impressed with the activity and safety profile of our proprietary TG-1303 regimen with almost all CLL patients responding and over 70% of heavily pre-treated patients with indolent lymphoma responding to 1303. We are also very excited by the data in patients with large cell lymphoma where we are seeing 35% response rates in heavily pre-treated patients. Collectively, we believe these data support advanced clinical studies for TG-1303 across CLL and NHL and, accordingly, we plan to expand our UNITY clinical program into NHL in 2016. Finally, we are excited to see the high level of activity of a TGR-1202 based regimen in front-line CLL. We believe the safety and efficacy profile observed in those front-line patients sets the stage for what we should expect to see from TG-1303 in front-line patients included in our UNITY-CLL Phase 3 trial, which should open for enrollment in the coming weeks." Mr. Weiss continued, "We appreciate the strong support of our clinical investigators and thank them and their patients for participating in these important clinical trials."

Dr. Matthew Lunning, Assistant Professor, Division of Hematology at the University of Nebraska Medical Center and lead author for the poster presentation stated, "The principal goal for any novel-novel combination study is to establish safety and combinability of two agents. With the combination of ublituximab and TGR-1202, patients were not only able to achieve high response rates and durable remissions, but most importantly, were able to stay on treatment with limited discontinuations due to adverse events, which has been commonly seen with other novel targeted agents in this class. Many of the patients enrolled onto this study have been heavily pre-treated with limited treatment options, especially patients with DLBCL, and the ability to offer patients a novel-novel combination which has the potential to extend and improve patient lives is of great excitement."

The following summarizes the posters presented this weekend:

Ublituximab + TGR-1202 Demonstrates Activity and Favorable Safety Profile in Relapsed/Refractory B-Cell NHL and High-Risk CLL: Phase I Results (Abstract Number 1538)

This poster was presented yesterday, Saturday December 5th during the ASH (Free ASH Whitepaper) Annual Meeting and included data from patients with relapsed and refractory NHL and high-risk CLL treated with the combination of TG-1101 (ublituximab) and TGR-1202. The combination has been well tolerated in the 71 patients evaluable for safety at all dose levels up through 1200mg micronized. This was a heavily pretreated population with high-risk features, including 58% refractory to last treatment with multiple previous lines of rituximab based therapy. Efficacy data was presented on patients treated at the higher doses of TGR-1202 (1200mg of the original formulation and 600mg or greater of the micronized formulation).

Highlights from this poster include:

80% (8 of 10) ORR in patients with CLL/SLL, including 1 CR and 7 PRs
Remaining 2 patients had stable disease, one of which remains on study and the other, an ibrutinib refractory patient, progressed after 2 cycles

75% of CLL patients had high-risk cytogenetics (17p and/or 11q del)
Data supports the current Phase 3 UNITY-CLL Study of TG-1101 + TGR-1202 in CLL

71% (12 of 17) ORR in heavily pretreated patients with indolent NHL (FL & MZL), including 4 CRs (24%) and 8 PRs, with 4 of the remaining 5 patients achieving stable disease

35% (6 of 17) ORR in patients with DLBCL and Richter’s Transformation, 3 of which achieved a CR, with 2 additional patients achieving stable disease

94% of DLBCL patients were refractory to prior therapy with 69% of patients rituximab refractory, including one patient with triple hit lymphoma

Of the 16 DLBCL patients, 9 were GCB subtype, 3 were ABC subtype, and 4 patients’ subtype was unknown, with notable activity (ORR and PFS) observed in patients with confirmed GCB subtype

Combination of 1303 was well tolerated, with only 8% of patients discontinuing due to an adverse event:
Notably, the only Grade 3/4 adverse event occurring in > 5% of patients was neutropenia. Of the 71 patients available for safety, only 6 patients (8%) discontinued due to a TGR-1202 related event

Twenty-six patients have been on the combination of TG-1101 plus TGR-1202 for 6+ months, with no events of colitis reported to date

Safety profile supports multi-drug regimens
A Phase I Trial of TGR-1202, a Next Generation Once Daily PI3K-Delta Inhibitor in Combination with Obinutuzumab Plus Chlorambucil, in Patients with Chronic Lymphocytic Leukemia (Abstract Number 2942)

The poster was presented today, Sunday December 6th during the ASH (Free ASH Whitepaper) Annual Meeting and includes data from patients with treatment naïve and previously treated CLL treated with TGR-1202 in combination with the glycoengineered anti-CD20 mAb, obinutuzumab, and chlorambucil. The study design evaluated escalating doses of TGR-1202 which was dosed orally once-daily starting at Day 1 of Cycle 1. Obinutuzumab and chlorambucil were administered according to their FDA labeled dosing regimen. The combination was dosed in 18 patients, of which 15 were treatment naïve and 3 were previously treated. All patients were evaluable for safety and efficacy.

Highlights from this poster include:

100% (15 of 15) ORR in treatment naïve CLL patients, with 33% of patients achieving a CR, and 47% of patients achieving MRD negativity

95% (17 of 18) ORR in treatment naïve and relapsed/refractory CLL patients, with 28% of patients achieving a CR
Remaining patient achieved a 45% nodal reduction and remains on study, progression-free

Notably, all previously treated CLL patients were refractory to a prior BTK inhibitor and had at least one high-risk cytogenetic abnormality

The combination demonstrated acceptable tolerability, which notably differed from that observed when TGR-1202 was combined with TG-1101 in patients with relapsed or refractory CLL, specifically regarding neutropenia (78% vs. 30%), thrombocytopenia (78% vs. < 10%), and transaminase elevations (39% vs. 8%)

The median PFS has not been reached, with the longest patient on study now 20+ months on TGR-1202 daily maintenance at 800mg

POSTER Presentation details

A copy of the poster presentations are available on the Company’s website at www.tgtherapeutics.com, located on the Publications Page, within the Pipeline section.