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TG Therapeutics, Inc. Announces Presentations of Its Proprietary Combination of TG-1101 Plus TGR-1202 as Well as TGR-1202 as a Single Agent in Ongoing Phase I/Ib Dose Escalation Clinical Studies
May 31, 2015
Triple therapy cohort of the combination study to be presented separately as an oral presentation tomorrow morning,
Data from both studies (over 135 patients combined between single agent and combination studies) continues to demonstrate a favorable safety profile with a high level of activity and a significant dose-response relationship observed
85% (11 of 13) CLL/SLL patients treated at the higher doses of 1202 as a single agent and in combination with TG-1101 achieved a nodal response, with most CLL patients achieving a Partial Response per iwCLL (Hallek 2008) criteria with patients on study pending further assessment
50% (3 of 6) Overall Response Rate (ORR) in Follicular Lymphoma (FL) patients treated with the higher doses of single agent TGR-1202
41% (3 of 7) ORR in patients with Diffuse Large B-Cell Lymphoma (DLBCL) treated at the higher doses of the combination of TG-1101 and TGR-1202, and a clinical benefit rate (patients achieving stable disease or better) of 86% (6 of 7)
TGR-1202 alone and in combination with TG-1101 continues to be well-tolerated with limited Grade 3/4 events and ≤5% of the patients across both studies discontinuing for adverse events, none of which were hepatic toxicity or colitis, with over 50 patients between both studies on therapy 6+ months
The following summarizes the posters presented today:
Abstract Number 8548: Ublituximab plus TGR-1202 activity and safety profile in relapsed/refractory B-cell
Today's poster presentation includes data from 55 patients with advanced relapsed and refractory high-risk CLL and
Highlights from this poster include:
- 83% (5 of 6) of CLL/SLL patients in the "high dose" cohort achieved a partial response (CLL evaluated per iwCLL 2008 criteria)
- 64% (7 of 11) ORR in patients with FL treated at the higher doses
- 50% (4 of 8) ORR in patients with DLBCL and Richter's treated at the higher doses
- Significant dose-response relationship was observed between the high and low doses in all patients, particularly in FL and DLBCL, where a significant increase in complete response rates was observed in the higher dose group
- Combination well tolerated with only 5% of patients discontinuing due to an adverse event and 33% of patients on study for 6+ months
Overview of the data presented on TGR-1202 in combination with TG-1101 (ublituximab):
Safety and Tolerability
TG-1101 in combination with TGR-1202 (referred to as "TG-1303") has been well tolerated in the 55 patients evaluable for safety, at all dose levels up through 1200 mg micronized, the highest dose level tested to date. Day 1 infusion related reactions (IRR) have been the most frequently reported adverse event in 29% of patients, with all but 1 event being Grade 1 or 2 in severity and occurring more frequently in patients with CLL. Neutropenia was the only Grade 3/4 event reported in > 5% of patients (24%), however, the inclusion criteria in this study allowed enrollment of patients with existing baseline Grade 3 neutropenia. Of the 55 patients to date, only 3 (5%) have discontinued due to an adverse event. Notably, with respect to preliminary long-term tolerability, 18 patients (33%) have now been on TG-1101 plus TGR-1202 for 6+ months, with no reported events of colitis.
Clinical Activity
The study design evaluated sequential dosing cohorts with fixed doses of TG-1101 and escalating doses of TGR-1202 with both the original formulation and the micronized formulation, which have been classified based on exposure into "lower dose" and "higher dose" cohorts (higher dose classified as 1200 mg of the original formulation or ≥600 mg of the micronized formulation). A significant dose-response relationship was observed between the high and low doses in all 39 patients evaluable for efficacy at the time of the study cut-off, particularly in the
TGR-1202 Higher* Dose | TGR-1202 Lower** Dose | ||||||||||||
Type |
Pts (n) |
CR (n) |
PR (n) |
ORR n (%) |
SD (n) |
PD (n) |
Type |
Pts (n) |
CR (n) |
PR (n) |
ORR n (%) |
SD (n) |
PD (n) |
CLL/SLL | 6 | - | 5 | 5 (83%) | 1 | - | CLL/SLL | 7 | 1 | 3 | 4 (57%) | 3 | - |
DLBCL | 7 | 2 | 1 | 3 (43%) | 3 | 1 | DLBCL | 3 | - | - | - | 1 | 2 |
FL/MZL | 11 | 2 | 5 | 7 (64%) | 4 | - | FL/MZL | 4 | - | 1 | 1 (25%) | 3 | - |
Richter's | 1 | - | 1 | 1 (100%) | - | - | Richter's | - | - | - | - | - | - |
Overall | 25 | 4 | 12 | 16 (64%) | 8 | 1 | Overall | 14 | 1 | 4 | 5 (36%) | 7 | 2 |
*Higher Dose = 1200 original formulation and 600 or > micronized | **Lower Dose = 800 original formulation and 400 micronized |
Of the 15 patients evaluable for efficacy with FL and
As seen with TGR-1202 as a single agent, responses have been shown to improve over time, with 3 of the 5 CR's achieved at subsequent efficacy assessments.
Commenting on the combination data, Dr. Matthew Lunning,
Abstract Number 7069: "Clinical activity and safety profile of TGR-1202, a novel once daily PI3K delta inhibitor, in patients with CLL and B-cell lymphoma"
Today's poster presentation includes data from 66 patients with relapsed and refractory hematologic malignancies treated with single agent TGR-1202 at escalating doses up through 1200 mg micronized QD. Highlights from this poster include:
- 88% (14 of 16) CLL patients achieved a nodal response with 63% achieving a partial response per iwCLL (Hallek 2008) criteria
-
Significant exposure-response trend observed in both CLL and
NHL , with higher plasma TGR-1202 exposures correlating with increased responses at 800 and 1200 mg once daily micronized doses - TGR-1202 continues to be well tolerated with limited Grade 3/4 events with 44% of patients on study 6+ months and < 5% of patients discontinuing TGR-1202 due to an adverse event, differentiating TGR-1202 from other PI3K-delta inhibitors, especially with respect to hepatic toxicity and colitis
Overview of the data presented on single agent TGR-1202:
Safety and Tolerability
In the 66 patients evaluable for safety, TGR-1202 has been well-tolerated with no dose-related trends in adverse events observed and patients on study for upwards of 2+ years. Grade 3 events continue to be limited with only 3 patients ( < 5%) having discontinued study due to an adverse event, none of which were for hepatic toxicity or colitis which have been common and potentially serious and life threatening with other PI3K-delta inhibitors. Neutropenia was the only Grade 3/4 event reported in > 10% of patients (11%). Notably, with respect to preliminary long-term tolerability, 29 patients (44%) have now been on TGR-1202 for 6+ months, with some patients on TGR-1202 for 2+ years, with no reported events of colitis.
Clinical Activity
Significant clinical activity was observed in patients with CLL treated at doses ≥800 mg with 88% of CLL patients (14 of 16) achieving a nodal PR, and 10 of 16 (63%) of patients achieving a response per iwCLL (Hallek 2008) criteria. The remaining two patients exhibited nodal reductions and remain on study awaiting upcoming efficacy assessments.
In patients with
Enrollment into the study continues in the 800 mg micronized dose expansion cohort for CLL patients as well as in the 1200 mg micronized dose expansion cohort for
Dr.
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Cautionary Statement
Some of the statements included in this press release, particularly those with respect to anticipating future clinical trials, the timing of commencing or completing such trials and business prospects for TG-1101, TGR-1202, the IRAK4 inhibitor program, and the anti-PD-L1 and anti-GITR antibodies may be forward-looking statements that involve a number of risks and uncertainties. For those statements, we claim the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995. Among the factors that could cause our actual results to differ materially are the following: our ability to successfully and cost-effectively complete pre-clinical and clinical trials for TG-1101, TGR-1202, the IRAK4 inhibitor program and the anti-PD-L1 and anti-GITR antibodies; the risk that early pre-clinical and clinical results that supported our
decision to move forward with TG-1101, TGR-1202, the IRAK4 inhibitor program and the anti-PD-L1 and anti-GITR antibodies will not be reproduced in additional patients or in future studies; the risk that trends observed which underlie certain assumptions of future performance of TGR-1202 will not continue, the risk that TGR-1202 will not produce satisfactory safety and efficacy results to warrant further development following the completion of the current Phase 1 study; the risk that the data (both safety and efficacy) from future clinical trials will not coincide with the data produced from prior pre-clinical and clinical trials, particularly with respect to the incidence of colitis and liver toxicity; the risk that trials will take longer to enroll than expected; our ability to achieve the milestones we project over the next year; our ability to manage our cash in line with our
projections, and other risk factors identified from time to time in our reports filed with the
TGTX - G
CONTACT:Source:Jenna Bosco Director - Investor RelationsTG Therapeutics, Inc. Telephone: 212.554.4351 Email: ir@tgtxinc.com
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