TG Therapeutics, Inc.
TGTX, an innovative, clinical-stage biopharmaceutical company today
announced clinical results from its ongoing Phase I single agent study of
TG-1101 (ublituximab), the Company's novel glycoengineered anti-CD20
monoclonal antibody and from its ongoing first-in-human Phase I single agent
study of TGR-1202, the Company's oral, once-daily, PI3K delta inhibitor. Data
from these Phase I studies are being presented today at poster sessions during
the 50^th American Society of Clinical Oncology (ASCO) Annual Meeting in
Chicago, IL, with both posters selected for discussion later in the day during
oral Poster Highlight sessions.
Today's poster presentations include data from 35 patients with rituximab
relapsed and refractory hematologic malignancies treated with TG-1101 at doses
ranging from 450 mg to 1200 mg, and from 40 patients with relapsed and
refractory hematologic malignancies treated with TGR-1202 at doses ranging
from 50 mg to 1800 mg QD.
Overview of the data presented on TG-1101:
Safety and Tolerability
TG-1101 (ublituximab) was well tolerated at all dose levels tested in 35
patients evaluable for safety, with Day 1 infusion related reactions (IRR)
being the most frequently reported adverse event. All IRR's were Grade 1 or 2
in severity, were manageable and occurred more frequently in patients with
CLL. Infusion times for the fourth and later infusions of TG-1101 averaged
approximately 90 minutes.
Clinical Activity
The overall response rate (ORR) for the Phase 1 dose escalation component and
expansion cohort was 43% (30% PR, 13% CR) among the 30 rituximab
relapsed/refractory patients evaluable for efficacy. TG-1101 displayed marked
clinical activity as a single agent in a variety of lymphoma subtypes,
reporting a 67% (4/6) response rate in patients with CLL and 44% (8/18)
response rate in iNHL (22% CR, 22% PR). A breakdown of response by lymphoma
subtype is below:
Lymphoma Type Pts CR PR ORR
(n) n (%) n (%) n (%)
CLL 6 -- 4 (67) 4 (67)
iNHL 18 4 (22) 4 (22) 8 (44)
aNHL 6 -- 1 (17) 1 (17)
Total 30 4 (13) 9 (30) 13 (43)
Among patients with CLL, depletion of circulating lymphocytes was rapid and
profound with 100% of patients achieving a peripheral response (defined as
either a normalization in absolute lymphocyte count (ALC) or > 50% reduction
in ALC from baseline) with a median time to peripheral response of 1 Day and a
median reduction in ALC at the first response assessment in excess of 90%.
A graph accompanying this release is available at
http://media.globenewswire.com/cache/8790/file/26740.pdf
Responses have been durable, with a median progression free survival (PFS)
among patients who achieved SD or better not yet reached, and a median PFS for
all patients on study of 34 weeks (n=30). A number of patients in SD or better
have continued on TG-1101 maintenance therapy, with improved responses
observed over time with continued treatment.
Commenting on the Phase I data, Dr. Owen A. O'Connor, Director of Lymphoid
Malignancies, Professor of Medicine and Experimental Therapeutics at Columbia
Medical Center, New York Presbyterian Medical Center in NY, and Study Chair
for the Phase I trial stated: "I am very impressed with the activity we've
seen to date with ublituximab, especially as a single agent anti-CD20
monoclonal antibody in patients with heavily pre-treated disease, relapsed and
in some cases refractory to prior rituximab. Ublituximab has been very well
tolerated and convenient to administer to patients with a safety profile that
lends itself to combination therapy."
Overview of the data presented on TGR-1202:
Safety and Tolerability
TGR-1202 has been well-tolerated with no dose-related trends in adverse events
observed and no MTD reached to date. Grade 3 events continue to be
limited. Notably, of the 40 patients evaluable for safety, no drug related
transaminase elevations or events of colitis have been observed, with several
patients on daily TGR-1202 for over 1 year.
Clinical Activity
Clinical activity was observed in patients with CLL treated at doses ≥ 800 mg
with all (9/9) patients exhibiting significant nodal reductions. Seven of nine
evaluable patients (78%) exhibited a nodal response ( > 50% reduction in nodal
size) of which three of these patients achieved a partial response per the
IWCLL 2008 criteria. The remaining two patients exhibited > 40% reductions in
nodal size at first efficacy assessment and remain on study awaiting upcoming
efficacy assessments.
Among all disease types, 26 patients had been treated at doses ≥ 800 mg and
were evaluable for efficacy (including patients who started at lower doses and
were escalated), with 20/26 (77%) achieving a reduction in nodal size with
TGR-1202. In addition to CLL, responses were observed in patients with
follicular lymphoma (1 PR of 2 evaluable patients started at ≥ 800 mg) and
Hodgkin's lymphoma (1 PR of 4 evaluable patients started at ≥ 800 mg).
Enrollment into the study continues as dose escalation of a recently
introduced micronized formulation of TGR-1202 dosed in a fed state is ongoing.
We project these modifications will provide exposures 3-4 fold greater than
those seen with equivalent doses of the previous formulation of TGR-1202 dosed
in a fasting state.
Dr. Howard A. Burris, the Principal Investigator for the study and Chief
Medical Officer of the Sarah Cannon Research Institute in Nashville, TN
stated, "We have been very pleased with the promising activity of TGR-1202,
especially coupled with its once per day dosing and the well-tolerated safety
profile demonstrated to date. The absence of liver related toxicity and
colitis is particularly encouraging. We are excited to continue to escalate
the dose of TGR-1202 to build upon the substantial single agent activity
demonstrated thus far."
Michael S. Weiss, the Company's Executive Chairman and Interim CEO commented
on the data, "Our goal since inception has been to develop novel drug
combinations for the treatment of B-cell malignancies that offer patients
better outcomes without the harsh side effects of traditional
chemotherapy. Collectively, today's data bring us much closer to accomplishing
our goal. Specifically, we believe we have unequivocally confirmed a
high-level of single agent activity for each of these agents with data
supportive of combining them safely, ideally for even greater
activity. Individually, we believe each of TG-1101 and TGR-1202 exhibit
best-in-class attributes setting up for what could be a best-in-class
combination. We have been aggressively enrolling into our combination clinical
trials, and look forward to sharing preliminary data from these combination
studies in the coming weeks and months as we continue to target initiation of
one or more registration studies before the end of this year."
Presentation details are as follows:
Title: A phase I trial of ublituximab (TG-1101), a novel glycoengineered
anti-CD20 monoclonal antibody in B-cell non-Hodgkin lymphoma patients with
prior exposure to rituximab.
* Abstract Number: 8524
* Presentation Date & Time: Friday, May 30, 2014, 1:00 PM - 4:00 PM CT
* Poster Display: Room S405, Poster Board #4
* Presenter: Owen A. O'Connor, MD, PhD, Columbia University Medical
Center, New York, NY
* Discussion Session: 4:30 – 5:45 PM CT; Room S406
* Link to Poster: www.tgtherapeutics.com/ASCO2014-Poster-8524.pdf
Title: Activity of TGR-1202, a novel once-daily PI3K delta inhibitor, in
patients with relapsed or refractory hematologic malignancies.
* Abstract Number: 2513
* Presentation Date & Time: Friday, May 30, 2014, 1:00 PM - 4:00 PM CT
* Poster Display: Room E354b, Poster Board #27
* Presenter: Howard A. Burris, MD, Sarah Cannon Research
Institute, Nashville, TN
* Discussion Session: 4:30 – 5:45 PM CT; E Arie Crown Theater
* Link to Poster: www.tgtherapeutics.com/ASCO2014-Poster-2513.pdf
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