Threshold Announces Data From Ongoing Phase 1/2 Trial of TH-302
Plus Bevacizumab (Avastin(R)) in Patients With Recurrent
Glioblastoma
CHICAGO, IL--(Marketwired - May 30, 2014) - Threshold
Pharmaceuticals, Inc. (NASDAQ: THLD)
- Objective response rate of 24% (one complete response
and three partial responses) in patients with recurrent
glioblastoma following progression on single-agent
bevacizumab
- Median progression-free survival of 3.1 months on
combination therapy vs. 2.4 months on prior single-agent
bevacizumab
- Enrollment at 670 mg/m2 TH-302 in
combination with bevacizumab is ongoing
Threshold Pharmaceuticals, Inc. (NASDAQ: THLD) today announced
new clinical data from an ongoing investigator-sponsored Phase 1/2
trial of its investigational hypoxia-activated prodrug, TH-302, in
combination with bevacizumab (Avastin®) in patients with recurrent
glioblastoma following progression on single-agent bevacizumab. The
results are being presented today as part of the poster highlights
session on Central Nervous System Tumors at the 50th Annual Meeting
of the American Society of Clinical Oncology (ASCO) in Chicago
[Abstract #2029 (Poster #20)]. The data will also be discussed at
Threshold's Analyst Event to be held Sunday, June 1, 2014, at 6:00
PM Central Time in Chicago and accompanied by a live webcast.
"Effective treatments for patients with recurrent glioblastoma
who become refractory to bevacizumab are clearly needed," said
Andrew J. Brenner, M.D., Ph.D., Principal Investigator of the study
and Clinical Investigator with the Institute for Drug Development
at the Cancer Therapy & Research Center at The University of
Texas Health Science Center at San Antonio, Texas. "In the limited
number of patients treated, it is notable that some patients
experienced objective tumor shrinkage with TH-302 plus bevacizumab,
particularly given that objective responses are rarely seen at this
advanced stage of the disease. Moreover, median progression-free
survival with TH-302 plus bevacizumab was longer than with prior
single-agent bevacizumab. Based on these early signals of clinical
activity, we are continuing evaluation of TH-302 in this extremely
challenging-to-treat population of patients with glioblastoma. Our
next steps are to further investigate the 670 mg/m2 TH-302 dose
given with bi-weekly bevacizumab in a multi-center study in this
bevacizumab-refractory patient population."
The objectives of the ongoing Phase 1/2 investigator-sponsored
trial include evaluating the safety and tolerability of TH-302,
determining the dose-limiting toxicities and the maximum-tolerated
dose of TH-302, and assessing preliminary signals of clinical
activity in patients with bevacizumab-refractory recurrent
glioblastoma. The ASCO poster reports on a total of 17 patients
treated with bevacizumab 10 mg/kg every two weeks and TH-302 dose
escalated 240-670 mg/m2 every two weeks (four-week cycle) until
disease progression. Patients had received a median of three prior
systemic anticancer regimens including both chemoradiation and
bevacizumab.
Key findings to be reported at ASCO are as follows:
Preliminary assessment of safety and tolerability
No Grade 4 adverse events were observed at any dose. Three Grade
3 adverse events were observed: skin ulceration at 340 mg/m2, oral
mucositis at 670 mg/m2, and thrombocytopenia at 670 mg/m2. The
primary TH-302 related toxicities were mucosal: rectal/anal
mucositis in one of four patients at 480 mg/m2 (Grade 2) and six of
seven patients at 670 mg/m2 (all Grade 1 or 2). Limited oral
mucositis was observed.
Preliminary assessment of clinical activity
In 17 patients evaluable for response according to Response
Assessment in Neuro-Oncology (RANO) criteria, best responses
included one complete response (1CR) and three partial responses
(3PR) for a response rate of 24%, and eight stable disease (8 SD)
assessments for a clinical benefit rate of 65%; five patients had
progressive disease (5 PD). The longest disease stabilization is
ongoing at 30 months.
The median progression-free survival (PFS) for patients treated
with TH-302 plus bevacizumab was 3.1 months, while these patients
experienced PFS of 2.4 months on their first bevacizumab regimen.
The 4-month PFS rate was 26%. Median overall survival of patients
treated with TH-302 plus bevacizumab was 4.9 months.
Poster Details
The poster titled, "Phase 1/2 study of investigational
hypoxia-targeted drug, TH-302, and bevacizumab in recurrent
glioblastoma following bevacizumab failure" [Abstract #2029 (Poster
#20)] is being presented at the Poster Highlights Session on
Central Nervous System Tumors from 1:00 PM - 4:00 PM Central Time,
Friday, May 30, 2014, in Room E354b, to be followed by a Discussion
from 4:30 PM - 5:45 PM in Room E450.
Analyst Event with Clinical Experts on Sunday, June 1, 2014
Threshold will host an evening event for investors and analysts
on Sunday, June 1, 2014, at 6:00 PM Central Time at the Four
Seasons Hotel Chicago (120 East Delaware Place, Walton Room). The
event will include presentations highlighting TH-302 data presented
at ASCO. Guest speakers scheduled to give presentations include Dr.
Paul G. Richardson, Clinical Program Leader, Director of Clinical
Research, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer
Institute, R.J. Corman Professor of Medicine, Harvard Medical
School, Boston, Massachusetts, and Dr. Andrew J. Brenner, Clinical
Investigator with the Institute for Drug Development at the Cancer
Therapy & Research Center at The University of Texas Health
Science Center at San Antonio, Texas. RSVP to
lhansen@thresholdpharm.com.
The event is open to investors and analysts. Threshold invites
the public and the media to listen to the presentations via the
live webcast, which will be available under Webcasts in the
Investors section of www.thresholdpharm.com or can be accessed
using the following link:
http://psav.adobeconnect.com/thresholdpharmaceuticals/. The
presentations are scheduled to begin at approximately 6:15 PM
Central Time. A replay of the presentations will be archived on the
site for 30 days.
About Glioblastoma and Hypoxia
Glioblastoma is the most common and most aggressive of the
primary malignant brain tumors in adults (also known as Grade IV
astrocytoma). Median survival is approximately 15 months; the
five-year survival rate is approximately 3%. There are an estimated
30,000 new cases of glioblastoma per annum in the U.S. and
Europe.
Hypoxia, a predominant characteristic of glioblastoma and most
solid tumors, is associated with tumor growth, progression and
resistance to conventional radiation and chemotherapies, as well as
poor patient survival. Bevacizumab is a biologic antibody designed
to interfere with the tumor blood supply by directly binding to a
protein called VEGF. Preclinical data suggest that antiangiogenic
agents, such as bevacizumab, may increase tumor hypoxia, which
supports the rationale for combination therapy with a
hypoxia-targeted agent in glioblastoma.
About TH-302
TH-302 is an investigational hypoxia-activated prodrug that is
designed to be activated under tumor hypoxic conditions, a hallmark
of many cancers. Areas of low oxygen levels (hypoxia) in solid
tumors are due to insufficient blood supply as a result of aberrant
vasculature. Similarly, the bone marrow of patients with
hematological malignancies has also been shown, in some cases, to
be severely hypoxic.
TH-302 is currently under evaluation in two Phase 3 trials: one
in combination with doxorubicin versus doxorubicin alone in
patients with soft tissue sarcoma, and the other in combination
with gemcitabine versus gemcitabine and placebo in patients with
advanced pancreatic cancer (MAESTRO). Both Phase 3 trials are being
conducted under Special Protocol Agreements with the U.S. Food and
Drug Administration (FDA). The FDA and the European Commission have
granted TH-302 Orphan Drug Designations for the treatment of soft
tissue sarcoma and pancreatic cancer. TH-302 is also being
investigated in earlier-stage clinical trials of other solid tumors
and hematological malignancies, in combination with chemotherapy
and antiangiogenic therapy, and for certain cancers, is being
investigated as a monotherapy.
Threshold has a global license and co-development agreement for
TH-302 with Merck KGaA, Darmstadt, Germany, which includes an
option for Threshold to co-commercialize in the U.S.
About Threshold Pharmaceuticals
Threshold Pharmaceuticals, Inc. is a biotechnology company
focused on the discovery and development of drugs targeting tumor
hypoxia, the low oxygen condition found in microenvironments of
most solid tumors as well as the bone marrows of some hematologic
malignancies. This approach offers broad potential to treat a
variety of cancers. By selectively targeting tumor cells, we are
building a pipeline of drugs that hold promise to be more effective
and less toxic to healthy tissues than conventional anticancer
drugs. For additional information, please visit our website
(www.thresholdpharm.com).
Forward-Looking Statements
Except for statements of historical fact, the statements in this
press release are forward-looking statements, including statements
regarding the potential therapeutic uses and benefits of TH-302 and
statements regarding the expected completion and enrollment of
current and potential future trials of TH-302. These statements
involve risks and uncertainties that can cause actual results to
differ materially from those in such forward-looking statements.
Potential risks and uncertainties include, but are not limited to:
the ability of Threshold, Merck KGaA, Darmstadt, Germany, and
third-party investigators to enroll or complete TH-302 clinical
trials; the time and expense required to conduct such clinical
trials and analyze data; issues arising in the regulatory or
manufacturing process and the results of such clinical trials
(including product safety issues and efficacy results); the risk
that the final data from ongoing trials may be materially different
from the preliminary data that Threshold or third-party
investigators have reported; the risk that later trials may not
confirm the results of earlier trials; Threshold's and Merck KGaA's
(Darmstadt, Germany) dependence on single source suppliers,
including the risk that these single source suppliers may be unable
to meet clinical supply demands for TH-302 which could
significantly delay the development of TH-302; risks related to
Threshold's dependence on its collaborative relationship with Merck
KGaA, Darmstadt, Germany, including its dependence on decisions by
Merck KGaA, Darmstadt, Germany regarding the amount and timing of
resource expenditures for the development of TH-302; and
Threshold's need for and the availability of resources to develop
TH-302 and to support Threshold's operations. Further information
regarding these and other risks is included under the heading "Risk
Factors" in Threshold's Quarterly Report on Form 10-Q, which has
been filed with the Securities and Exchange Commission on May 1,
2014 and is available from the SEC's website (www.sec.gov) and on
our website (www.thresholdpharm.com) under the heading "Investors."
We undertake no duty to update any forward-looking statement made
in this news release.
Contact Laura Hansen, Ph.D. Senior Director, Corporate
Communications Phone: 650-703-6523 E-mail:
lhansen@thresholdpharm.com
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