Threshold Pharmaceuticals Announces Preliminary Data From Phase 1/2
Study of TH-302 in Combination With Bevacizumab in Patients With
VIENNA, AUSTRIA -- (Marketwire) -- 09/30/12 -- Threshold
Pharmaceuticals, Inc. (NASDAQ: THLD) today announced preliminary data
from an ongoing dose-escalation Phase 1/2 clinical trial of its
investigational hypoxia-targeted drug TH-302 in combination with
bevacizumab in patients with recurrent glioblastoma. No dose-limiting
toxicity has been reported to date in the first two dose cohorts (240
mg/m2 TH-302 plus bevacizumab and 340 mg/m2 TH-302 plus bevacizumab);
dose escalation is ongoing. Preliminary results in six patients show
a median time to progression (worsening of disease) of 128 days
compared with a median time to progression of 89.5 days these same
patients experienced while taking single-agent bevacizumab prior to
study enrollment. The results were presented in a poster at the
European Society for Medical Oncology (ESMO) 2012 Congress taking
place September 28 - October 2, 2012, in Vienna, Austria (Abstract
"These very early data from a small number of patients are providing
first insight into potential combination of TH-302 with bevacizumab
in treating patients with recurrent glioblastoma," 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 and Research Center in San Antonio, Texas. "Safe and
effective treatment options for this particularly aggressive cancer
are urgently needed, and we look forward to further evaluation of
TH-302 as dose escalation in this study continues."
Glioblastoma remains an incurable malignancy with poor survival
despite aggressive surgery and chemoradiation therapy. When
glioblastoma recurs, a standard salvage therapy is bevacizumab, 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 combining TH-302 -- a
drug designed to target and kill cells in hypoxic regions of the
tumor -- with bevacizumab in treating glioblastoma.
The study is enrolling patients with recurrent glioblastoma whose
disease has progressed following initial treatment with bevacizumab
and who are scheduled for debulking craniotomy (brain surgery to
remove tumor tissue). Patients are randomized to treatment with a
single dose of TH-302 (575 mg/m2) or placebo prior to surgery,
followed by postoperative combination therapy of bevacizumab (10
mg/m2 every two weeks) and TH-302 dose-escalated 240-480 mg/m2 every
2 weeks (4 week cycle) until disease progression.
No dose limiting toxicity has been reported to date. There were no
Grade 3 or 4 adverse events observed with 240 mg/m2 TH-302. One Grade
3 adverse event (skin ulceration) and no Grade 4 adverse events have
been observed thus far in the second cohort at 340 mg/m2 TH-302. Data
from the first six patients treated with TH-302 plus bevacizumab in
the first two dose cohorts were presented at the ESMO 2012 Congress.
Examination of surgical specimens revealed extensive areas of
hypoxia. Five patients had stable disease including one patient with
a target lesion best response by Response Assessment in
Neuro-Oncology (RANO) criteria. One patient had progressive disease.
"We are pleased with these first data from combining TH-302 with
bevacizumab to treat patients with glioblastoma," said Barry Selick,
Ph.D., Chief Executive Officer of Threshold. "We believe TH-302 has
the potential to be complementary to targeted cancer therapies, and
we will continue to evaluate its safety and efficacy in combination
with a variety of antiangiogenic agents in different tumor types."
TH-302 is a hypoxia-targeted drug designed to be
activated under tumor hypoxic conditions, a hallmark of many cancers.
Areas of low oxygen levels (hypoxia) are common in many solid tumors
due to insufficient blood vessel growth. Similarly, the bone marrow
of patients with hematological malignancies has also been shown, in
some cases, to be extremely hypoxic.
TH-302 has been investigated in over 700 patients in Phase 1/2
clinical trials to date in a broad spectrum of tumor types, both as a
monotherapy and in combination with chemotherapy treatments and other
targeted cancer drugs. Threshold has several additional ongoing
clinical trials, the most advanced of which is a Phase 3 pivotal
study evaluating TH-302 in combination with doxorubicin versus
doxorubicin alone in patients with soft tissue sarcoma. In February
2012, Threshold signed a global license and co-development agreement
for TH-302 with Merck KGaA, Darmstadt, Germany.
About Threshold Pharmaceuticals
Threshold 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
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 to treat patients with cancer. 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,
Threshold's ability to enroll or complete its anticipated 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). 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 August 6, 2012 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
Laura Hansen, Ph.D.
Senior Director, Corporate Communications
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