Threshold Pharmaceuticals Initiates Phase 2 Study of TH-302 in Patients With
SOUTH SAN FRANCISCO, CA -- (Marketwired) -- 08/08/13 -- Threshold
Pharmaceuticals, Inc. (NASDAQ: THLD) today announced the initiation
of a Phase 2 clinical trial to evaluate the efficacy and safety of
TH-302, its investigational hypoxia-targeted drug, in patients with
melanoma. The study will also investigate a range of biomarkers
including serum, tumor biopsy, and PET imaging hypoxia biomarkers
that may predict treatment outcomes and be associated with tumor
response to TH-302 therapy. Threshold's partner for the development
of TH-302, Merck KGaA, Darmstadt, Germany, will fund 70% of
development costs associated with this study.
Tumor hypoxia, or regions of low-oxygen, is a hallmark of many solid
tumors and is associated with poor prognosis. Cells in the hypoxic
regions exhibit an increased potential for invasiveness, metastasis,
and treatment resistance. Furthermore, hypoxia may also suppress the
immune response to cancer.
"Hypoxia is believed to be an important therapeutic target for
patients with metastatic melanoma," said Principal Investigator
Anthony Joshua, a medical oncologist at the Princess Margaret Cancer
Centre and also Assistant Professor at University of Toronto.
"Targeting hypoxic melanoma cells may help in slowing tumor
progression and treatment resistance and has the potential to be an
adjunct to current therapies. We are excited to initiate this study."
In a previous Phase 1 trial, responses were observed in patients with
advanced melanoma treated with TH-302. Out of 34 patients, seven
patients (21%) achieved a partial response including patients with
BRAF mutant and wild-type tumors, and 12 patients (35%) achieved
stable disease yielding a clinical benefit rate of 56%. Median
progression-free survival was 3.5 months.
"We are excited to collaborate with world class researchers in the
field of tumor hypoxia at the University of Toronto," said Tillman
Pearce, M.D., Chief Medical Officer of Threshold. "This Phase 2 study
holds strategic importance for the overall TH-302 development program
in potentially broadening therapeutic applications for TH-302 as well
as facilitating potentially important biomarker research."
About the Phase 2 Study
The Phase 2 trial is a single-arm,
multi-center study investigating the clinical efficacy and safety of
TH-302 administered at 480 mg/m2 weekly on a 28-day cycle (three
weeks on, one week off) in up to 40 patients with advanced melanoma.
The primary endpoint is three-month progression-free survival.
Secondary endpoints include response rate, duration of response,
overall survival, safety and evaluation of potential imaging, serum,
and tissue biomarkers that may be associated with tumor response and
predict for efficacy and safety of TH-302 therapy.
The American Cancer Society estimates there will be
76,690 new cases of melanoma and 9,480 deaths in the U.S. in 2013.
The five-year survival rate for metastatic melanoma ranges from 5% to
10% with a median survival of less than eight months with treatment.
The introduction of immunotherapies in recent years as well as BRAF
and MEK inhibitors has had a significant impact of the treatment of
patients with advanced melanoma, yet new therapies are still needed.
TH-302 is an investigational hypoxia-targeted drug 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
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 (STS), 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 Designation for the treatment of STS.
TH-302 is also being investigated in hematological malignancies and
in combination with other therapies in a variety of solid tumors.
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 the
microenvironments of most solid tumors as well as the bone marrows of
some patients with 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).
Except for statements of historical fact,
the statements in this press release are forward-looking statements,
including statements regarding the timing and potential results of
the Phase 2 trial of TH-302 in patients with advanced melanoma, and
potential therapeutic uses and benefits of TH-302 to treat patients
with soft tissue sarcoma, pancreatic cancer or other cancers. 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 to enroll or complete anticipated clinical
trials, the time and expense required to conduct such clinical trials
and analyze data, whether later trials confirm the results of earlier
trials, whether the Phase 3 trial data is sufficient to support
regulatory approval to market TH-302, and 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 1, 2013 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.
Laura Hansen, Ph.D.
Senior Director, Corporate Communications
Press spacebar to pause and continue. Press esc to stop.