Threshold Pharmaceuticals Initiates 440-Patient, Randomized, Double-Blind, Placebo-Controlled Trial of TH-302 in Combination ...
July 01 2014 - 7:00AM
Marketwired
Threshold Pharmaceuticals Initiates 440-Patient, Randomized,
Double-Blind, Placebo-Controlled Trial of TH-302 in Combination
With Pemetrexed in Advanced Non-Squamous Non-Small Cell Lung Cancer
SOUTH SAN FRANCISCO, CA--(Marketwired - Jul 1, 2014) - Threshold
Pharmaceuticals, Inc. (NASDAQ: THLD) today announced initiation of
a 440-patient, randomized, double-blind, placebo-controlled trial
of its investigational hypoxia-activated prodrug, TH-302, in
combination with pemetrexed in advanced non-squamous non-small cell
lung cancer (NSCLC). The international Phase 2 trial is designed to
compare the combination of TH-302 and pemetrexed versus the
combination of pemetrexed and placebo as second-line therapy in
this patient population. A TH-302 dose of 400 mg/m2 will be
utilized in combination with full-dose pemetrexed. Overall survival
is the primary endpoint; secondary endpoints include safety and
assessment of anti-tumor activity as determined by progression-free
survival and objective response rate.
"The initiation of this trial is yet another example of our
commitment, and that of our partner Merck KGaA based in Darmstadt,
Germany, to develop TH-302 for the potential treatment of a broad
range of cancers," said Barry Selick, Ph.D., Chief Executive
Officer of Threshold. "Independent studies have demonstrated the
presence of hypoxia in tumors from patients with NSCLC.1 Early
clinical research conducted by Threshold also supports further
evaluation of TH-302 in combination with pemetrexed as a potential
second-line treatment for patients with non-squamous NSCLC, many of
whom still face a poor prognosis because of limited treatment
options."
"While over the past decade the ability to detect and treat
specific mutations in NSCLC has proven beneficial to some patients
with recurrent disease who harbor those mutations, there is still a
significant need for the development of new safe and effective
medicines that improve survival outcomes," said Jonathan Goldman,
MD, Director of Clinical Trials in Thoracic Oncology, UCLA
Hematology & Oncology, and principal investigator of the
ongoing trial. "TH-302 is a hypoxia-activated prodrug that has
shown encouraging anti-tumor activity across a wide range of
cancers in investigational trials, and we are excited about
evaluating TH-302 in combination with pemetrexed as potential
second-line treatment for patients with non-squamous NSCLC."
In a completed Phase 1/2 study that evaluated TH-302 in
combination with full-dose pemetrexed in 18 patients with
relapsed/refractory non-squamous NSCLC, median progression-free
survival was 7.0 months and median overall survival was 14.9
months. Of 15 patients evaluable for response, 6 (40%) achieved a
partial response including 4 confirmed responses, 6 (40%) achieved
stable disease, and 3 (20%) had progressive disease. The most
common adverse events following combination therapy of TH-302 and
pemetrexed were fatigue, anemia, stomatitis and nausea.
About NSCLC Lung cancer is the leading cause of cancer death
worldwide claiming the lives of some 1.4 million people each year.2
There are approximately 1.6 million new cases of lung cancer
diagnosed each year.2 About 85% of lung cancers are non-small cell
lung cancer (NSCLC), and 15% are small-cell lung cancers (SCLC).3
There are several types of NSCLC, each characterized by different
types of cancer cells that grow and spread in unique ways. The two
main subdivisions are "squamous" or "non-squamous", with
non-squamous comprising 70-75%.3 The American Society for Clinical
Oncology (ASCO) guidelines recommend that first-line treatment for
NSCLC should include a platinum-containing regimen in combination
with a second therapeutic agent.4 In the second-line setting,
chemotherapy is continued until disease progression or unacceptable
toxicity.4 Historically, non-squamous NSCLC patients receiving
second-line chemotherapy show median progression-free survival of
approximately 3 to 4 months and median overall survival of
approximately 8 to 10 months.
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, statements regarding the
TH-302 clinical development program, including the expected
enrollment and conduct of ongoing clinical trials including the
above-described Phase 2 clinical trial, and statements regarding
continued collaborative activities under Threshold's collaboration
with Merck KGaA, Darmstadt, Germany. 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 and Merck KGaA, Darmstadt, Germany, 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 later trials may not confirm
the results of earlier trials; Threshold's and Merck KGaA's
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.
References
1. Zegers, CML et al. Hypoxia imaging with [18F]HX4 PET in
NSCLC patients: Defining optimal imaging parameters.
Radiotherapy and Oncology 2013;109:58-64.
2. American Cancer Society. Global Cancer Facts &
Figures (2nd edition).
http://www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc-027766.pdf.
Accessed June 30, 2014.
3. American Cancer Society. Lung Cancer (Non-Small Cell).
http://www.cancer.org/acs/groups/cid/documents/webcontent/003115-pdf.pdf.
Accessed June 30, 2014.
4. Azzoli, CG et al. American Society of Clinical Oncology
Clinical Practice Guideline Update on Chemotherapy for Stage IV
Non-Small-Cell Lung Cancer. J Clin Oncol
2009;27:6251-6266.
Contact Laura Hansen, Ph.D. Senior Director, Corporate
Communications Phone: 650-474-8206 E-mail:
lhansen@thresholdpharm.com
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