Threshold Pharmaceuticals' Partner Merck KGaA, Darmstadt, Germany Initiates Phase 1 Dose Escalation Study of TH-302 in Combin...
March 27 2014 - 7:00AM
Marketwired
Threshold Pharmaceuticals' Partner Merck KGaA, Darmstadt, Germany
Initiates Phase 1 Dose Escalation Study of TH-302 in Combination
With Gemcitabine and Nab-paclitaxel (Abraxane(R)) in Pancreatic
Cancer
SOUTH SAN FRANCISCO, CA--(Marketwired - Mar 27, 2014) -
Threshold Pharmaceuticals, Inc. (NASDAQ: THLD) today announced that
Threshold's partner Merck KGaA, Darmstadt, Germany, through its
biopharmaceutical division, has initiated a Phase 1 dose escalation
study assessing the safety, tolerability and anti-tumor activity of
the investigational hypoxia-targeted drug TH-302 in combination
with gemcitabine and nab-paclitaxel (Abraxane®) in patients with
previously untreated, locally advanced unresectable or metastatic
pancreatic adenocarcinoma.
"Pancreatic cancer patients are in need of meaningful
therapeutic improvements and multi-drug combinations have proven to
be an effective approach in some tumor types," said Tillman Pearce,
M.D., Chief Medical Officer of Threshold. "This new dose escalation
study is evaluating an investigational triple therapy approach with
TH-302 plus gemcitabine and nab-paclitaxel, two compounds that have
been approved for the treatment of pancreatic cancer, in an effort
to continue the pursuit of developing potentially meaningful
therapeutic improvements to existing therapies in one of the most
difficult to treat cancers."
Supportive rationale for the study was derived from preclinical
animal xenograft models of pancreatic cancer, in which greater
anti-tumor activity was associated with the "triplet" combination
(TH-302 plus gemcitabine plus nab-paclitaxel) compared with that of
the "doublet" combination (gemcitabine plus nab-paclitaxel) without
apparent increases in hematological toxicity or peripheral
neuropathy.1
"The evaluation of potential new TH-302 combination therapies is
an important component of the overall development program for
TH-302 in pancreatic cancer," said Barry Selick, Ph.D., Chief
Executive Officer of Threshold. "We are pleased that Merck in
Darmstadt, Germany has initiated this additional trial designed to
evaluate an investigational triplet therapeutic regimen for
patients with pancreatic cancer while continuing to enroll the
Phase 3 MAESTRO study."
About the Phase 1 Study of TH-302 in Combination with
Gemcitabine and Nab-paclitaxel
The primary objectives of the Phase 1 trial are to evaluate the
safety and tolerability of TH-302 in combination with gemcitabine
plus nab-paclitaxel in patients with previously untreated, locally
advanced unresectable or metastatic pancreatic adenocarcinoma, to
identify potential dose-limiting toxicities and to determine the
maximum tolerated dose and the recommended Phase 2 doses. Secondary
objectives include evaluating anti-tumor activity and levels of
CA19-9, exploring the effect of the combination on tumor metabolic
activity using [18F]-fluorodeoxyglucose (FDG) PET scans and
investigating pharmacokinetics. The open-label multi-center study
is expected to enroll up to 48 patients.
About the Phase 3 MAESTRO Study of TH-302 in Combination with
Gemcitabine
MAESTRO is a randomized, placebo-controlled, international,
multi-center, double-blind Phase 3 trial of TH-302 plus gemcitabine
compared with placebo plus gemcitabine and is expected to enroll
660 patients. The primary efficacy endpoint is overall survival;
the secondary endpoints include efficacy measured by
progression-free survival, overall response rate and disease
control rate, as well as assessments of safety and tolerability,
pharmacokinetics and biomarkers. MAESTRO was initiated following a
214-patient randomized controlled Phase 2b trial of TH-302 plus
gemcitabine in which the primary endpoint of improving
progression-free survival was achieved.
About Pancreatic Cancer
It is estimated that approximately 337,000 cases of pancreatic
cancer are diagnosed worldwide every year, accounting for 2.4% of
all cancers. Pancreatic cancer is the twelfth most common cancer
worldwide. Almost 67% of cases are diagnosed in people aged 65 and
over; it is uncommon in people under the age of 45. Pancreatic
cancer has a low survival rate regardless of stage of disease, with
almost 94% of patients dying from their disease within 5 years. It
is estimated that there are around 330,000 deaths from pancreatic
cancer worldwide each year.
About TH-302
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 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 Designation for the treatment of soft
tissue sarcoma and pancreatic cancer. 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 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 its
product candidates, including TH-302, and statements regarding the
TH-302 clinical development program, including the expected
enrollment and conduct of ongoing clinical trials and the timing
thereof. 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 preclinical studies in animal models of disease may not
accurately predict the result of human clinical trials of TH-302,
and 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. Further information regarding these and other risks is
included under the heading "Risk Factors" in Threshold's Annual
Report on Form 10-K, which has been filed with the Securities and
Exchange Commission on March 6, 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.
Reference
1. Sun J et al. 2013 AACR-NCI-EORTC International Conference on
Molecular Targets and Cancer Therapeutics (Abstract #C287).
Contact Laura Hansen, Ph.D. Senior Director, Corporate
Communications Phone: 650-474-8206 E-mail:
lhansen@thresholdpharm.com
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