Threshold Pharmaceuticals Announces Positive Phase 2b Clinical Trial Results of TH-302 in Patients With Pancreatic <THLD.O>
SOUTH SAN FRANCISCO, CA, Feb 21 (MARKET WIRE) --
Threshold Pharmaceuticals, Inc. (NASDAQ: THLD)
-- Primary endpoint of Progression Free Survival was met with hazard
ratio of 0.61 (p = 0.005).
-- The combination therapy was well tolerated with a safety profile
consistent with prior studies.
Threshold Pharmaceuticals, Inc. (NASDAQ: THLD) today announced that
its 214 patient randomized controlled Phase 2b clinical trial evaluating
the efficacy and safety of two doses of the investigational agent TH-302
in combination with gemcitabine compared to gemcitabine alone in patients
with first-line advanced pancreatic cancer achieved its primary endpoint,
with a 63% improvement in progression free survival and a safety profile
consistent with previous studies. "With the results of this trial, we are
again very encouraged that TH-302 is conferring benefit to patients with
aggressive and difficult to treat cancers," said Barry Selick, Ph.D.,
Chief Executive Officer of Threshold. "We look forward to its ongoing
development with our partner Merck KGaA in this and other indications."
Clinical Trial Design
Study TH-CR-404 is a multi-center, randomized,
controlled, dose-ranging, Phase 2b crossover clinical trial of TH-302 in
combination with gemcitabine in patients with first line advanced
pancreatic cancer. The primary endpoint of the trial is progression-free
survival. The secondary endpoints are overall response rate, overall
survival, change in CA19-9 as well as various other efficacy and safety
parameters. Tumor response was evaluated at baseline and every eight
weeks using RECIST. Patients for whom monotherapy with gemcitabine is
considered standard therapy were eligible for the trial. Patients were
randomized equally into one of three cohorts: TH-302 at a dose of 240
mg/m2 plus gemcitabine, TH-302 at a dose of 340 mg/m2 plus gemcitabine,
or gemcitabine alone. Patients who successfully completed six cycles of
treatment without evidence of significant treatment-related toxicity or
progressive disease could continue to receive treatment. If a patient
experienced cancer progression on gemcitabine alone, the patient could
cross over into one of the TH-302 plus gemcitabine cohorts. The primary
efficacy analysis was performed based upon 149 investigator-assessed PFS
events and, per protocol, pooled data from the two gemcitabine plus
TH-302 dose groups in comparison to gemcitabine alone.
Results
The
median progression-free survival (PFS) was 5.6 months for patients
treated with gemcitabine in combination with TH-302 at 240 mg/m2 and 340
mg/m2 compared to 3.6 months for patients treated with gemcitabine alone.
The PFS hazard ratio comparing the TH-302 combination to gemcitabine
alone was 0.61 (95% confidence interval: 0.43 - 0.87) which was highly
statistically significant (p = 0.005). The response rate in the
combination arms was 22% compared to 12% in the gemcitabine alone group.
Results also demonstrated greater efficacy in the higher TH-302 dose
group compared to the lower dose group.
The combination was well tolerated with a safety profile that was
consistent with our prior study of this combination regimen. As in that
study, skin and mucosal toxicities related to TH-302 were dose dependent
but not dose limiting. Further detailed information regarding the results
of this trial will be presented at a future major medical conference.
"This study provides the proof of concept demonstration that TH-302
contributes to the efficacy of a known active agent and supports the
rationale for combining TH-302, a hypoxia targeting agent, with other
approved therapies," said Stew Kroll, Senior Vice President of
Biostatistics and Clinical Operations of Threshold.
About Pancreatic Cancer
Pancreatic cancer is a malignant neoplasm of
the pancreas with current treatment options including surgery,
radiotherapy and chemotherapy. Gemcitabine as a single agent or in
combination with other treatments is the most commonly used
chemotherapeutic agent in patients with advanced pancreatic cancer. It is
estimated that approximately 279,000 cases of pancreatic cancer were
diagnosed worldwide in 2008. Pancreatic cancer is the fourth most common
cause of cancer death both in the United States and internationally. The
American Cancer Society estimates that 44,030 people were diagnosed with
pancreatic cancer in the United States in 2011, and approximately 37,660
people died from the disease.
About TH-302
TH-302 is a hypoxia-targeted drug that is thought to be
activated under tumor hypoxic conditions, a hallmark of many cancer
indications. Areas of low oxygen levels (hypoxia) within tissues 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 550 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 ongoing clinical trials with TH-302 including, but
not limited to, a Phase 3 trial of TH-302 in patients with first-line
advanced soft tissue sarcoma (STS). This randomized, multi-center Phase 3
trial will investigate the use of TH-302 plus doxorubicin compared with
doxorubicin alone. The primary efficacy endpoint is overall survival. The
study is conducted under a Special Protocol Assessment with the U.S. Food
and Drug Administration. It is being run in partnership with the Sarcoma
Alliance for Research through Collaboration (SARC) and aims to enroll 450
patients with metastatic or locally advanced unresectable STS.
In Memorium
The results of this trial are dedicated to the memory of
John G. Curd, MD, Threshold's former Chief Medical Officer who died
unexpectedly on April 20, 2011. John played a key role in the design of
this trial and deserves our recognition and thanks for his efforts on
behalf of all patients living with cancer.
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 (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 TH-302's potential uses and benefits and
current and planned clinical 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, Threshold's ability to
enroll or complete its anticipated clinical trials, the time and expense
required to conduct such clinical trials and analyze data, whether such
trials confirm results from earlier trials and preclinical studies,
potential side effects associated with TH-302, issues arising in the
regulatory or manufacturing process and the results of such clinical
trials (including product safety issues and efficacy results), and
Threshold's ability to raise additional capital to continue funding its
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 Exchange
Commission on November 3, 2011 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.
