Threshold Pharmaceuticals Announces Positive Phase 2b Clinical Trial Results of TH-302 in Patients With Pancreatic Cancer
SOUTH SAN FRANCISCO, CA--(Marketwire - Feb 21, 2012) - 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.
Contact Information
Contact:
Joel A. Fernandes
Threshold Pharmaceuticals, Inc.
650.474.8273
IR@thresholdpharm.com
Posted: February 2012
