Threshold Announces Data From Ongoing Phase 1/2 Trial of TH-302
Plus Dexamethasone in Patients With Relapsed/Refractory Multiple
Myeloma
CHICAGO, IL--(Marketwired - May 30, 2014) - Threshold
Pharmaceuticals, Inc. (NASDAQ: THLD)
- Preliminary clinical benefit rate of 31% (three partial
responses and two minimal responses) in patients treated at the
maximum-tolerated dose of TH-302 and low-dose
dexamethasone
- Objective responses observed in heavily pretreated patients
including prior treatment with proteasome inhibitors [including
carfilzomib (Kyprolis®)] and IMiDs [including
pomalidomide (Pomalyst®)]
- Enrollment completed at the previously established TH-302
maximum-tolerated dose (340 mg/m2)
- Combination regimen of TH-302 and proteasome inhibitor
bortezomib (Velcade®) to be investigated in final
stage of ongoing trial
Threshold Pharmaceuticals, Inc. (NASDAQ: THLD) today announced
new preliminary clinical data from an ongoing company-sponsored
Phase 1/2 trial of its investigational hypoxia-activated prodrug,
TH-302, in combination with low-dose dexamethasone in patients with
relapsed/refractory multiple myeloma, a cancer of the bone marrow.
The results are being presented today as part of the poster
highlights session on Lymphoma and Plasma Cell Disorders at the
50th Annual Meeting of the American Society of Clinical Oncology
(ASCO) in Chicago [Abstract #8534 (Poster #14)]. The data will also
be discussed by clinical experts at Threshold's Analyst Event to be
held Sunday, June 1, 2014, at 6:00 PM Central Time in Chicago and
accompanied by a live webcast.
"Effective treatments for patients with advanced multiple
myeloma who become refractory to current standards of care with
proteasome inhibitors or immunomodulatory drugs (IMiDs) remains an
area of exquisite unmet medical need," said Paul Richardson, M.D.,
Clinical Program Leader, Director of Clinical Research, Jerome
Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, R.J.
Corman Professor of Medicine, Harvard Medical School, Boston,
Massachusetts. "The presence of hypoxia in the diseased bone marrow
may present a new therapeutic target for treating multiple myeloma
and underlies the rationale for evaluating hypoxia-targeted agents
in this disease. In the limited number of patients treated, it is
noteworthy that objective responses were observed in this heavily
pretreated patient population, including patients who received
prior therapy with a proteasome inhibitor (including carfilzomib)
and an immunomodulatory agent (including pomalidomide), which are
typically used in advanced and later stage multiple myeloma
patients. Based on these early signals of clinical activity, we are
looking forward to initiating the final stage of the ongoing trial
in which patients will receive TH-302 and bortezomib, a combination
that demonstrated synergistic activity in preclinical models of
multiple myeloma."
The objectives of the ongoing Phase 1/2 trial include
determining the safety and tolerability of TH-302 and
dexamethasone, the dose-limiting toxicities and the
maximum-tolerated dose of TH-302, and assessing preliminary signals
of clinical activity in patients with relapsed/refractory multiple
myeloma. The dose of TH-302 administered in the dose escalation
portion of the study was 240, 340, or 480 mg/m2 (depending on the
dose cohort into which a patient enrolled) given on days 1, 4, 8,
and 11 of a 21-day cycle, with 40 mg dexamethasone given on the
same days as TH-302. Previously, the maximum tolerated dose was
reported to be 340 mg/m2 TH-302.1
Enrollment of patients with relapsed/refractory multiple myeloma
in the dose-escalation and dose-expansion portions of the study is
now complete, including 24 patients enrolled at the maximum
tolerated dose of TH-302 (340 mg/m2). Patients had received a
median of 6.5 systemic therapies prior to enrollment. The ASCO
presentation includes data from 24 patients in the dose-escalation
and dose-expansion portions of the study who initiated treatment
prior to March 1, 2014; analyses reflect the clinical database as
of May 19, 2014. Of these 24 patients, 17 were treated at the
maximum tolerated dose of TH-302.
Key findings to be reported at ASCO are as follows:
Preliminary assessment of safety and tolerability
The most common adverse events related to TH-302 occurring in at
least 25% of patients were nausea and fatigue. The most common
Grade 3/4 hematologic adverse events related to TH-302 were
thrombocytopenia (29%) and leukopenia (25%). Dose-limiting
toxicities of Grade 3 stomatitis were reported during the first
treatment cycle for the first two patients treated at 480 mg/m2
TH-302; therefore, the maximum tolerated dose of TH-302 was
established at 340 mg/m2.
Preliminary assessment of clinical activity
Of the 24 patients included in the ASCO presentation, 23 were
evaluable for response. According to modified International Myeloma
Working Group (IMWG) criteria, best responses included four partial
responses (4 PR), two minimal responses (2 MR), and 15 stable
disease (15 SD) assessments; two patients had progressive disease
(2 PD). The clinical benefit rate for patients treated at the
maximum tolerated dose of TH-302 (n=16 evaluable patients) was 31%
(comprised of 3 PR and 2 MR).
Poster Details
The poster titled, "Preliminary safety and efficacy of TH-302,
an investigational hypoxia-targeted drug, and dexamethasone in
patients with relapsed/refractory multiple myeloma" [Abstract #8534
(Poster #14)] is being presented at the Poster Highlights Session
on Lymphoma and Plasma Cell Disorders, 1:00 PM - 4:00 PM Central
Time, Friday, May 30, 2014, in Room S405; Discussion follows, 4:30
PM - 5:45 PM, Room S406.
Analyst Event with Clinical Experts on Sunday, June 1, 2014
Threshold will host an evening event for investors and analysts
on Sunday, June 1, 2014, at 6:00 PM Central Time at the Four
Seasons Hotel Chicago (120 East Delaware Place, Walton Room). The
event will include presentations highlighting TH-302 data presented
at ASCO. Guest speakers scheduled to give presentations include Dr.
Paul G. Richardson, Clinical Program Leader, Director of Clinical
Research, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer
Institute, R.J. Corman Professor of Medicine, Harvard Medical
School, Boston, Massachusetts, and Dr. Andrew J. Brenner, Clinical
Investigator with the Institute for Drug Development at the Cancer
Therapy & Research Center at The University of Texas Health
Science Center at San Antonio, Texas. RSVP to
lhansen@thresholdpharm.com.
The event is open to investors and analysts. Threshold invites
the public and the media to listen to the presentations via the
live webcast, which will be available under Webcasts in the
Investors section of www.thresholdpharm.com or can be accessed
using the following link:
http://psav.adobeconnect.com/thresholdpharmaceuticals/. The
presentations are scheduled to begin at approximately 6:15 PM
Central Time. A replay of the presentations will be archived on the
site for 30 days.
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 Designation 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 and
statements regarding the expected initiation of the final stage of
the ongoing Phase 1/2 trial. 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 results of human clinical
trials of TH-302; the risk that the final data from ongoing trials
may be materially different from the preliminary data that
Threshold has reported; Threshold's and Merck KGaA's (Darmstadt,
Germany) 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. Ghobrial IM, et al. Phase 1 study of TH-302, an
investigational hypoxia-targeted drug, and dexamethasone in
patients with relapsed/refractory multiple myeloma Blood
122:1948, 2013.
Contact Laura Hansen, Ph.D. Senior Director, Corporate
Communications Phone: 650-703-6523 E-mail:
lhansen@thresholdpharm.com
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