SAN DIEGO, Sept. 5, 2018 /PRNewswire/ -- Trovagene,
Inc. (NASDAQ: TROV), a clinical-stage oncology therapeutics
company, using a precision medicine approach to develop drugs for
the treatment of leukemias, lymphomas and solid tumor cancers,
today announced it has developed a method for predicting response
to treatment by measuring the ability of Onvansertib, a
first-in-class, 3rd generation, oral and
highly-selective Polo-like Kinase 1 (PLK1 ) inhibitor, to inhibit
PLK1 in patients with Acute Myeloid Leukemia (AML).
PLK1 uniquely phosphorylates translational control tumor protein
(TCTP) to form pTCTP and inhibition of this enzymatic activity by
Onvansertib appears to be predictive of patient response to
treatment. In the ongoing Phase 1b/2
open label clinical trial in AML, PLK1 inhibition is being assessed
3-hours following administration, at the approximate peak
concentration (Cmax) of Onvansertib. In the first six
patients treated, the greatest target engagement, or inhibition of
PLK1, was observed in the three patients who showed a response to
treatment.
"We are encouraged by these preliminary results and believe that
a simple blood test obtained 3-hours post-dose could enrich for
patients who are most likely respond to treatment with
Onvansertib," said Dr. Mark
Erlander, Chief Scientific Officer of Trovagene. "We
believe that integrating a predictive biomarker strategy into our
Onvansertib clinical development program may enable us to tailor
treatment to specific sub-groups of patients and have a positive
clinical impact."
Trovagene has filed a U.S. patent application with the United
States Patent and Trademark Office (USPTO) to protect its method
for evaluating responsiveness of a cancer to a Polo-like Kinase 1
(PLK1) inhibitor by determining the ability of the PLK1 inhibitor
to inhibit phosphorylation of a unique target of PLK1 in cells of
the cancer.
About the Onvansertib Phase 1b/2 Acute Myeloid Leukemia Trial
The Phase 1b/2 trial (NCT03303339)
is a multi-center, open-label trial to evaluate the safety and
efficacy of Onvansertib in combination with standard-of-care
chemotherapy in AML patients who are ineligible for intensive
induction therapy or whose disease is relapsed or refractory. In
Phase 1b dose-escalation segment of
the trial, the primary objective is to determine the maximum
tolerated dose (MTD) or recommended Phase 2 dose (RP2D), using a
traditional 3+3 design. In Phase 2 the MTD or RP2D will be
administered to 32 patients to evaluate preliminary antitumor
activity and to continue to evaluate the safety and tolerability of
Onvansertib in combination with standard-of-care chemotherapy. This
trial is being led by Jorge Cortes,
M.D., Deputy Department Chair, Department of Leukemia, Division of
Cancer Medicine, The University of
Texas MD Anderson Cancer Center and Amer Zeidan, MBBS, MHS, assistant professor of
Medicine at Yale School of Medicine,
Hematology expert at Yale Cancer Center. The trial is being
conducted at nine sites in the U.S.
About Onvansertib
Onvansertib is a first-in-class, 3rd generation, oral
and highly-selective adenosine triphosphate (ATP) competitive
inhibitor of the serine/threonine polo-like-kinase 1 (PLK 1)
enzyme, which is over-expressed in multiple cancers, including
leukemias, lymphomas and solid tumors. Separate studies with other
PLK inhibitors have shown that inhibition of polo-like-kinases can
lead to tumor cell death, including a Phase 2 study in Acute
Myeloid Leukemia (AML) where response rates of up to 31% were
observed when combined with a standard therapy for AML (low-dose
cytarabine-LDAC) versus treatment with LDAC alone with a 13.3%
response rate. A Phase 1 open-label, dose escalation safety study
of Onvansertib has been completed in patients with advanced
metastatic solid tumor cancers and published in Investigational
New Drugs. The maximum tolerated dose (MTD) or recommended
Phase 2 dose (RP2D) in this trial was 24 mg/m2.
Trovagene has an ongoing Phase 1b/2
clinical trial with Onvansertib in AML that was accepted by the
National Library of Medicine (NLM) and is now publicly viewable on
www.clinicaltrials.gov. The NCT number assigned by
clinicaltrials.gov for this study is NCT03303339. Onvansertib has
been granted Orphan Drug Designation by the FDA in the U.S. and by
the EC in the European Union (EU) for the treatment of patients
with AML. Trovagene is also enrolling a Phase 2 trial of
Onvansertib in combination with ZytigaÒ (abiraterone
acetate) and prednisone in metastatic Castration-Resistant Prostate
Cancer (mCRPC) that was accepted by the National Library of
Medicine (NLM) and is now publicly viewable on
www.clnincaltrials.gov. The NCT number assigned by
clinicaltrials.gov for this study is NCT03414034.
Onvansertib targets the PLK1 isoform (not PLK2 or PLK3), is
orally available, has a 24-hour drug half-life with only mild to
moderate side effects reported. Trovagene believes that targeting
only PLK1 and having a favorable safety and tolerability profile,
along with an improved dose/scheduling regimen will significantly
improve on the outcome observed in previous studies with a former
panPLK inhibitor in AML.
Onvansertib has demonstrated synergy in preclinical studies with
numerous chemotherapies and targeted therapeutics used to treat
leukemias, lymphomas and solid tumor cancers, including FLT3 and
HDAC inhibitors, taxanes, and cytotoxins. Trovagene believes the
combination of its targeted PLK1 inhibitor, Onvansertib, with other
compounds has the potential to improve clinical efficacy in Acute
Myeloid Leukemia (AML), metastatic Castration-Resistant Prostate
Cancer (mCRPC), Non-Hodgkin Lymphoma (NHL), Triple Negative Breast
Cancer (TNBC), as well as other types of cancer.
About Trovagene, Inc.
Trovagene is a clinical-stage, oncology therapeutics company,
using a precision medicine approach to develop drugs that target
mitosis (cell division) to treat various types of cancer, including
leukemias, lymphomas and solid tumors. Trovagene has intellectual
property and proprietary technology that enables the Company to
analyze circulating tumor DNA (ctDNA) and clinically actionable
markers to identify patients most likely to respond to specific
cancer
therapies. Trovagene plans to continue to vertically integrate
its tumor genomics technology with the development of targeted
cancer therapeutics. For more information, please visit
https://www.trovagene.com.
Forward-Looking Statements
Certain statements in this press release are forward-looking
within the meaning of the Private Securities Litigation Reform Act
of 1995. These statements may be identified by the use of words
such as "anticipate," "believe," "forecast," "estimated" and
"intend" or other similar terms or expressions that concern
Trovagene's expectations, strategy, plans or intentions. These
forward-looking statements are based on Trovagene's current
expectations and actual results could differ materially.
There are a number of factors that could cause actual events
to differ materially from those indicated by such forward-looking
statements. These factors include, but are not limited to,
our need for additional financing; our ability to continue as a
going concern; clinical trials involve a lengthy and expensive
process with an uncertain outcome, and results of earlier studies
and trials may not be predictive of future trial results; our
clinical trials may be suspended or discontinued due to unexpected
side effects or other safety risks that could preclude approval of
our product candidates; uncertainties of government or third party
payer reimbursement; dependence on key personnel; limited
experience in marketing and sales; substantial competition;
uncertainties of patent protection
and litigation; dependence upon third parties; our ability to
develop tests, kits and systems and the success of those products;
regulatory, financial and business risks related to our
international expansion and risks related to failure to obtain FDA
clearances or approvals and noncompliance with FDA regulations.
There are no guarantees that any of our technology or
products will be utilized or prove to be commercially successful,
or that Trovagene's strategy to design its liquid biopsy tests to
report on clinically actionable cancer genes will ultimately be
successful or result in better reimbursement outcomes.
Additionally, there are no guarantees that future clinical
trials will be completed or successful or that any precision
medicine therapeutics will receive regulatory approval for any
indication or prove to be commercially successful. Investors
should read the risk factors set forth in Trovagene's Form 10-K for
the year ended December 31, 2017, and other periodic reports
filed with the Securities and Exchange Commission. While the
list of factors presented here is considered representative, no
such list should be considered to be a complete statement of all
potential risks and uncertainties. Unlisted factors may
present significant additional obstacles to the realization of
forward-looking statements. Forward-looking statements
included herein are made as of the date hereof, and Trovagene does
not undertake any obligation to update publicly such statements to
reflect subsequent events or circumstances.
Trovagene Contact:
Vicki
Kelemen
VP, Corporate Communications
858-952-7652
vkelemen@trovagene.com
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SOURCE Trovagene, Inc.