SAN DIEGO, Oct. 2, 2019 /PRNewswire/ -- Trovagene,
Inc. (Nasdaq: TROV), a clinical-stage, Precision Cancer
Medicine™ oncology therapeutics company developing drugs that
target cell division (mitosis) for the treatment of various cancers
including breast, prostate, colorectal and leukemia, today
announced the presentation of preclinical data demonstrating
significant tumor regression with the combination of onvansertib
and paclitaxel, versus either agent alone, in models of
triple-negative breast cancer (TNBC).
The data was featured in a poster presentation at the
European Society for Medical Oncology (ESMO) Annual Congress on
Sunday, September 29th,
2019.
"The development of new options to treat TNBC that is resistant
to standard-of-care chemotherapy can address a critical unmet
clinical need," said Antonio
Giordano, MD, PhD, medical oncologist at Medical University of South Carolina (MUSC). "We
value our collaboration with Trovagene, and we believe that our
preclinical data confirms the potential therapeutic benefit of
onvansertib and warrants further evaluation. Planning for the
initiation of a clinical trial targeting TNBC patients with the
highly-aggressive p53 mutation is currently underway at MUSC."
TNBC is an aggressive form of the disease accounting for 12 to
18% of breast cancers. Although chemotherapy can be effective as
standard-of-care, many patients become resistant to treatment. The
TP53 gene is mutated in approximately 80% of TNBC and the mutation
is considered a target marker. TNBC is defined by the absence of
estrogen and progesterone receptors and the absence of HER2
overexpression. These cancers represent a heterogeneous breast
cancer subtype with a poor prognosis. Few systemic treatment
options exist besides the use of chemotherapy. Currently, there are
no approved targeted therapies to treat TNBC.
Presentation Highlights
Background:
- Somatic mutation in TP53 gene (mutp53) is a strong prognostic
marker in breast cancer
- Triple negative breast cancer (TNBC) is characterized by up to
80% mutp53 and the greatest overall genomic instability among
subtypes
- Polo-like kinase 1 (PLK1) regulates progression of cells
through the G2 phase of the cell cycle
- Hypothesis that mutp53 in the context of breast cancer can
predict synergy to paclitaxel plus onvansertib, an orally available
highly selective PLK1 inhibitor
Significant Clinical Need for New Targeted Treatment Option
(Onvansertib + Paclitaxel):
- Cell lines undergo G2/M cell-cycle arrest following PLK1
(onvansertib) inhibition
- Paclitaxel synergizes with onvansertib (the activity of the two
drugs together is greater than that of each drug alone) and induces
apoptosis (death) of cancer cells
- Currently, treatment options are limited to chemotherapy and
there is a significant medical need to develop a targeted
therapeutic option for the treatment of breast cancer patients with
TP53 mutation
- A clinical study to assess the safety and preliminary efficacy
of the combination of onvansertib and paclitaxel as a potential new
targeted treatment option in TNBC is warranted
About Onvansertib
Onvansertib is a first-in-class, third-generation, oral and
highly-selective adenosine triphosphate (ATP) competitive inhibitor
of the serine/threonine polo-like-kinase 1 (PLK1) enzyme, which is
over-expressed in multiple cancers including leukemias, lymphomas
and solid tumors. Onvansertib targets the PLK1 isoform only (not
PLK2 or PLK3), is orally administered and has a 24-hour 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 irinotecan,
FLT3 and HDAC inhibitors, taxanes and cytotoxins. Trovagene
believes the combination of 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), colorectal cancer and
triple-negative breast cancer (TNBC), as well as other types of
cancer.
Trovagene has three ongoing clinical trials of onvansertib: A
Phase 2 trial of onvansertib in combination with Zytiga®
(abiraterone acetate)/prednisone in patients with mCRPC who are
showing signs of early progressive disease (rise in PSA but
minimally symptomatic or asymptomatic) while currently receiving
Zytiga® (NCT03414034); a Phase 1b/2
Study of onvansertib in combination with FOLFIRI and
Avastin® for second-line treatment in patients with mCRC with
a KRAS mutation (NCT03829410); and a Phase 1b/2 clinical trial of onvansertib in combination
with low-dose cytarabine or decitabine in patients with relapsed or
refractory AML (NCT03303339). Onvansertib has been granted orphan
drug designation by the FDA in the U.S. and by the EC in the
European Union for the treatment of patients with AML.
Trovagene licensed onvansertib (also known as NMS-1286937 and
PCM-075) from Nerviano Medical Sciences (NMS), the largest
oncology-focused research and development company in Italy, and a leader in protein kinase drug
development. NMS has an excellent track record of licensing
innovative drugs to pharma/biotech companies, including Array
(recently acquired by Pfizer), Ignyta (acquired by Roche) and
Genentech.
About Trovagene, Inc.
Trovagene is a a clinical-stage, Precision Cancer
Medicine™ oncology therapeutics company developing drugs that
target cell division (mitosis), for the treatment of various
cancers 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.trovageneoncology.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. 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, 2018,
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, Clinical Development and Investor Relations
858-952-7652
vkelemen@trovagene.com
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