SAN DIEGO, Nov.14, 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 prostate,
colorectal and leukemia, today announced new positive data from its
Phase 2 trial evaluating onvansertib in combination with
Zytiga® (abiraterone acetate - Johnson &
Johnson)/prednisone in patients with metastatic
Castration-Resistant Prostate Cancer (mCRPC). The data are being
presented today at the European Multidisciplinary Congress on
Urological Cancers (EMUC) in Vienna,
Austria.
"The new data shared today builds upon the encouraging clinical
response seen to date when onvansertib is added to treatment in
patients who have developed resistance to androgen receptor
signaling inhibitor (ARSi), Zytiga®," said Dr. Mark Erlander, Chief Scientific Officer of
Trovagene. "Of particular significance are the positive results we
are observing in patients who harbor the highly aggressive,
resistant variant of the androgen receptor (AR-V7). These patients
are resistant to ARS inhibitors including Zytiga® and Xtandi®
(enzalutamide - Pfizer) and their therapeutic options are not only
limited, but often ineffective. We believe the addition of
onvansertib has the potential to deliver transformative benefit to
patients with mCRPC by extending the duration of response to
treatment with ARS inhibitors."
Data Summary
The newly reported data include efficacy and safety assessments
as of the October 28, 2019 data
cut-off date for 15 patients that completed 3 months of treatment
and were eligible for evaluation of the primary efficacy endpoint
of disease control. Response to treatment was evaluated based on a
decrease or stabilization in prostate specific antigen (PSA) values
(primary endpoint) and confirmed by radiographic scans.
Efficacy
Overall, across both arms (A and B), a 60% response (SD + PR)
was observed in patients who were evaluable for efficacy (completed
3 months of treatment); 72% of patients had a decrease in PSA
following one cycle of treatment with onvansertib; 6 patients
remain on treatment for ≥4 months.
All 5 patients who tested positive for the highly-aggressive,
resistant AR-V7 variant had decreases in PSA following one cycle of
treatment with onvansertib; the primary efficacy endpoint (SD + PR)
was achieved in 3 out of 4 evaluable patients (completing 12 weeks
of treatment).
Safety
In both arms (A and B) onvansertib in combination with
abiraterone was safe and well-tolerated. The most frequent adverse
events (AEs) were expected, on-target (based on mechanism of action
of onvansertib) hematologic (anemia, neutropenia, thrombocytopenia
and white blood cell (WBC) decrease). All hematologic AEs were
easily and effectively managed and resolved by delaying or reducing
the dose and/or adding growth factor support. No unexpected
or off-target AEs have been reported to-date.
About the Phase 2 Trial of Onvansertib in mCRPC
The trial is a Phase 2 open-label multi-center study of
onvansertib in combination with Zytiga® (abiraterone
acetate)/prednisone in patients with mCRPC, showing signs of
disease progression and resistance to Zytiga® demonstrated by
two rising PSA values separated by at least one week, while on
Zytiga®(NCT03414034). The primary efficacy endpoint is the
proportion of patients achieving disease control after 12 weeks of
study treatment, as defined by lack of prostate specific antigen
(PSA) progression. The trial is being conducted by Beth Israel
Deaconess Medical Center (BIDMC), Dana-Farber Cancer Institute
(Dana-Farber), and Massachusetts General Hospital Cancer Center
(MGH). David Einstein, MD,
Genitourinary Oncology Program at BIDMC, is the principal
investigator for the trial.
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 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; 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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