SAN DIEGO, Oct. 1, 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 the
presentation of its Phase 1b/2 trial
evaluating onvansertib in combination with FOLFIRI and
Avastin® (bevacizumab) in patients with KRAS-mutated
metastatic Colorectal Cancer (mCRC).
The trial overview, featured in a poster presentation at
the European Society for Medical Oncology (ESMO) Annual Congress
showed the supportive preclinical data underlying the scientific
rationale for the trial, as well as the trial design and primary
safety and efficacy endpoints. In addition, early biomarker data
demonstrates proof-of-concept that patient response can be
monitored by a non-invasive blood test to quantitate the KRAS
mutation burden within one week following initial dosing with
onvansertib.
"Although early in the trial, the potential to bring a
much-needed new treatment option to patients with KRAS-mutated mCRC
with the combination of these drugs is promising," said
Heinz-Josef Lenz, MD, FACP,
Professor of Medicine, J. Terrence Lanni Chair in Gastrointestinal
Cancer Research, Co-Director, USC
Center for Molecular Pathway and Drug Discovery. "As of
September 1, 2019, four patients have
been treated and one has successfully completed their first cycle
of treatment. We believe onvansertib may provide clinical benefit
for patients who are faced with a poor prognosis and for whom
therapeutic options are limited."
Colorectal cancer (CRC) is the second leading cause of cancer
mortality in the U.S. Despite significant progress in the treatment
of mCRC, the majority of patients with metastatic disease succumb
to the disease. Therefore, improving the effectiveness of
treatments is critical in changing the outcomes for this patient
population. Approximately 50% of mCRC has the KRAS mutation. The
efficacy of second-line therapy in terms of survival prolongation
and response remains very limited, especially in this population,
where there is only a 5% response rate.
Presentation Highlights
Metastatic Colorectal Cancer:
- Tumor biomarkers drive therapy decisions for 1st and
2nd line mCRC therapy
- ~50% of mCRC is KRAS-mutated
- Standard second-line therapy in KRAS mutated patients is
chemotherapy (FOLFOX/FOLFIRI) + Bevacizumab
- Second-line therapies have only a ~5% response rate in
mCRC
Primary Endpoints:
- Phase 1b: Assess the safety and
preliminary efficacy of onvansertib in combination with FOLFIRI and
bevacizumab and identify the recommended Phase 2 dose (RP2D)
- Phase 2: Evaluate the efficacy of onvansertib in combination
with FOLFIRI and bevacizumab based on objective response rate (ORR)
in patients who receive at least 1 cycle (2 courses) of
treatment
About the Phase 1b/2 Clinical
Trial of Onvansertib in mCRC
The trial, A Phase
1b/2 Study of Onvansertib (PCM-075)
in Combination with FOLFIRI and Bevacizumab for Second‑Line
Treatment of Metastatic Colorectal Cancer in Patients with a
KRAS Mutation, will evaluate the safety and efficacy
of onvansertib in combination with standard-of-care FOLFIRI
and Avastin® (bevacizumab). Up to 44 patients, with a
confirmed KRAS mutation, metastatic and unresectable disease, who
have failed/intolerant of treatment with FOLFOX (fluoropyrimidine
and oxaliplatin) with or without Avastin® (bevacizumab), will
be enrolled. The trial is being conducted at two prestigious cancer
centers: USC Norris Comprehensive
Cancer Center and The Mayo Clinic Arizona.
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
Vice President Clinical Development and Investor Relations
858-952-7652
vkelemen@trovagene.com
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SOURCE Trovagene, Inc.