SAN DIEGO, June 27, 2018 /PRNewswire/ -- Trovagene, Inc.
(NASDAQ: TROV), a clinical-stage oncology therapeutics
company, developing targeted therapeutics for the treatment of
hematologic and solid tumor cancers, today announced preliminary
clinical data from the first dosing cohort showing a treatment
effect with PCM-075 in combination with low-dose cytarabine (LDAC)
or decitabine, as measured by decreases in leukemic cells in both
peripheral blood and bone marrow in patients in its ongoing Phase
1b/2 trial in relapsed or refractory
Acute Myeloid Leukemia (AML).
Both blood and bone marrow samples were obtained from patients
with relapsed or refractory AML enrolled in the Phase 1b/2 trial prior to, and at timepoints following
administration of PCM-075, in combination with cytarabine or
decitabine. In the first dose level, seven patients were treated
with PCM-075 at 12 mg/m2 in combination with either LDAC
or decitabine. One patient was not evaluable for safety due to
rapid disease progression. Among the other 6 patients, no
dose-limiting toxicities (DLTs) were observed that would prohibit
further escalation of the PCM-075 dosing. Three patients exhibited
substantial reductions in the percentage of both circulating
leukemic cells within the blood and leukemic cells within the bone
marrow. Two of these three patients continued on treatment in the
second cycle and further decreases in circulating leukemic cells in
the blood and within the bone marrow were observed. One patient had
a decrease in his bone marrow blasts from 96% to 40% at the end of
cycle 2 and has continued on treatment in cycle 3. The next dose
level cohort of PCM-075 at 18 mg/m2 in combination with
LDAC or decitabine is currently enrolling and dosing patients.
In addition, Translational Control Tumor Protein (TCTP), which
is uniquely phosphorylated by PLK1, was used to evaluate PLK1
inhibition by PCM-075. Data presented by Trovagene at the 2018
American Association for Cancer Research (AACR) showed that PCM-075
decreases phosphorylated TCTP (pTCTP) in AML cell lines. In these
same cell lines pTCTP levels were unaffected by treatment with
either LDAC or decitabine.
PLK1 inhibition in the Phase 1b/2
AML trial is being assessed in patients 3-hours following
administration of PCM-075 in combination with LDAC or decitabine,
when PCM-075 levels are expected to be at their peak concentration
(Cmax). Significant reductions in PLK1, as
measured by pTCTP levels, were observed in the circulating blood
cells in four of six patients treated with PCM-075 in combination
with cytarabine or decitabine. Three of these four patients
also had significant reductions in circulating blast cells during
the treatment cycle.
"While we are still quite early in the trial, these data points
are encouraging from both a safety and efficacy standpoint," said
Amer Zeidan, MBBS, MHS, Assistant
Professor of Medicine, Department of Medicine, and Yale Cancer
Center, Yale School of Medicine, Yale
University, a leading investigator on the trial.
"There were no dose limiting toxicities seen in the first cohort
and treatment was generally well tolerated. We know that treatment
with decitabine or low-dose cytarabine in patients with relapsed or
refractory AML is rarely effective, and the rare patients who do
respond usually require several cycles of therapy to do so. Seeing
substantial blast reductions in blood and bone marrow achieved in
several patients in the first one to two cycles at this first dose level of PCM-075, combined with
significant reductions in PLK1 activity as measured by pTCTP
levels, potentially suggests synergistic clinical activity with the
combination therapy. We remain excited to see how our patients will
do as we go to higher dose levels of PCM-075."
"In addition to the preliminary clinical data from our first
dose cohort, we are encouraged by the additional pharmacodynamic
data for patients in our Phase 1b/2
AML trial," said Dr. Mark Erlander,
Chief Scientific Officer of Trovagene. "This is the first time we
have observed a change in PLK1 status in patients during treatment
with PCM-075 in combination with either LDAC or decitabine."
About the PCM-075 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 PCM-075 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
PCM-075 in combination with standard-of-care chemotherapy. This
trial is being led by Hematologist 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,
Department of Medicine, and Yale Cancer Center, Yale School of Medicine, Yale University, New Haven, CT. Nine clinical sites are
currently activated in the U.S. and recruiting patients.
About PCM-075
PCM-075 is a highly-selective adenosine triphosphate (ATP)
competitive inhibitor of the serine/threonine polo-like-kinase 1
(PLK 1) enzyme, which is over-expressed in multiple hematologic and
solid tumor cancers. 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 up to 31% were observed when used in
conjunction 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 PCM-075 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 PCM-075 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. PCM-075 has been
granted Orphan Drug Designation by the FDA for the treatment of
patients with AML. Trovagene is enrolling a Phase 2 trial of
PCM-075 in combination with Zytiga®
(abiraterone acetate) and prednisone in metastatic
Castration-Resistant Prostate Cancer 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.
PCM-075 only targets the PLK1 isoform (not PLK2 or PLK3), is
orally available, has a 24-hour drug half-life with reversible
on-target hematologic toxicities. Trovagene believes that targeting
only PLK1 with reversible on-target activity and an improved
dose/scheduling protocol can significantly improve on the long-term
outcome observed in previous studies with a PLK inhibitor in
AML.
PCM-075 has demonstrated synergy in preclinical studies with
over 10 chemotherapeutic and targeted agents used in hematologic
and solid tumor cancers, including FLT3 and HDAC inhibitors,
taxanes, and cytotoxins. Trovagene believes the combination of its
targeted PLK1 inhibitor, PCM-075, with other compounds, has the
potential for improved 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 hematologic and solid tumor cancers.
About Trovagene, Inc.
Trovagene is a clinical-stage, oncology therapeutics company.
The Company's primary focus is to develop oncology therapeutics for
the treatment of hematologic and solid tumor cancers for improved
cancer care, utilizing its technology in tumor genomics. 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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