SAN DIEGO, July 9, 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 provided an update on
key value-creating milestones for the second half of 2018 and a
review of its year-to-date achievements.
"We continue to focus on advancing our two active clinical
trials with PCM-075; a Phase 1b/2
trial in patients with Acute Myeloid Leukemia (AML) and a Phase 2
trial in patients with metastatic Castration-Resistant Prostate
Cancer (mCRPC)," said Tom Adams,
Chairman of the Board and Interim Chief Executive Officer of
Trovagene. "We believe PCM-075 has the potential to address a
critical need for new treatment options for patients across a
variety of leukemias/lymphomas and solid tumor cancers."
"As a team, we achieved a number of key milestones in the first
half of 2018 and we continue to execute on our business plan and to
advancing our clinical development program in the second half of
2018. We are encouraged by the high level of interest from outside
parties and we are evaluating strategic development partnerships
for our drug asset outside the U.S."
Looking ahead to the second half of 2018, the Company's Board of
Directors is undertaking a search for a new CEO, who has the
relevant therapeutic and drug development experience to lead
Trovagene into its next stage.
Anticipated Second Half 2018
Milestones
Trovagene anticipates achieving the following milestones during
the second half of 2018:
Clinical Milestones for PCM-075
Phase 1b/2 trial of PCM-075 in
Combination with Either Low-Dose Cytarabine (LDAC) or Decitabine
for the Treatment of Acute Myeloid Leukemia (AML)
- Complete Phase 1b dose escalation
cohorts and identify the recommended Phase 2 dose (RP2D) for the
Phase 2 continuation trial (dependent upon the number of dose
escalation cohorts required to reach the maximum tolerated dose
(MTD) or recommended Phase 2 dose (RP2D) of PCM-075)
- Provide topline preliminary safety and efficacy data on the
combination of PCM-075 + LDAC and the combination of PCM-075 +
decitabine in patients treated through the end of 2018
- Present data from the AML trial at the 60th annual
American Society of Hematology (ASH) conference
- Initiate the Phase 2 segment of the AML trial, which will
enroll 32 patients for continued evaluation of safety and
preliminary efficacy of PCM-075 in combination with either LDAC or
decitabine (provided the RP2D has been determined in Phase
1b)
Phase 2 trial of PCM-075 in Combination with Abiraterone
Acetate (Zytiga®) and Prednisone for the Treatment of
Metastatic Castration-Resistant Prostate Cancer (mCRPC)
- Complete enrollment and cycle 1 of treatment of the 3 safety
lead-in patients with PCM-075 at 24 mg/m2 in combination
with abiraterone acetate (Zytiga®) and prednisone
- Evaluate the three lead-in patients in the mCRPC trial for
safety
- Provide topline preliminary safety and efficacy data of PCM-075
in combination with abiraterone acetate (Zytiga®) and prednisone in
patients treated through the end of 2018
First Half 2018 Achievements and
Highlights
Trovagene achieved important clinical milestones during the
first half of 2018, highlighted by the following
accomplishments:
- Announced Preliminary Clinical Data from First Dosing Cohort
Demonstrating Durable Treatment Effect of PCM-075 in Combination
with Cytarabine or Decitabine in Patients with Relapsed or
Refractory AML
On June 27,
2018, Trovagene 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. Among the 6 patients evaluated, 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.
- Announced the Start of Recruitment and Enrollment for Phase
2 Clinical Trial of PCM-075 in Combination with Zytiga® in Patients
with mCRPC
On June 21, 2018, Trovagene announced
they have received Institutional Review Board (IRB) approval from
Dana-Farber/Harvard Cancer Center and its Phase 2 clinical trial of
PCM-075 in combination with Zytiga® (abiraterone acetate) and
prednisone in metastatic Castration-Resistant Prostate Cancer
(mCRPC) is officially activated and recruiting patients. 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.
- Announced Completion of First Dosing Cohort of Patients
Treated with PCM-075 in Combination with Decitabine in Ongoing
Phase 1b/2 AML trial
On
June 15, 2018, Trovagene announced
completion of the first dose cohort of PCM-075, a highly-selective
Polo-like Kinase 1 (PLK1) Inhibitor, in combination with
decitabine, in its Phase 1b/2
clinical trial in patients with Acute Myeloid Leukemia (AML). Three
patients were treated with PCM-075 at 12 mg/m2, administered
orally, once daily, on days 1-5 of the treatment cycle, in
combination with decitabine. The combination of PCM-075 and
decitabine was well tolerated in all patients. The independent
Safety Review Committee (SRC) has recommended escalating to the
second dose cohort of three patients at 18 mg/m2 of
PCM-075 (approximately a 50% increase) in combination with
decitabine.
- Announced Completion of First Dosing Cohort of Patients in
Ongoing Phase 1b/2 AML trial of
PCM-075 in Acute Myeloid Leukemia
On May 17, 2018, Trovagene announced the completion
of the first dose cohort in its Phase 1b/2 clinical trial of PCM-075, a
highly-selective Polo-like Kinase 1 (PLK1) Inhibitor, in
combination with LDAC, in Acute Myeloid Leukemia (AML). Three
patients were treated with PCM-075 at 12 mg/m2,
administered orally, once daily, on days 1-5 of the treatment
cycle, in combination with LDAC. Patients eligible for Phase
1b have relapsed or refractory
disease and may have received as many as three prior regimens for
treatment of their AML. The combination of PCM-075 and LDAC was
well tolerated in all patients. The independent Safety Review
Committee (SRC) has recommended escalating to the second dose
cohort of three patients at PCM-075 at 18 mg/m2
(approximately a 50% increase) in combination with LDAC.
- Announced Presentation of Data at AACR Meeting 2018 on
Pharmacodynamic and Tumor Biomarkers During Treatment with PCM-075
and Low-Dose Cytarabine
On April 17,
2018, Trovagene announced the presentation of
pharmacodynamic and biomarker data from the first patient to
complete a safety treatment cycle in its Phase 1b/2 clinical trial of PCM-075, a
highly-selective Polo-like Kinase 1 (PLK1) Inhibitor, in Acute
Myeloid Leukemia (AML). The poster entitled Pharmacodynamic and
Tumor Biomarker Analysis of a PLK1 Inhibitor, PCM-075, in a Phase
1b/2 Trial for Acute Myeloid
Leukemia presents the methodology developed to track dynamic
changes in blood leukemic cells, genomic alterations and PLK1
inhibition in AML patients treated with PCM-075 in combination with
LDAC.
- Announced Presentation of data at AACR Meeting 2018 Showing
Synergy of PCM-075 in Combination with FLT3 Inhibitors in Acute
Myeloid Leukemia (AML)
On April 16,
2018, Trovagene announced the presentation of data showing
that PCM-075 exhibits synergistic activity when combined with FLT3
inhibitors in a human xenograft acute myeloid leukemia (AML) model,
at the American Association for Cancer Research (AACR) Annual
Meeting in Chicago, IL. The poster
entitled Selective Polo-like Kinase 1 (PLK1) Inhibitor PCM-075
is Highly Active Alone and Shows Synergy When Combined with FLT3
Inhibitors in Models of Acute Myeloid Leukemia (AML) presents
data demonstrating that PCM-075 in combination with quizartinib
(Daiichi-Sankyo) resulted in 97.3% tumor growth inhibition (TGI),
compared to 77.9% with quizartinib and 80.2% with PCM-075 as
monotherapy.
- Announced First Patient Successfully Completes Cycle 1 of
Treatment with PCM-075 in Combination with Low-Dose Cytarabine
(LDAC) in AML Trial
On March 5,
2018, Trovagene announced that the initial patient
successfully completed the first cycle 1 of treatment in its Phase
1b/2 multicenter trial of PCM-075 in
combination with low-dose cytarabine (LDAC) in patients with Acute
Myeloid Leukemia (AML). The patient tolerated the combination well
and correlative analyses of blood samples, taken at specified time
points, also indicated activity on leukemic blood cells. A
significant decrease in the percentage of blood leukemic cells was
observed within 24 hours of administering PCM-075 + LDAC. By day
15, within the treatment cycle, the greatest effect was observed
with blood leukemic cells showing a decrease from greater than 40%
to less than 5%. Additionally, the same tumor DNA mutations (ASXL1
and SRSF2) were detected in the bone marrow and blood, indicating
consistency across samples and validity of the analyses. Both DNA
mutations appeared to quantitatively track with the decrease in
blood leukemic cells.
- Announced Presentation of Data Showing Synergy of PCM-075 in
Combination with Zytiga® (abiraterone acetate) in
Castration-Resistant Prostate Cancer Model at 2018 Genitourinary
Cancers Symposium
On February 9,
2018, Trovagene announced that preclinical data
demonstrating the synergy of PCM-075, its highly-selective
Polo-like kinase 1 (PLK1) Inhibitor, in combination with
abiraterone acetate (Zytiga® – Johnson & Johnson), will be
featured as a Poster Presentation at the 2018 Genitourinary Cancers
Symposium on February 9th, from 12:15
– 1:45 PM and 6:00 – 7:00 PM PST, in San
Francisco, California. The poster entitled Combination of
Selective Polo-like Kinase 1 (PLK1) Inhibitor PCM-075 with
Abiraterone in Prostate Cancer and Non-Androgen-Driven Cancer
Models showcases data from Dr. Michael
Yaffe's lab at the Koch Institute for Integrative Cancer
Research at Massachusetts Institute of
Technology and will be presented by Dr. Jesse Patterson.
The underlying mechanism of synergy was further examined by
performing gene-expression comparison across more than 30 different
synergistic and non-synergistic cell lines across multiple tumor
types. From this analysis, multiple hypothesis-generating
mechanisms were identified, one of which was the retinoic acid
pathway, which when activated is predictive of synergy.
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 ZytigaÒ (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 target 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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SOURCE Trovagene, Inc.