AVEO Oncology (NASDAQ: AVEO) today announced that previously
reported data from its Phase 3 TIVO-3 study were published in The
Lancet Oncology. TIVO-3 is the Company’s Phase 3 randomized,
controlled, multi-center, open-label study to compare tivozanib
(FOTIVDA®), the Company’s vascular endothelial growth factor
receptor tyrosine kinase inhibitor (VEGFR-TKI), to sorafenib in 350
subjects with highly refractory metastatic renal cell carcinoma
(RCC). The article, titled “Tivozanib versus sorafenib in patients
with advanced renal cell carcinoma (TIVO-3): a phase 3,
multicentre, randomised, controlled, open-label study”, is
available online first via this link.
“TIVO-3 represents the first study to demonstrate a superior
progression free survival (PFS) benefit versus an active comparator
in patients with advanced or metastatic RCC who have failed at
least two prior lines of therapy, including a VEGFR-TKI, and the
first Phase 3 study to investigate a predefined subpopulation of
patients who received prior immunotherapy, the emerging standard of
care for earlier lines of therapy,” said Brian Rini, MD, Chief of
Clinical Trials at Vanderbilt Ingram Cancer Center, principal
investigator of the TIVO-3 trial, and lead author of the
publication. “Data from this study reinforce that tivozanib has the
potential to serve as an effective, tolerable therapy in the
evolving RCC treatment landscape.”
“With durable improvements observed in this highly refractory
RCC patient population, TIVO-3 offers valuable insight into the
potential sequencing of therapy following earlier TKI and
immunotherapy treatment,” said Michael Bailey, president and chief
executive officer of AVEO. “We are committed to maximizing the full
potential of tivozanib both as a monotherapy and in the
immunotherapy combination setting. We remain hopeful that the
overall survival hazard ratio will continue to improve ahead of the
final readout, expected in June 2020.”
“This agent has shown in clinical trials to be effective in
delaying cancer growth beyond established standards for patients
who have returning kidney cancer,” said Sumanta Pal, MD, a medical
oncologist at City of Hope and co-lead author of the new study.
“Although there are many options for patients with kidney cancer
today, most are intended for first- and second-line therapy. We
need a treatment that works for kidney cancer patients who have
failed several lines of therapy.”
AVEO recently provided a regulatory update following a meeting
with the U.S. Food and Drug Administration (FDA) to discuss results
from the August 2019 overall survival (OS) analysis of the TIVO-3
trial. The Company has submitted an update to the TIVO-3
statistical analysis plan to the FDA allowing for the final OS
analysis to be conducted, intends to submit a New Drug Application
(NDA) in the first quarter of 2020, and expects to report results
from the final OS analysis in June 2020. The FDA and the Company
agreed that if, during the review, the final analysis yields an OS
HR above 1.00, the Company will withdraw its NDA. The FDA informed
the Company that an Oncologic Drugs Advisory Committee panel would
likely be convened to review the final tivozanib data package.
Results in Detail
Patients enrolled in the TIVO-3 trial (n=350) were randomized
and stratified for prior regimen and IMDC prognostic score. Prior
treatment regimens included prior checkpoint inhibitor and VEGF TKI
therapies (n=91), two prior VEGF TKI therapies (n=159) and prior
VEGF TKI and other therapies (n=100). Statistically significant
improvements favoring tivozanib were reported for the primary
endpoint of PFS (HR=0.73; p=0.0165) and secondary endpoint of
overall response rate (18% vs. 8%; p=0.02).
As of the October 4, 2018 topline data analysis, in patients who
received prior checkpoint inhibitor and VEGF TKI therapies, 29 PFS
events occurred in the tivozanib group and 27 in the sorafenib
group. Median PFS was 7.3 months with tivozanib and 5.1 months with
sorafenib (HR 0.55, 95% CI 0.32–0.94). In this subpopulation, PFS
at one year was 37% (95% CI 0.22–0.51) with tivozanib and 5%
(0–0.14) with sorafenib. Two-year PFS was 28% (0.12–0.44) with
tivozanib. No patients in the sorafenib subgroup were progression
free at two years as of the October 4, 2018 data cutoff. In
patients who had previously received two prior VEGF TKI therapies,
56 PFS events occurred in the tivozanib group and 61 occurred in
the sorafenib group. Median PFS was 5.5 months tivozanib and 3.7
with sorafenib (HR 0.58, 95% CI 0.4–0.8).
For the secondary endpoint of OS, two prespecified analyses have
been conducted, the first at a data cutoff date of October 4, 2018,
and the second at August 15, 2019. The OS hazard ratio (HR), which
assesses the relative risk of death for the entirety of the data
set, was 0.99 (95% CI: 0.76-1.29; p=0.95) for the intent to treat
population at the second analysis, an improvement from an HR of
1.12 observed at the first analysis.
As of the August 15, 2019 data cutoff date, median OS, a point
in time value of the OS when half of the patients within each arm
are still alive, was 16.4 months for tivozanib (95% CI: 13.4-22.2)
and 19.7 months for sorafenib (95% CI: 15.0-24.2). As of the second
data cutoff date, twenty patients remained progression free on the
tivozanib arm and two on the sorafenib arm, with a median duration
on study of 32.5 months.
Grade 3 or higher adverse events were consistent with those
observed in previous tivozanib trials. Infrequent but severe
adverse events reported in greater number in the tivozanib arm were
thrombotic events similar to those observed in previous tivozanib
studies. The most common adverse event in patients receiving
tivozanib was hypertension, an adverse event known to reflect
effective VEGF pathway inhibition.
About Tivozanib (FOTIVDA®)
Tivozanib (FOTIVDA®) is an oral, once-daily, vascular
endothelial growth factor receptor (VEGFR) tyrosine kinase
inhibitor (TKI) discovered by Kyowa Kirin and approved for the
treatment of adult patients with advanced renal cell carcinoma
(RCC) in the European Union plus Norway, New Zealand and Iceland.
It is a potent, selective and long half-life inhibitor of all three
VEGF receptors and is designed to optimize VEGF blockade while
minimizing off-target toxicities, potentially resulting in improved
efficacy and minimal dose modifications.1,2 Tivozanib is being
studied in the TIVO-3 trial, which is intended to support a
regulatory submission of tivozanib in the U.S. as a treatment for
relapsed/refractory RCC. Tivozanib has been shown to significantly
reduce regulatory T-cell production in preclinical models3 and has
demonstrated synergy in combination with nivolumab (anti PD-1) in a
Phase 2 study in RCC4. Tivozanib has been investigated in several
tumor types, including renal cell, hepatocellular, colorectal,
ovarian and breast cancers.
About AVEO
AVEO Pharmaceuticals is a biopharmaceutical company seeking to
advance targeted medicines for oncology and other unmet medical
needs. The Company’s lead candidate is tivozanib, a potent,
selective, long half-life inhibitor of vascular endothelial growth
factor 1, 2 and, 3 receptors, which AVEO is seeking to develop and
commercialize in North America as a treatment for renal cell
carcinoma (RCC), hepatocellular carcinoma (HCC) and other cancers.
Tivozanib (FOTIVDA®) is approved by the European Commission for the
treatment of adult patients with advanced RCC in the European Union
plus Norway, New Zealand and Iceland. AVEO is leveraging or seeks
to leverage partnerships to develop and commercialize its pipeline
of products and product candidates, including tivozanib in oncology
and other indications in various geographies, and ficlatuzumab (HGF
MAb) in head and neck cancer, pancreatic cancer and acute myeloid
leukemia. AVEO’s earlier-stage pipeline includes AV-203 (anti-ErbB3
MAb), AV-380 (GDF15 MAb) and AV-353 (Notch 3 MAb) drug candidates
being developed for various oncology indications.
For more information, please visit the Company’s website at
www.aveooncology.com.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements of AVEO
within the meaning of the Private Securities Litigation Reform Act
of 1995 that involve substantial risks and uncertainties. All
statements, other than statements of historical fact, contained in
this press release are forward-looking statements. The words
“anticipate,” “believe,” “expect,” “intend,” “may,” “plan,”
“potential,” “could,” “should,” “would,” “seek,” “look forward,”
“advance,” “goal,” “strategy,” or the negative of these terms or
other similar expressions, are intended to identify forward-looking
statements, although not all forward-looking statements contain
these identifying words. These forward-looking statements include,
among others, statements about: the potential for tivozanib as a
treatment option for patients with relapsed/refractory or advanced
RCC; the potential efficacy, safety, and tolerability of tivozanib,
both as a stand-alone drug candidate and in combination with other
therapies in several indications; the potential for the TIVO-3 OS
HR to improve in the final OS analysis; AVEO’s plans and strategies
for commercialization of tivozanib in the United States and Europe;
and AVEO’s strategy, prospects, plans and objectives for its
product candidates and for the Company generally. AVEO has based
its expectations and estimates on assumptions that may prove to be
incorrect. As a result, readers are cautioned not to place undue
reliance on these expectations and estimates. Actual results or
events could differ materially from the plans, intentions and
expectations disclosed in the forward-looking statements that AVEO
makes due to a number of important factors, including risks
relating to: AVEO’s ability, and the ability of its licensees, to
demonstrate to the satisfaction of applicable regulatory agencies
such as the FDA the safety, efficacy and clinically meaningful
benefit of AVEO’s product candidates, including, in particular,
tivozanib and ficlatuzumab; AVEO’s ability to successfully file an
NDA for tivozanib; and AVEO’s ability to enter into and maintain
its third party collaboration and license agreements, and its
ability, and the ability of its strategic partners, to achieve
development and commercialization objectives under these
arrangements. AVEO faces other risks relating to its business as
well, including risks relating to the timing and costs of seeking
and obtaining regulatory approval; AVEO’s and its collaborators’
ability to successfully enroll and complete clinical trials; AVEO’s
ability to maintain compliance with regulatory requirements
applicable to its product candidates; AVEO’s ability to obtain and
maintain adequate protection for intellectual property rights
relating to its product candidates; AVEO’s ability to successfully
implement its strategic plans; AVEO’s ability to raise the
substantial additional funds required to achieve its goals,
including those goals pertaining to the development and
commercialization of tivozanib; unplanned capital requirements;
adverse general economic and industry conditions; competitive
factors; and those risks discussed in the sections titled “Risk
Factors” and “Management’s Discussion and Analysis of Financial
Condition and Results of Operations—Liquidity and Capital
Resources” included in AVEO’s quarterly and annual reports on file
with the Securities and Exchange Commission (SEC) and in other
filings that AVEO makes with the SEC. The forward-looking
statements in this press release represent AVEO’s views as of the
date of this press release, and subsequent events and developments
may cause its views to change. While AVEO may elect to update these
forward-looking statements at some point in the future, it
specifically disclaims any obligation to do so. You should,
therefore, not rely on these forward-looking statements as
representing AVEO's views as of any date other than the date of
this press release.
References
1. Fotivda (Tivozanib) SmPC August 2017 2. Motzer RJ, Nosov D,
Eisen T, et al. J Clin Oncol 2013; 31(30): 3791-9. 3. Pawlowski N
et al. AACR 2013. Poster 3971. 4. Barthelemy et al. ESMO 2018.
Poster 878P
View source
version on businesswire.com: https://www.businesswire.com/news/home/20191204005441/en/
AVEO Contact: David Pitts, Argot Partners (212) 600-1902
aveo@argotpartners.com
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