AVEO Oncology (Nasdaq: AVEO) today announced that final overall
survival (OS) results from its Phase 3 TIVO-3 study were published
in the journal European Urology. TIVO-3 is the Company’s pivotal
Phase 3 trial comparing tivozanib, AVEO’s next-generation vascular
endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor
(TKI) drug candidate, to sorafenib in third and fourth line renal
cell carcinoma (RCC). The article, titled “Final Overall Survival
Results from a Phase 3 Study to Compare Tivozanib to Sorafenib as
Third- or Fourth-line Therapy in Subjects with Metastatic Renal
Cell Carcinoma,” is available online first via this link.
“TIVO-3 represents the first positive superiority study in the
growing population of patients who have relapsed or become
refractory to multiple lines of therapy, including checkpoint
inhibitors,” said Sumanta (Monty) Pal, MD, Associate Clinical
Professor, Department of Medical Oncology and Therapeutics
Research, and Co-director, Kidney Cancer Program, at City of Hope
Comprehensive Cancer Center, and lead author. “TIVO-3 data suggest
a favorable safety and efficacy profile relative to sorafenib as
demonstrated by superior anti-tumor progression free survival and
overall response activity vs. another VEGFR TKI, coupled with fewer
dose reductions, interruptions and discontinuations. The OS hazard
ratio (HR) is consistent with previous Phase 3 studies comparing
two VEGF-directed agents. I believe that tivozanib has the
potential to offer patients a meaningful new treatment option in a
setting currently lacking an evidence-based standard of care.”
“For RCC patients who have relapsed or are refractory to
multiple lines of therapy, the lack of well controlled clinical
data to guide treatment decisions in this advanced
relapsed/refractory population poses challenges for patients and
treating physicians,” said Michael Bailey, president and chief
executive officer of AVEO. “We expect that Tivozanib’s TIVO-3 data
has the potential to guide important treatment decisions in this
setting and ultimately improve outcomes and patient experience. We
look forward to working with the U.S. Food and Drug Administration
(FDA) as they continue to review our New Drug Application (NDA)
submission.”
In June 2020, AVEO announced that the FDA accepted for filing
its NDA seeking approval for tivozanib as a treatment for relapsed
or refractory RCC. The FDA has assigned the application standard
review and a Prescription Drug User Fee Act target action date of
March 31, 2021. The FDA also indicated that they do not currently
plan on convening an Oncologic Drug Advisory Committee (ODAC) to
discuss the application. The NDA submission is based on the TIVO-3
study and is also supported by three additional trials in RCC and
includes safety data from over 1,000 clinical trial subjects and
several years of commercial availability in Europe.
Results in Detail
Patients enrolled in the TIVO-3 trial (n=350) were randomized
and stratified by 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). As previously announced, the
TIVO-3 trial met the primary endpoint of progression free survival
(PFS), with a median PFS of 5.6 months in the tivozanib arm vs. 3.9
months in the sorafenib arm (HR=0.73; p=0.02), and the secondary
endpoint of overall response rate (ORR) (18% vs. 8%; p=0.02).
For the secondary endpoint of OS, the OS HR, which assesses the
overall relative risk of death, was 0.97 (95% CI: 0.75-1.24;
p=0.82), favoring tivozanib and improving from the previously
reported interim HR of 0.99. Median OS, representing a single point
in time in the OS curve, was 16.4 months for tivozanib (95% CI:
13.4-22.2) and 19.2 months for sorafenib (95% CI: 15.0-24.2). These
OS HR results are similar to those of prior VEGFR TKI vs. VEGFR TKI
studies in RCC.1-4
Tivozanib was found to be generally well-tolerated, with grade 3
or higher adverse events (AEs) consistent with those observed in
previous tivozanib trials. The most common AE in patients receiving
tivozanib was hypertension (38% vs. 25% for sorafenib, of treated
patients), an AE known to reflect effective VEGF pathway
inhibition. Infrequent but severe AEs reported in greater number in
the tivozanib arm were thrombotic events (5% vs. 4% for sorafenib,
of treated patients) similar to those observed in previous
tivozanib studies. Dose reductions and interruptions due to AEs
were significantly lower for tivozanib vs. sorafenib, despite
nearly double the average number of cycles initiated for the
tivozanib arm (11.9 months vs. 6.7 months for sorafenib), and
treatment related AEs leading to permanent discontinuation were 8%
for tivozanib vs. 15% for sorafenib.
About Tivozanib (FOTIVDA®)
Tivozanib is an oral, once-daily, next-generation vascular
endothelial growth factor receptor (VEGFR) tyrosine kinase
inhibitor (TKI) discovered by Kyowa Kirin and approved as FOTIVDA®
for the treatment of adult patients with advanced renal cell
carcinoma (RCC) in the European Union and other countries in the
EUSA territory. 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.5,6
Tivozanib is being studied in the TIVO-3 trial, which is supporting
a regulatory submission of tivozanib in the U.S. seeking marketing
approval as a treatment for relapsed or refractory RCC. Tivozanib
has been shown to significantly reduce regulatory T-cell production
in preclinical models7 and has demonstrated synergy in combination
with nivolumab (anti PD-1) in a Phase 2 study in RCC.8 Tivozanib
has been investigated in several tumor types, including renal cell,
hepatocellular, colorectal, ovarian and breast cancers. Tivozanib
is also being studied by partner Kyowa Kirin in non-oncology
indications.
About AVEO Pharmaceuticals, Inc.
AVEO is developing an oncology pipeline that is being designed
to provide a better life for patients with cancer. AVEO’s strategy
is to focus its resources toward development and commercialization
of its product candidates in North America, while leveraging
partnerships to support development and commercialization in other
geographies. AVEO’s lead candidate, tivozanib is approved as
FOTIVDA® in the European Union and other countries in the EUSA
territory for the treatment of adult patients with advanced renal
cell carcinoma. AVEO is working to develop and potentially
commercialize tivozanib in North America as a treatment for renal
cell carcinoma and hepatocellular carcinoma. AVEO has previously
reported promising early clinical data on ficlatuzumab (anti-HGF
mAb) in head and neck cancer, acute myeloid leukemia and pancreatic
cancer and is conducting a randomized Phase 2 confirmatory clinical
trial of ficlatuzumab in head and neck cancer. AVEO’s earlier-stage
pipeline includes several monoclonal antibodies in oncology
development, including AV-203 (anti-ErbB3 mAb), AV-380 (anti-GDF15
mAb) and AV-353 (anti-Notch 3 mAb). AVEO is committed to creating
an environment of diversity and inclusion as a foundation for
innovation.
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,” “hope,” “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 advanced HCC or
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; AVEO’s execution of its clinical and regulatory
strategy for tivozanib; AVEO’s plans and strategies for current and
future clinical trials of tivozanib, ficlatuzumab and AV-380 and
for commercialization of tivozanib in the United States; 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: whether the results of TIVO-3 are sufficient to obtain
marketing approval for tivozanib in the U.S., which turns on the
ability of AVEO to demonstrate to the satisfaction of the FDA the
safety and efficacy of tivozanib based upon the findings of TIVO-3,
including its data with respect to PFS, the rate of adverse events,
OS and other information that the FDA may consider to be relevant
to an approval determination; 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; 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,
including its ability to successfully launch and commercialize
tivozanib if it may be approved for commercialization by the FDA;
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; AVEO’s ability to access future borrowings under the
Hercules loan facility, which turns on the achievement of
milestones related to the approval and commercialization of
tivozanib in the U.S., which milestones may not be achieved;
adverse general economic and industry conditions; the potential
adverse effects of the COVID-19 pandemic on AVEO’s business
continuity, financial condition, results of operations, liquidity
and ability to successfully and timely enroll, complete and
read-out data from its clinical trials; 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.
Any reference to AVEO’s website address in this press release is
intended to be an inactive textual reference only and not an active
hyperlink.
References
- Hutson et al. Clinical Genitourinary Cancer; Vol. 15, No. 1,
72-6
- Choueiri et al. European Journal of Cancer 2018; 94:
115-125
- Motzer et. al. Lancet Oncol 2013; 14: 552–62
- Motzer, et al. N Engl J Med. 2014;370(18):1769-1770
- Fotivda (Tivozanib) SmPC August 2017
- Motzer RJ, Nosov D, Eisen T, et al. J Clin Oncol 2013; 31(30):
3791-9
- Pawlowski N et al. AACR 2013. Poster 3971
- Barthelemy et al. ESMO 2018. Poster 878P
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version on businesswire.com: https://www.businesswire.com/news/home/20200915006253/en/
AVEO Contact: David Pitts, Argot Partners (212) 600-1902
aveo@argotpartners.com
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