AVEO Oncology Announces Initiation of Topline Analysis of Phase 3 TIVO-3 Trial
Business Wire 1-Oct-2018 7:00 AM
- Analysis Initiated on the Unanimous Recommendation of the TIVO-3
Study Independent Steering Committee -
- Company Expects to Report Topline Results in Approximately 6 Weeks -
AVEO Oncology (NASDAQ:AVEO) today announced that it has initiated
topline analysis of the phase 3 TIVO-3 clinical trial on the unanimous
recommendation of the independent TIVO-3 Study Steering Committee, and
after notice to the FDA. The TIVO-3 trial is the Company's randomized,
controlled, multi-center, open-label study to compare FOTIVDA®
(tivozanib) to sorafenib in subjects with refractory advanced renal cell
carcinoma (RCC). The Company expects to complete data analysis and
report topline results from the study in approximately 6 weeks.
The Steering Committee recommendation was preceded by a slowing in the
rate of progression free survival (PFS) events in the trial over the
last 4-6 months. The reasons given by the Steering Committee for the
unanimous recommendation were that current patients have been on study
for at least one year and may not progress for some time, and that the
small reduction in events at the time of final analysis was unlikely to
materially affect the clinical interpretation of the results. As of
September 26, 2018, the last review of events, a total of 242 PFS events
had occurred in the trial. The Company plans to set the data cutoff date
for the primary analysis at October 4, 2018. Performing the primary
analysis at 242 events reduces the power of the study from 90% (based on
the prior target of 255 PFS events) to 88%.
Following the last review of events, 42 patients remain on treatment in
the TIVO-3 study with 28 of the remaining patients yet to have a PFS
event as determined by the independent radiology committee. All patients
still enrolled in the study will continue to receive treatment per study
protocol. The Company will remain blinded to study data until data
analysis is complete.
"Initiation of the topline analysis of the TIVO-3 trial brings us one
step closer to potentially realizing the strategy we laid out in 2015,
which included commercialization of tivozanib in the United States and
Europe, and exploration of tivozanib's clinical potential in
immunotherapy combinations," said Michael Bailey, president and chief
executive officer of AVEO. "With the introduction of immunotherapy as a
treatment for earlier-line RCC, survival among patients is extending
well beyond disease progression on first- and second-line treatment,
which we believe may substantially increase the third-plus-line
opportunity for tivozanib. TIVO-3 has the potential to serve as the
first prospective Phase 3 randomized dataset in this setting, creating
an evidence-based guidepost for sequencing therapies in refractory
disease. We look forward to announcing the topline results of TIVO-3 in
the coming weeks."
The TIVO-3 trial was designed to enroll patients with RCC who have
failed at least two prior regimens, including VEGFR-TKI therapy.
Eligible patients may also have received checkpoint inhibitor therapy in
earlier lines of treatment. Patients are randomized 1:1 to receive
either tivozanib or sorafenib, with no crossover between arms. The
primary endpoint of the study is PFS. Secondary endpoints include
overall survival (OS), overall response rate, and safety and
tolerability. TIVO-3, together with the previously completed TIVO-1
trial of tivozanib in the first-line treatment of RCC, is designed to
support a regulatory submission of tivozanib in the U.S. as a treatment
for RCC, if the data are positive. TIVO-3 patients were exclusively
enrolled in North America, Western Europe, and Central Europe.
About Tivozanib (FOTIVDA®)
Tivozanib (FOTIVDA®) is an oral, once-daily, vascular
endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI)
discovered by Kyowa Hakko Kirin and approved for the treatment of adult
patients with advanced renal cell carcinoma (RCC) in the European Union
plus Norway 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 has been shown to significantly reduce regulatory T-cell
production in preclinical models, enabling potentially enhanced activity
when used in combination with immune modulating therapy.3 As
part of a North American registration plan, tivozanib is currently being
studied in the Phase 3 TIVO-3 trial, a randomized, controlled,
multi-center, open-label study to compare tivozanib to sorafenib in
subjects with refractory RCC. Tivozanib has been investigated in several
tumors types, including renal cell, hepatocellular, colorectal and
breast cancers.
About AVEO
AVEO Pharmaceuticals, Inc. (the "Company") is a biopharmaceutical
company dedicated to advancing a broad portfolio of targeted medicines
for oncology and other areas of unmet medical need. The Company's
strategy is to retain North American rights to its oncology portfolio
while securing partners in development and commercialization outside of
North America. The Company is seeking to develop and commercialize its
lead candidate tivozanib in North America as a treatment for advanced
renal cell carcinoma ("RCC"). The Company has outlicensed tivozanib
(FOTIVDA®) for oncology in Europe and other territories outside of North
America. Tivozanib is approved in the European Union, as well as Norway
and Iceland, for the first-line treatment of adult patients with RCC and
for adult patients who are vascular endothelial growth factor receptor
and mTOR pathway inhibitor-naïve following disease progression after one
prior treatment with cytokine therapy for RCC. The Company has entered
into partnerships for the development and commercialization of AV-203
(CAN017) and ficlatuzumab, both clinical stage assets in oncology. The
Company is currently seeking a partner to develop the AV-353 platform, a
preclinical asset, worldwide for the potential treatment of pulmonary
arterial hypertension. The Company has recently regained the rights to
its AV-380 program for the potential treatment of cachexia and is
considering a variety of options to advance the program's development.
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 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 Company's expected timeline
to complete data analysis and report topline results from the TIVO-3
study; the expectation of the Steering Committee for the TIVO-3 trial
that the outcome of the primary study analysis is unlikely to change
with additional patient follow-up; the Company's plans and strategies
for commercialization of tivozanib in the United States and Europe; the
potential for tivozanib to have clinical potential in immunotherapy
combinations; the potential for TIVO-3 to serve as the first prospective
Phase 3 randomized dataset in the setting of immunotherapy, creating an
evidence-based guidepost for sequencing therapies in refractory disease;
the Company's plan to seek a partner to develop the AV-353 platform,;
the Company's plans regarding AV-380and AVEO's strategy, prospects,
plans and objectives. 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 to enter into and maintain
its third party collaboration and license agreements, and its ability,
and the ability of its collaborators, licensees and other strategic
partners, to achieve development and commercialization objectives under
these arrangements; and 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 tivozanib. AVEO faces
other risks relating to its business as well, including risks relating
to its and its collaborators' ability to successfully enroll and
complete clinical trials, including the TIVO-3 and TiNivo studies;
AVEO's ability to achieve and maintain compliance with all 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 and technologies; 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 section 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 may make with the SEC in the future. The
forward-looking statements in this press release represent AVEO's views
as of the date of this press release. AVEO anticipates that 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
1. Fotivda (Tivozanib) SmPC August 20172.
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.
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