– The addition of nivolumab to low dose
tivozanib after prior immune checkpoint inhibitor (ICI) is not
superior to standard dose tivozanib alone; as a result, the primary
endpoint was not met –
– Tivozanib monotherapy (control arm)
results provide clinically meaningful efficacy and safety data
following front-line ICI combinations –
– Safety results reinforce tivozanib is
well-tolerated –
– Data to be submitted to upcoming
scientific meeting –
BOSTON, July 18,
2024 /PRNewswire/ -- AVEO Oncology, an LG Chem
company ("AVEO"), announced today that the TiNivo-2 Phase 3
clinical trial in patients with advanced metastatic renal cell
carcinoma (RCC) whose tumors had progressed following prior immune
checkpoint inhibitor (ICI) treatment did not meet the primary
endpoint of increasing progression free survival (PFS) when
nivolumab was added to low dose (0.89 mg)
FOTIVDA® (tivozanib). Importantly, the clinical
trial's control arm using FOTIVDA as monotherapy at the standard
dose (1.34 mg) demonstrated a clinically meaningful outcome in
median PFS in the second-line following ICI combination
therapy. These results build on the prior ICI dataset from the
TIVO-3 clinical trial, FOTIVDA's pivotal phase 3 study, and further
support the approved use of FOTIVDA as a safe and effective
treatment option in relapsed or refractory advanced RCC following
two or more prior systemic therapies.
![Aveo Oncology Logo (PRNewsfoto/AVEO, an LG Chem company) Aveo Oncology Logo (PRNewsfoto/AVEO, an LG Chem company)](https://mma.prnewswire.com/media/2108096/Aveo_Oncology_Logo.jpg)
The results from the TiNivo-2 clinical trial are consistent with
other recent RCC phase 3 trials in a similar patient population,
making this the second phase 3 clinical trial to suggest that there
is no clinical benefit derived from rechallenging RCC patients with
immunotherapy after receiving ICI beyond progression on previous
ICIs.
"The PFS and safety of the FOTIVDA control arm in the
second-line following ICI combinations adds to the growing body of
evidence of the importance of a highly selective anti-VEGFR
TKI therapy as an effective, well-tolerated treatment option for
relapsed or refractory RCC patients treated with prior ICI
combination therapy," says Michael P. Bailey, AVEO Oncology
Chief Executive Officer and President. "While the addition of an
ICI to low dose FOTIVDA did not improve PFS outcomes after prior
ICI, we consider the control arm data an important, evidence-based
and clinically meaningful contribution to the oncology community
treating relapsed or refractory advanced RCC following
front-line ICI combinations."
Toni Choueiri, M.D., Director of
the Lank Center for Genitourinary Oncology, Director of the Kidney
Cancer Center at Dana-Farber Cancer Institute, Jerome and Nancy
Kohlberg Chair and Professor of Medicine at Harvard Medical School, and lead investigator
comments, "The PFS and safety results from the control arm support
tivozanib as an effective and well-tolerated treatment option in
the second-line following an ICI combination as prior systemic
therapy."
The TiNivo-2 clinical trial was designed to evaluate the benefit
of adding nivolumab, a PD-1 checkpoint inhibitor, to low dose
FOTIVDA versus standard dose FOTIVDA in the second-line following
ICI combinations or the third-line setting following prior ICI. The
TiNivo-2 clinical trial enrolled patients across clinical sites
in North America, Latin
America, and Europe.
Patients with RCC who progressed after receiving immunotherapy were
randomized to either tivozanib single agent or in combination with
nivolumab. The trial's primary outcome was progression free
survival; secondary endpoints included overall survival, overall
response rate, duration of response, and safety.
Detailed findings are expected to be presented at an upcoming
medical meeting.
TiNivo-2 Clinical Trial Details
Phase 3 clinical trial
designed to evaluate the safety and efficacy of tivozanib in
combination with nivolumab, as compared to tivozanib as a
monotherapy, in RCC patients whose tumors have progressed
following prior immune checkpoint inhibitor therapy, known as the
TiNivo-2 trial.
About FOTIVDA® (tivozanib)
FOTIVDA® (tivozanib) is an oral, next-generation vascular
endothelial growth factor receptor (VEGFR) tyrosine kinase
inhibitor (TKI). It is a potent, selective inhibitor of VEGFRs 1,
2, and 3 with a long half-life designed to improve efficacy and
tolerability. AVEO received U.S. Food and Drug Administration (FDA)
approval for FOTIVDA on March 10,
2021, for the treatment of adult patients with relapsed or
refractory advanced renal cell carcinoma (RCC) following two or
more prior systemic therapies, based on data from the TIVO-3 trial
comparing FOTIVDA to sorafenib. FOTIVDA was approved in
August 2017 in the European Union and
other countries in the territory of its partner Recordati UK Ltd.
for the treatment of adult patients with advanced RCC. FOTIVDA was
discovered by Kyowa Kirin.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTION
Hypertension and Hypertensive Crisis: Hypertension
was reported in 45% of FOTIVDA-treated patients with 22% of the
events ≥Grade 3. Hypertensive crises were reported in
0.8% of patients. Do not initiate FOTIVDA in patients with
uncontrolled hypertension. Monitor for hypertension and treat as
needed. Reduce the FOTIVDA dose for persistent hypertension not
controlled by anti-hypertensive medications. Discontinue FOTIVDA
for severe hypertension that cannot be controlled with
anti-hypertensive therapy or for hypertensive crisis.
Cardiac Failure: Cardiac failures were reported in
1.6% of FOTIVDA-treated patients, with 1% of events reported as
≥Grade 3; 0.6% of events were fatal. Monitor for signs or symptoms
of cardiac failure throughout treatment with FOTIVDA. Manage with
dose interruption, dose reduction, or discontinuation.
Cardiac Ischemia and Arterial Thromboembolic
Events: Cardiac ischemia in FOTIVDA-treated patients were
reported in 3.2%; 0.4% of events were fatal. Arterial
thromboembolic events were reported in 2.0% of FOTIVDA-treated
patients, including death due to ischemic stroke (0.1%). Closely
monitor patients who are at risk for, or who have a history of
these events. Discontinue FOTIVDA in patients who develop severe
arterial thromboembolic events, such as myocardial infarction and
stroke.
Venous Thrombotic Events: Venous thromboembolic
events were reported in 2.4% of FOTIVDA-treated patients, including
0.3% fatal events. Closely monitor patients who are at increased
risk for these events. Discontinue FOTIVDA in patients who develop
serious venous thromboembolic events.
Hemorrhagic Events: Hemorrhagic events were reported
in 11% of FOTIVDA-treated patients; 0.2% of events were fatal.
FOTIVDA should be used with caution in patients who are at risk for
or who have a history of bleeding.
Proteinuria: Proteinuria was reported in 8% of
FOTIVDA-treated patients, with 2% Grade 3. Monitor throughout
treatment with FOTIVDA. For moderate to severe proteinuria, reduce
the dose or interrupt treatment with FOTIVDA. Discontinue FOTIVDA
in patients who develop nephrotic syndrome.
Thyroid Dysfunction: Thyroid dysfunction events were
reported in 11% of FOTIVDA-treated patients, with 0.3% of events
reported as ≥Grade 3. Monitor thyroid function before initiation
and throughout treatment with FOTIVDA.
Wound Healing Complications: Withhold FOTIVDA for at
least 24 days prior to elective surgery. Do not administer FOTIVDA
for at least 2 weeks after major surgery and until adequate wound
healing is observed. The safety of resumption of FOTIVDA after
resolution of wound healing complications has not been
established.
Reversible Posterior Leukoencephalopathy Syndrome
(RPLS): RPLS, a syndrome of subcortical vasogenic edema
diagnosed by MRI, can occur with FOTIVDA. Evaluate for RPLS in
patients presenting with seizures, headache, visual disturbances,
confusion, or altered mental function. Discontinue FOTIVDA if signs
or symptoms of RPLS occur.
Embryo-fetal Toxicity: FOTIVDA can cause fetal harm.
Advise patients of the potential risk to a fetus, to avoid becoming
pregnant and to use contraception during treatment and for one
month after the last dose of FOTIVDA. Advise males with female
partners of reproductive potential to use effective contraception
during treatment and for one month after the last dose of
FOTIVDA.
Allergic Reaction to Tartrazine: FOTIVDA 0.89 mg
capsule contains FD&C Yellow No. 5 (tartrazine) as an imprint
ink which may cause allergic-type reactions (including bronchial
asthma) in certain susceptible patients.
ADVERSE REACTIONS
The most commonly reported (≥20%) adverse reactions were:
fatigue/asthenia, hypertension, diarrhea, decreased appetite,
nausea, dysphonia, hypothyroidism, cough, and stomatitis. Serious
adverse reactions reported in >2% of patients included bleeding
(3.5%), venous thromboembolism (3.5%), arterial thromboembolism
(2.9%), acute kidney injury (2.3%), and hepatobiliary disorders
(2.3%).
DRUG INTERACTIONS
Strong CYP3A4 Inducers: Avoid coadministration of
FOTIVDA with strong CYP3A4 inducers.
USE IN SPECIFIC POPULATIONS
Lactation: Advise women not to breastfeed during
FOTIVDA treatment and for at least 1 month after the last dose.
Renal Impairment: The recommended dosage for
patients with end-stage renal disease has not been established.
Hepatic Impairment: Reduce the FOTIVDA dose for
patients with moderate hepatic impairment. The recommended dosage
in patients with severe hepatic impairment has not been
established.
To report SUSPECTED ADVERSE REACTIONS, contact AVEO
Pharmaceuticals, Inc. at 1-833-FOTIVDA (1-833-368-4832) or FDA at
1-800-FDA-1088 or www.fda.gov/medwatch.
Please see full Prescribing
Information for
FOTIVDA® (tivozanib).
About AVEO Pharmaceuticals, Inc.
AVEO is an oncology-focused biopharmaceutical company committed to
delivering medicines that provide a better life for patients with
cancer. AVEO currently markets FOTIVDA® (tivozanib) in the U.S. for
the treatment of adult patients with relapsed or refractory
advanced renal cell carcinoma (RCC) following two or more prior
systemic therapies. AVEO continues to develop FOTIVDA in
immuno-oncology and other novel targeted combinations in RCC and
other indications, and has other investigational programs in
clinical development. AVEO became a wholly owned subsidiary of LG
Chem Life Sciences USA, Inc. on
January 19, 2023. AVEO continues to
operate under the AVEO Oncology, an LG Chem company, name.
About LG Chem, Ltd. and LG Chem Life Sciences
LG Chem, Ltd. (LG Chem) is a leading global chemical company with a
diversified business portfolio in the key areas of petrochemicals,
advanced materials, and life sciences. The company manufactures a
wide range of products from high-value added petrochemicals to
renewable plastics, specializing in cutting-edge electronic and
battery materials, as well as drugs and vaccines to deliver
differentiated solutions for its customers. LG Chem Life Sciences
develops, manufactures, and globally commercializes pharmaceutical
products, with a focus on Oncology, Immunology, and Metabolic
diseases. Our mission is to transform people's lives through
inspiring science and leading innovation. For more information,
please visit www.lgchem.com.
References
- ClinicalTrials.gov. Study to Compare Tivozanib in
Combination with Nivolumab to Tivozanib Monotherapy in Subjects
with Renal Cell Carcinoma. Accessed July
12, 2024.
https://clinicaltrials.gov/ct2/show/NCT04987203
- FOTIVDA
(tivozanib)[https://www.fotivda.com/fotivdapi.pdf].Boston, MA: AVEO Pharmaceuticals, Inc.
- OPDIVO
(nivolumab)[https://packageinserts.bms.com/pi/pi_opdivo.pdf ].Princeton,
NJ: Bristol-Myers Squibb Company.
Contacts
Media:
John F. Kouten
JFK Communications, Inc.
jfkouten@jfkhealth.com
(908) 227-4714
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SOURCE AVEO, an LG Chem company