On May 19, 2021 AVEO Oncology (Nasdaq: AVEO), a commercial and clinical development stage biopharmaceutical company, reported the presentation of additional data from the Phase 3 TIVO-3 study comparing FOTIVDA (tivozanib) to sorafenib in relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies (Press release, AVEO, MAY 19, 2021, View Source [SID1234580276]). The data, which includes updated durability of response (DOR) and overall survival (OS) results, as well as an analysis of treatment-emergent adverse events (TEAEs) across study arms, will be featured in two poster presentations at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting being held June 4-8 in a virtual setting. FOTIVDA, AVEO’s oral, next-generation vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI), is approved by the U.S. Food and Drug Administration for the treatment of adults with relapsed or refractory advanced RCC following two or more prior systemic therapies.

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"With advances in RCC treatment, patients are living longer, increasing the need for proven, well tolerated options in the relapsed or refractory setting," said Brian Rini, MD, Chief of Clinical Trials at Vanderbilt Ingram Cancer Center and principal investigator of the TIVO-3 trial. "The TIVO-3 study is the first positive Phase 3 study in RCC patients who received two or more prior systemic therapies, and these long-term follow up results continue to demonstrate the depth and durability of responses to FOTIVDA, as well as a tolerability profile that is particularly important in the later-stage treatment setting."

"FOTIVDA has demonstrated a differentiated clinical profile, and we are very pleased with initial receptivity to this differentiation and to the importance of the unique dataset that the TIVO-3 study represents in the commercial setting," said Michael Bailey, president and chief executive officer of AVEO. "We were also pleased to see efficacy advantages relative to sorafenib were maintained or improved with longer follow-up. We look forward to continuing to elucidate FOTIVDA’s potential in the clinic, particularly in the immunotherapy combination setting, with patient enrollment in the pivotal Phase 3 TiNivo-2 study of FOTIVDA in combination with OPDIVO (nivolumab) anticipated to commence mid-year and execution of the Phase 2 hepatocellular carcinoma DEDUCTIVE trial in combination with IMFINZI (durvalumab) ongoing."

TIVO-3 ASCO (Free ASCO Whitepaper) Data

TIVO-3 is a Phase 3, open-label study that enrolled patients with metastatic RCC whose disease progressed on two or more prior systemic regimens, one of which included a VEGFR TKI. Patients were stratified by International Metastatic RCC Database Consortium (IMDC) risk category (favorable, intermediate, or poor) and type of prior therapy (two prior VEGFR TKIs, VEGFR TKI plus checkpoint inhibitor, VEGFR TKI plus any other systemic agent) then randomized 1:1 to receive tivozanib or sorafenib. Results from the study were published in Lancet Oncology (December 2019). Additional analyses and long-term follow up results from the TIVO-3 study to be presented at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting include:

Durability of Response and Updated Overall Survival. Tivozanib demonstrated clinically meaningful and statistically significant improvements in overall response rate (ORR) and DOR compared to sorafenib in 350 patients randomized 1:1 with highly relapsed or refractory RCC. As of a January 15, 2021 data cutoff date, the median DOR for patients treated with tivozanib was 20.3 months (95% CI, 9.8-29.9 months) compared to 9.0 months (95% CI, 3.7-16.6 months) for patients treated with sorafenib. The ORR for patients treated with tivozanib was 23% compared to 11% for patients treated with sorafenib. Furthermore, long-term OS relative to sorafenib continues to improve (hazard ratio (HR): 0.91 [95% CI, 0.716-1.165; p=0.47]). The OS HR assesses the relative risk of death for the entirety of the data set.
Temporal Characteristics of Treatment-Emergent Adverse Events and Dose Modifications. Patients in the TIVO-3 study had longer duration of treatment exposure with tivozanib than sorafenib (11.9 cycles vs. 6.7 cycles), but fewer all-grade and grade ≥3 TEAEs. TEAEs were generally similar with tivozanib and sorafenib. Time to dose modifications was longer with tivozanib than sorafenib. Among those with the same TEAEs, dose reductions, interruptions, or discontinuations were required more frequently with sorafenib than tivozanib.
A copy of each poster will be available at www.aveooncology.com after its presentation at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting.

ASCO Presentation Details

Title: TIVO-3: Durability of response and updated overall survival of tivozanib versus sorafenib in metastatic renal cell carcinoma (mRCC).
Abstract: 4546
Track: Genitourinary Cancer—Kidney and Bladder
Date and Time: June 4, 2021 at 9:00 a.m. Eastern Time
Title: Temporal characteristics of treatment-emergent adverse events and dose modifications with tivozanib and sorafenib in the Phase 3 TIVO-3 study of relapsed or refractory mRCC.
Abstract: 4567
Track: Genitourinary Cancer—Kidney and Bladder
Date and Time: June 4, 2021 at 9:00 a.m. Eastern Time
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. FOTIVDA was approved in August 2017 in the European Union and other countries in the territory of its partner EUSA Pharma (UK) Limited for the treatment of adult patients with advanced RCC. FOTIVDA has been shown to significantly reduce regulatory T-cell production in preclinical models.1 FOTIVDA was discovered by Kyowa Kirin.

INDICATIONS

FOTIVDA is indicated for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hypertension and Hypertensive Crisis: Control blood pressure prior to initiating FOTIVDA. Monitor for hypertension and treat as needed. For persistent hypertension despite use of anti-hypertensive medications, reduce the FOTIVDA dose.

Cardiac Failure: Monitor for signs or symptoms of cardiac failure throughout treatment with FOTIVDA.

Cardiac Ischemia and Arterial Thromboembolic Events: Closely monitor patients who are at increased risk for these events. Permanently discontinue FOTIVDA for severe arterial thromboembolic events, such as myocardial infarction and stroke.

Venous Thromboembolic Events: Closely monitor patients who are at increased risk for these events. Permanently discontinue FOTIVDA for severe venous thromboembolic events.

Hemorrhagic Events: Closely monitor patients who are at risk for or who have a history of bleeding.

Proteinuria: Monitor throughout treatment with FOTIVDA. For moderate to severe proteinuria, reduce the dose or temporarily interrupt treatment with FOTIVDA.

Thyroid Dysfunction: Monitor before initiation and throughout treatment with FOTIVDA.

Risk of Impaired Wound Healing: Withhold FOTIVDA for at least 24 days before elective surgery. Do not administer for at least 2 weeks following major surgery and adequate wound healing. The safety of resumption of FOTIVDA after resolution of wound healing complications has not been established.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): Discontinue FOTIVDA if signs or symptoms of RPLS occur.

Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception.

Allergic Reactions to Tartrazine: The 0.89 mg capsule of FOTIVDA contains FD&C Yellow No.5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible patients.

ADVERSE REACTIONS

The most common (≥20%) adverse reactions were fatigue, hypertension, diarrhea, decreased appetite, nausea, dysphonia, hypothyroidism, cough, and stomatitis, and the most common Grade 3 or 4 laboratory abnormalities (≥5%) were sodium decreased, lipase increased, and phosphate decreased.

DRUG INTERACTIONS

Strong CYP3A4 Inducers: Avoid coadministration of FOTIVDA with strong CYP3A4 inducers.

USE IN SPECIFIC POPULATIONS

Lactation: Advise not to breastfeed.

Females and Males of Reproductive Potential: Can impair fertility.

Hepatic Impairment: Adjust dosage in patients with moderate hepatic impairment. Avoid use in patients with severe hepatic impairment.

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 FOTIVDA Full Prescribing Information which is available at www.FOTIVDA.com.

About Advanced Renal Cell Carcinoma

According to the American Cancer Society’s 2021 statistics, renal cell carcinoma (RCC) is the most common type of kidney cancer, which is among the ten most common cancers in both men and women. Approximately 73,750 new cases of kidney cancer will be diagnosed annually and about 14,830 people will die from this disease. In patients with late-stage disease, the five-year survival rate is 13%. Agents that target the vascular endothelial growth factor (VEGF) pathway have shown significant antitumor activity in RCC.2 According to a 2019 publication, 50% of the approximately 10,000 patients who progress following two or more lines of therapy choose not to receive further treatment,3 which may be attributable to tolerability concerns and a lack of data to support evidence-based treatment decisions in this highly relapsed or refractory patient population.