AVEO Announces Presentation of Updated OS and Subgroup Data from Phase 3 TIVO-3 Trial of Tivozanib in Renal Cell Carcinoma

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AVEO Announces Presentation of Updated OS and Subgroup Data from Phase 3 TIVO-3 Trial of Tivozanib in Renal Cell Carcinoma

- Tivozanib Significantly Improves PFS and ORR Compared to Sorafenib and Demonstrates Updated Interim OS HR of 0.99 in Refractory Advanced RCC -

- Outcomes Favor Tivozanib in Patients Previously Treated With Checkpoint Inhibitors as Well as Two VEGFR-TKIs -

- Data Featured in Oral Presentation at the 18th International Kidney Cancer Symposium -

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Nov. 18, 2019-- AVEO Oncology (NASDAQ: AVEO) today announced the presentation of updated data from the Phase 3 TIVO-3 trial. The data were presented on Saturday, November 16, 2019, at the 18th International Kidney Cancer Symposium in Miami, in an oral presentation titled “TIVO-3: A Phase 3 Study to Compare Tivozanib to Sorafenib in Subjects with Refractory Advanced Renal Cell Carcinoma (RCC) Overall Survival 2-Year Update” by Sumanta (Monty) Kumar Pal, M.D., Associate Clinical Professor, Department of Medical Oncology and Therapeutics Research, and Co-director, Kidney Cancer Program, at City of Hope Comprehensive Cancer Center. 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 RCC.

As previously presented, results for the intent to treat (ITT) population showed that tivozanib significantly improved progression free survival (PFS), the study’s primary endpoint, and overall response rate (ORR) compared to sorafenib, with responses to tivozanib more durable than sorafenib. Newly presented data include the recently announced interim overall survival (OS) hazard ratio (HR) of 0.99 within the ITT population, as well as results from two prespecified subgroup analyses of patients previously treated with a checkpoint inhibitor and a VEGF-TKI, or two VEGFR-TKIs. Superior PFS and ORR, as well as OS HRs below 1, favoring tivozanib, were observed in the prespecified subgroups. Tivozanib was shown to have lower overall rates of adverse events and fewer dose interruptions and reductions versus sorafenib, indicating better patient tolerability. A copy of the presentation is available in the Publications & Presentations section of AVEO’s website.

“Until the TIVO-3 trial results, limited prospective data existed to inform sequencing of treatment after checkpoint inhibitor therapy, the emergent standard of care in earlier-line treatment,” said Dr. Pal. “Tivozanib’s outcomes within this population, as well as in those receiving two prior VEGF-TKIs, suggest an important potential role for tivozanib in the evolving refractory advanced RCC setting. Furthermore, tivozanib’s unique tolerability profile is potentially well suited to an advanced setting, where many are reluctant to accept higher rates of adverse events following multiple courses of therapy.”

“Tivozanib is the first RCC treatment to show superior outcomes over another active therapy in a Phase 3 study in the third/fourth line setting, a high unmet need population that is growing due to longer survival in earlier lines of therapy,” said Michael Bailey, president and chief executive officer of AVEO. “We look forward to completing a final OS analysis of TIVO-3 in June 2020 after our planned submission of a new drug application (NDA) to the U.S. Food and Drug Administration (FDA) in the first quarter of 2020. The continued separation of the PFS curves and the positive trend in OS HR observed from the first to the second interim analyses of TIVO-3, together with tenfold more patients remaining progression free and on tivozanib vs. sorafenib therapy, make us believe that the final OS HR could continue to improve.”

AVEO recently provided a regulatory update following a meeting with the FDA to discuss results from the August 2019 OS analysis of the TIVO-3 trial. The Company intends to submit an update to the TIVO-3 statistical analysis plan to the FDA allowing for the final OS analysis to be conducted, followed by an NDA submission in the first quarter of 2020, and expects to report results from a final OS analysis of the TIVO-3 trial 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 application. 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 ORR (18% vs. 8%; p=0.02). Improvements were also observed in patients receiving prior checkpoint inhibitor and VEGF TKI therapies and two prior VEGF TKI therapies:

Prior Checkpoint Inhibitor + VEGFR TKI

Tivozanib

(n=47)

Sorafenib

(n=44)

Median PFS, months (95% CI)

7.3 (4.8, 11.1)

5.1 (3.2, 7.4)

PFS HR (95% CI)

0.55 (0.32, 0.94)

P Value

0.028

ORR

24.4%

6.8%

OS HR

0.88

Two Prior VEGFR TKIs

Tivozanib

(n=79)

Sorafenib

(n=80)

Median PFS, months (95% CI)

5.5 (3.6, 7.4)

3.7 (3.6, 3.9)

PFS HR (95% CI)

0.57 (0.39, 0.83)

P Value

0.003

ORR

15.2%

7.5%

OS HR

0.98

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 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 ITT population at the second analysis, and improvement from an HR of 1.12 observed at the first analysis. At the second analysis, OS HR for patients receiving prior checkpoint inhibitor and VEGF TKI therapies was 0.88, and 0.98 for patients treated with two prior VEGF TKI therapies. Both hazard ratios were improved from hazard ratios of 1.14 and 1.05, respectively, 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: AVEO’s plans to submit an update to the TIVO-3 statistical analysis plan to the FDA allowing for the final OS analysis to be conducted, followed by a planned NDA submission in the first quarter of 2020; AVEO’s expectations that it will report results from a final OS analysis of the TIVO-3 trial in June 2020; AVEO’s belief that the final OS HR in TIVO-3 could continue to improve; the potential for tivozanib as a treatment option for patients with relapsed/refractory or refractory advanced RCC, hepatocellular carcinoma and other cancers; the potential efficacy, safety, and tolerability of tivozanib, both as stand-alone drug candidate and in combination with other therapies ; AVEO’s expectation that TIVO-3 is intended to support a regulatory submission of tivozanib in the U.S. as a treatment for relapsed/refractory RCC; AVEO’s plans and strategies for commercialization of tivozanib in the United States and Europe; and AVEO’s other strategies, 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

Source: AVEO Oncology

AVEO:
David Pitts, Argot Partners
(212) 600-1902
aveo@argotpartners.com