First line cohort of the Phase 1b/2 DEDUCTIVE study demonstrates promising efficacy and tolerability of tivozanib plus durvalumab in first line HCC

Two trials in progress posters presentations for the DEDUCTIVE HCC study and the recently initiated Phase 1b/2 IMMCO-1 study of tivozanib and atezolizumab in multiple immunologically cold tumors

BOSTON, Jan. 20, 2022 (GLOBE NEWSWIRE) -- AVEO Oncology (Nasdaq: AVEO), a commercial stage, oncology-focused biopharmaceutical company, today announced that new efficacy and safety data from the first line (cohort A) of the phase 1b/2 DEDUCTIVE study of FOTIVDA^® (tivozanib) in combination with IMFINZI^® (durvalumab) in previously untreated metastatic hepatocellular carcinoma (HCC) are being presented at the 2022 American Society of Clinical Oncology Gastrointestinal (ASCO GI) Cancers Symposium. In addition, two trials in progress posters are being presented, which showcases cohort B of the DEDUCTIVE HCC study that is currently enrolling HCC patients following prior bevacizumab and atezolizumab; and the Company, in collaboration with the University of Florida Health Cancer Center, is presenting the study design for the Phase 1b/2 IMMCO-1 trial of atezolizumab plus tivozanib in immunologically cold pancreatic, gallbladder and biliary cancers.

“We believe that the safety and efficacy data observed in cohort A of the Phase 2 portion of the DEDUCTIVE study continue to support the development of tivozanib to serve as an attractive VEGFR TKI to use in combination with durvalumab in first line HCC patients,” said Michael Bailey, President and Chief Executive Officer of AVEO. “The poster presentations at this year’s ASCO GI conference reflect the expanding scope of our pipeline as we leverage the potential efficacy of our lead program tivozanib through a combination strategy targeting a number of cancers.”

Topline Efficacy and Safety Data Poster Title: A Phase 1b/2 Study of Tivozanib in Combination with Durvalumab in Subjects with Advanced Hepatocellular Carcinoma (DEDUCTIVE): Efficacy Results in Previously Untreated Patients (Abstract #462 / Poster: M10)

The Company will present topline data for cohort A of the DEDUCTIVE study, which is assessing the safety and efficacy of tivozanib in combination with IMFINZI^® (durvalumab), AstraZeneca’s human monoclonal antibody directed against programmed death-ligand 1 (PD-L1), in patients with unresectable locally advanced or metastatic, previously untreated HCC. A total of 20 patients with advanced or metastatic HCC were enrolled in cohort A of the Phase 2 portion of the study safety and efficacy of tivozanib plus durvalumab. Patients received 0.89 mg of tivozanib orally once daily for 21 days followed by seven days off therapy in combination with 1500 mg of durvalumab intravenously (IV) on day one given every four weeks, on a 28 day cycle. The combination was well tolerated, with three patients showing Grade 3 TRAEs, and no Grade 4 TRAEs or treatment-related deaths. The combination demonstrated a 27.8% partial response (PR) rate and disease control rate (PR + stable disease) 67.8%, with a median PFS of 7.3 months and a 1-year OS of 76%, which positions the tivozanib combination well relative to other VEGF ICI combinations in the setting.

Trials in Progress Poster Presentation titled: A Phase 1b/2 Open Label Study of Tivozanib in Combination with Durvalumab in Subjects with Advanced Hepatocellular Carcinoma: DEDUCTIVE - (Abstract: TPS499 / Poster: Online Only)

The DEDUCTIVE study is a multicenter, open-label study to evaluate the safety, tolerability, and efficacy of tivozanib in combination with durvalumab in subjects with advanced HCC previously untreated (cohort A) or bevacizumab- and atezolizumab-pretreated HCC (cohort B). Cohort A is fully enrolled and cohort B will enroll up to 20 subjects. Cohort A showed a promising safety and efficacy profile in previously untreated patients and cohort B has the potential demonstrate the first clinical study results in the emerging population of prior bevacizumab and atezolizumab treated patients.

The rationale for a combination therapy of tivozanib plus durvalumab to treat HCC draws on the potential synergistic mechanisms of tivozanib and durvalumab to remove inhibition of the immune response that mediates antitumor activity. The selectivity and favorable tolerability of the VEGFR TKI tivozanib may allow it to be used as a combination therapy with an immune checkpoint inhibitor, such as durvalumab.

The DEDUCTIVE trial is being conducted as part of a clinical collaboration between AVEO and AstraZeneca. AVEO is serving as the study sponsor.

Trials in Progress Poster Presentation titled: A phase 1b/2 study (IMMCO-1) of atezolizumab plus tivozanib in immunologically cold pancreatic, gallbladder, and biliary cancers – (Abstract: TPS491 / Poster: N8)

The ongoing IMMCO-1 study is an open-label, non-randomized Phase 1b/2 signal seeking basket study of the combination of the tivozanib and atezolizumab in multiple immunologically cold tumors, including pancreatic, gallbladder and biliary cancers. The co-primary endpoints are safety and efficacy. The Phase 1b portion will assess the safety profile of the combination of tivozanib and atezolizumab with a potential dose de-escalation of tivozanib using a 3+3 study design to yield a recommended Phase 2 dose.

VEGF is thought to play a key role in modulating the anti-tumor immune response. In addition, VEGF inhibits dendritic cell differentiation, limiting the presentation of tumor antigens to CD4 and CD8 T cells. Through the inhibition of VEGF, it may be possible to potentiate the effect of immune checkpoint blockade. Combined use of a VEGF tyrosine kinase inhibitor (TKI) and checkpoint inhibitor is already standard of care in advanced kidney, cervical and endometrial cancers. There has been suggestion that such a combination may have clinical activity in some microsatellite stable (MSS) GI malignancies.

The Phase 2 portion is expected to enroll up to 26 additional patients using the recommended Phase 2 dose using the Simon two-stage design of recruitment. This signal seeking study is looking to confirm the best objective response rate for evaluable patients increasing from < 7% (null hypothesis) to 25% (one-sided alpha = 0.05; 80% power).

The three posters to be presented at the 2022 ASCO GI Cancers Symposium are available on the Publications page of the AVEO Oncology website (click here). Details on the presentation are available on the 2022 ASCO GI website (click here).

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.² 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.³ 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,⁴ 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.

About AVEO Pharmaceuticals, Inc.

AVEO is a commercial-stage, oncology-focused biopharmaceutical company committed to delivering medicines that provide a better life for patients with cancer. AVEO currently markets FOTIVDA^® (tivozanib) in the United States for the treatment of adult patients with relapsed or refractory renal cell carcinoma (RCC) following two or more prior systemic therapies. AVEO continues to develop FOTIVDA in immuno-oncology combinations in RCC and other indications, and has other investigational programs in clinical development. AVEO is committed to creating an environment of diversity, equity and inclusion to diversify representation within the Company.

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,” “design,” “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 efficacy, safety and tolerability of tivozanib, both as a stand-alone drug candidate and in combination with other therapies in HCC, immunologically cold pancreatic, gallbladder and biliary cancers and other indications; AVEO’s plans, strategies and execution for current and future clinical trials of tivozanib; AVEO’s ability to timely enroll the DEDUCTIVE trial and the challenges arising from the COVID-19 pandemic and/or competitive factors that may impact such enrollment and completion timelines; the availability of data at the expected times; AVEO’s strategy, prospects, plans and objectives for tivozanib and for AVEO generally; the potential outcomes from studies of its product candidates to provide AVEO with opportunities to pursue regulatory strategies; the potential commercial opportunity of tivozanib and AVEO’s other product candidates. 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 and collaborators, to demonstrate to the satisfaction of applicable regulatory agencies such as the FDA the safety, efficacy and clinically meaningful benefit of tivozanib and tivozanib in combination with certain other therapies, and risks relating to the timing and costs of seeking and obtaining regulatory approvals; AVEO’s dependence on third-party vendors for the development, manufacture, supply, storage and distribution of tivozanib; 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’s and its collaborators’ ability to successfully enroll and complete clinical trials; AVEO’s ability to maintain compliance with regulatory requirements applicable to tivozanib; AVEO’s ability to obtain sufficient clinical supplies tivozanib; AVEO’s ability to obtain and maintain adequate protection for intellectual property rights relating to tivozanib; adverse general economic, political 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 commercialize FOTIVDA, manufacture clinical and commercial product and timely initiate new clinical trials or complete its ongoing clinical trials; competitive factors; and those risks discussed in the sections titled “Risk Factor Summary,” “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

1. Fotivda (Tivozanib) USPI March 2021

2. Fotivda (Tivozanib) SmPC August 2017

3. Motzer RJ, Nosov D, Eisen T, et al. J Clin Oncol 2013; 31(30): 3791-9

4. Pawlowski N et al. AACR 2013. Poster 3971

   

AVEO:
Hans Vitzthum
LifeSci Advisors, LLC
Hans@LifeSciAdvisors.com
(617) 430-7578

Source: AVEO Oncology