On January 19, 2018 AVEO Oncology (NASDAQ:AVEO) reported the presentation of data from a multicenter, Phase 1b/2 study of FOTIVDA (tivozanib), a potent, selective, long half-life inhibitor of all three vascular endothelial growth factor (VEGF) receptors, in patients with advanced, unresectable hepatocellular carcinoma (HCC) (Press release, AVEO, JAN 19, 2018, View Source;p=RssLanding&cat=news&id=2327533 [SID1234523364]). The data were presented during a poster session titled, "Phase 1b/2 study of tivozanib in patients with advanced inoperable hepatocellular carcinoma" (Abstract #364) at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium held January 18-20, 2018 in San Francisco. A copy of the presentation is available at www.aveooncology.com.

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"Advanced HCC represents an area of high unmet need, with the limited number of currently available therapies often associated with increased levels of hepatotoxicity, further complicating effective treatment," said Michael Needle, MD, chief medical officer of AVEO. "Findings from this study suggest that low doses of tivozanib may yield comparable PFS and a favorable response rate to current first line standards of care for HCC patients, with a favorable safety profile which may enable therapeutic combinations with immunotherapy. We expect the clinical investigation of the combination of VEGF and checkpoint inhibition to be the next critical step forward for the treatment of HCC. We look forward to reporting preliminary Phase 2 data from the TiNivo combination trial of tivozanib and nivolumab in the lead indication of renal cell cancer at the upcoming ASCO (Free ASCO Whitepaper) GU conference, and to exploring options for pursuing similar combinations in HCC."

The study, designed to evaluate the safety and efficacy of tivozanib in advanced HCC, enrolled a total of 21 patients at three study sites. In the Phase 1b portion of the trial, which used a modified 3+3 dose escalation design, 8 patients were dosed with tivozanib starting at 1.0 mg daily for 21 days followed by 7 days off drug, with inter-patient escalation to 1.5 mg daily or de-escalation to 0.5 mg daily based on cumulative dose-limiting toxicities (DLT). Upon escalation to 1.5 mg, two patients had on target dose limiting toxicities (grade 3 mucositis and hypertension), which were likely due to the high potency of tivozanib, and came off study without completing the DLT period. Tivozanib at 1.0 mg daily was selected for the Phase 2 expansion portion and was well tolerated.

Of 19 evaluable patients, at a median follow up of 16.9 months, the study’s primary endpoint of median progression-free survival (PFS) and PFS at week 24 were 5.5 months and 47%, respectively. A partial response (PR) was seen in 4/19 patients (21%) and stable disease (SD) in 8/19 patients (42%), for a disease control rate (DCR) of 63%. Overall survival (OS) at 6 and 12 months was 58% and 25%, respectively, with a median OS of 7.5 months. Notably, 4 patients have maintained SD for over two years. There were no significant changes in HBV or HCV viral load during study treatment. Tivozanib was generally well tolerated at 1.0 mg daily, with adverse events consistent with those observed in previous tivozanib trials.

The Phase 1b/2 study was one of several studies funded by a grant provided to the National Comprehensive Cancer Network from AVEO.

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 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. Tivozanib has been investigated in several tumors types, including renal cell, colorectal and breast cancers.