On September 30, 2019 AVEO Oncology (NASDAQ: AVEO) reported that it has initiated enrollment in an open-label, multi-center Phase 1b/2 clinical trial evaluating FOTIVDA (tivozanib), the Company’s once-daily, potent and selective vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI), in combination with IMFINZI (durvalumab), AstraZeneca’s human monoclonal antibody directed against programmed death-ligand 1 (PD-L1), in patients with hepatocellular carcinoma (HCC) who have not received prior systemic therapy (Press release, AVEO, SEP 30, 2019, View Source [SID1234539950]).
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The study is expected to enroll approximately 50 patients. The Phase 1b portion will evaluate the safety, tolerability, dose limiting toxicity, maximum tolerated dose and preliminary anti-tumor activity starting with 1.0mg of tivozanib for 21 days followed by 7 days rest together with 1500mg of durvalumab every 28 days. Assuming satisfactory completion of the Phase 1b portion of the study, a Phase 2 expansion cohort will enroll at the dose schedule designated in Phase 1b. The primary outcome measure is incidence of treatment emergent adverse events. Secondary outcome measures include objective response rate per RECIST 1.1, progression free survival, duration of response, and overall survival. The trial is being conducted as part of a clinical collaboration between AVEO and AstraZeneca. AVEO is serving as the study sponsor, with study costs shared equally by both parties and clinical drug supplied by each respective company.
"HCC is the fastest rising cause of cancer-related death in the U.S., driven by prevalent diseases that include hepatitis B and C, nonalcoholic steatohepatitis and obesity. With five-year survival at approximately 26%, there remains a desperate need for new therapeutic options," said Michael Bailey, president and chief executive officer of AVEO. "VEGF TKIs and immunotherapy represent current standard of care monotherapies for advanced HCC, and we believe that the combination of tivozanib and durvalumab, both of which have demonstrated single agent activity in HCC, holds great promise as a potential new treatment option for this patient population. Tivozanib’s unique tolerability profile has the potential to make it an attractive VEGF TKI to combine with immunotherapy; in collaboration with AstraZeneca, we look forward to elucidating the potential of the tivozanib-durvalumab combination in patients with previously untreated advanced liver cancer."
About Tivozanib
Tivozanib (FOTIVDA) is an oral, once-daily, vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) 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 and selective inhibitor of all three VEGF receptors.1,2 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 Durvalumab
Durvalumab (IMFINZI) is a human monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80, countering the tumor’s immune-evading tactics and releasing the inhibition of immune responses.
Imfinzi is also approved for previously-treated patients with advanced bladder cancer in 10 countries, including the US.
As part of a broad development programme, Imfinzi is also being tested as a monotherapy and in combination with tremelimumab, an anti-CTLA4 monoclonal antibody and potential new medicine, as a treatment for patients with NSCLC, small cell lung cancer, bladder cancer, head and neck cancer, liver cancer, cervical cancer, biliary tract cancer and other solid tumours.