Aveo Oncology and partner Astellas Pharma Europe reported positive data from the pivotal Phase III study Viro-1, comparing the once-daily oral tyrosine kinase inhibitor candidate tivozanib with sorafenib in 517 patients with advanced renal cell carcinoma (RCC). Astellas says it plans to submit a marketing authorization application for tivozanib to the European authorities during the second half of 2012.
Tivo-1 enrolled patients with advanced clear cell RCC, who had undergone prior nephrectomy and had not previously been treated using a targeted therapy. The trial data showed that tivozanib therapy resulted in a median progression free survival of 12.7 months among previously treatment-naive metastatic RCC patients, compared with a median PFS of 9.1 months for patients treated using sorafenib. About 70% of the trial population fell into this category, and tivozanib is the first drug to generate more than one year median PFS in this patient subpopulation, Aveo and Astellas claim.
Among patients who had previously been treated with systemic therapy, including cytokines, tivozanib therapy led to a median PFS of 11.9 months, compared with a median PFS of 9.1 months for sorafenib therapy. The objective response rate for tivozanib was 33%, compared with 23% for sorafenib.
Tivozanib is Aveo’s lead product candidate, designed to selectively inhibit all three vascular endothelial growth factor receptors. In February 2011 the firm inked a worldwide deal, excluding Asia, to develop and commercialize the drug for the treatment of a broad range of cancers. Under terms of the deal Aveo is responsible for heading commercialization of tivozanib in North America, and Astellas will lead commercialization in the EU.
The firms are separately conducting clinical trials with tivozanib either as a single agent targeted therapy or in combination with other targeted therapies or chemotherapy in patients with RCC, breast, colorectal, and other cancers. The development program includes Baton (Biomarker Assessment of Tivozanib in Oncology), a series of clinical trials evaluating tivozanib biomarkers in solid tumors, as a means to identify patients most likely to respond to therapy.
In December 2011 Aveo started enrolling patients into an open-label, multicenter, randomized Phase II clinical trial, Baton-CRC, evaluating tivozanib in combination with modified FOLFOX6 (mFOLFOX6) compared to bevacizumab in combination with mFOLFOX6 as first-line therapy in patients with advanced metastatic colorectal cancer (CRC). Baton-RCC, a Phase II exploratory biomarker study in patients with advanced RCC, was started earlier in 2011.
Aveo’s second lead clinical candidate is ficlatuzumab (formerly AV-299), the most advanced antibody discovered using the firm’s Human Response Platform. Ficlatuzumab is a hepatocyte growth factor (HGF) inhibitor designed to block the HGF/c-Met pathway. Earlier this month the firm reported preliminary data from an exploratory Phase II study comparing gefitinib monotherapy with gefitinib plus ficlatuzumab in previously untreated Asian patients with non-small cell lung cancer. This population has a high prevalence of EGFR sensitizing mutations (SM+).
The study demonstrated evidence of activity in the relevant subset of patients based on EGFR mutation status and c-Met expression level, although the primary endpoint of overall response rate wasn’t met. Full data from the trial, including biomarker analyses, is expected to be presented later this year. Aveo says it also plans to start a study evaluating ficlatuzumab in patients with head and neck cancer by year end.
Aveo’s Human Response Platform has been developed to overcome the limitations of xenograft mouse models of cancer. The approach uses genetic engineering techniques to generate mice that develop spontaneous tumors exhibiting human-relevant, cancer-causing mutations that more closely mimic tumors in human patients.