AVEO announces results from tivozanib Phase 1b clinical trial for advanced gastrointestinal cancers

AVEO Pharmaceuticals, Inc. (NASDAQ: AVEO), a biopharmaceutical company focused on discovering, developing and commercializing cancer therapeutics, today announced results from a Phase 1b clinical trial evaluating the company's lead product candidate, tivozanib, a highly potent and selective inhibitor of VEGF receptors 1, 2, and 3, in combination with FOLFOX6, a standard chemotherapy regimen, in patients with advanced gastrointestinal (GI) cancers. Results show partial responses in more than a third (35 percent) of patients evaluated>nd Annual Symposium of the European Organization for Research and Treatment of Cancer-National Cancer Institute-American Association for Cancer Research (EORTC-NCI-AACR) in Berlin, Germany.

“We believe the results from this Phase 1b trial evaluating tivozanib in combination with FOLFOX6 in patients with GI cancers further underscore the potential role tivozanib may play as a valuable addition to widely used chemotherapy regimens”

"Safe combinations of anti-cancer therapies may be critical to ensuring optimal treatment for patients with advanced gastrointestinal cancers, as toxicities associated with many currently available targeted therapies can limit opportunities for a combination approach," commented Ferry Eskens, M.D., Ph.D., department of medical oncology, Erasmus University Medical Center, Rotterdam, Netherlands, and lead investigator of the study. "The results observed in the tivozanib Phase 1b combination study with FOLFOX6 indicate encouraging anti-tumor activity and favorable tolerability in patients living with colorectal, pancreatic and esophageal cancers."

The Phase 1b open-label, dose-escalation study assessed once-daily, oral tivozanib (sequential cohorts of 0.5, 1.0, and 1.5 mg/day for three weeks on, one week off) and FOLFOX6 (IV every 14 days) in 22 patients with advanced gastrointestinal cancers who had been treated with no more than two prior chemotherapy regimens. FOLFOX6 is a standard chemotherapy regimen widely used to treat colorectal, pancreatic and esophageal cancers. For assessment of tolerability, treatment was continued for a minimum of four weeks, or until disease progression or unacceptable toxicity; for assessment of anti-tumor activity, treatment was continued for a minimum of eight weeks (two consecutive dosing cycles). Following are key results from the study:

• Partial responses were observed in six out of 17 patients evaluated, including one patient who experienced tumor shrinkage exceeding 50 percent, as evaluated by standard Response Evaluation Criteria in Solid Tumors (RECIST)
• Stable disease was observed in an additional eight out of the 17 patients evaluated using standard RECIST
• Treatment-related side effects seen in ≥ 20% of patients included nausea, fatigue, vomiting, constipation, decreased appetite, peripheral sensory neuropathy, headache, stomatitis, diarrhea and dysphonia
• Drug-related adverse events were not observed in association with the combination that were more frequent or severe than those observed in previous studies with FOLFOX6 or tivozanib alone

"We believe the results from this Phase 1b trial evaluating tivozanib in combination with FOLFOX6 in patients with GI cancers further underscore the potential role tivozanib may play as a valuable addition to widely used chemotherapy regimens," said William Slichenmyer, M.D., Sc.M., chief medical officer at AVEO. "To date, tivozanib has demonstrated full-dose combinability in Phase 1 clinical trials with other targeted and chemotherapy treatment options, including temsirolimus. These data, in addition to positive tivozanib Phase 2 monotherapy data in patients with advanced kidney cancer, indicate significant potential for tivozanib across multiple tumor types."

Preclinical Combination Data in Breast Cancer Model

Results from a preclinical study evaluating the activity of tivozanib and capecitabine, 5-fluorouracil (5-FU) and docetaxel, as single agents and in combination, in genetically engineered HER2 driven as well as traditional breast tumor models were also presented at the meeting. These data demonstrate that addition of capecitabine to tivozanib in a tivozanib resistant HER2 driven breast tumor model led to complete tumor growth inhibition (TGI), effectively reversing tivozanib resistance in the model. In the traditional breast tumor model, tivozanib monotherapy exhibited encouraging TGI, with modest improvements in TGI when combined with 5-FU or docetaxel. Following discontinuation of tivozanib alone or in combination with 5-FU, tumor regrowth was observed, whereas mice treated with tivozanib plus docetaxel were tumor-free by day 34 of the study, with no tumor recurrence at day 63.

Dr. Slichenmyer added, "We believe these preclinical data suggest tivozanib may be uniquely suited to combination therapy to potentially amplify treatment efficacy and combat drug resistance. We look forward to further understanding the potential utility of tivozanib as a treatment for breast cancer through ongoing and planned clinical trials."