Date: 2015-06-30
Type of information: Presentation of results at a congress
phase: 2
Announcement: presentation of results at the European Society for Medical Oncology (ESMO) 17th World Congress on Gastrointestinal Cancer, taking place July 1-4 in Barcelona, Spain
Company: Aveo Oncology (USA - MA)
Product: tivozanib (N-{2-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N´-(5-methyl-3-isoxazolyl) urea hydrochloride monohydrate)
Action
mechanism: kinase inhibitor/tyrosine kinase inhibitor. Tivozanib is an oral, potent, selective inhibitor of vascular endothelial growth factor tyrosine kinase inhibitor (VEGF TKI) with a long half-life and activity against all three VEGF receptors.
Disease: metastatic colorectal cancer
Therapeutic area: Cancer - Oncology
Country:
Trial
details: The objective of this study is to compare the progression free survival (PFS), overall survival (OS), objective response rate (ORR), time to treatment failure (TTF), duration of response (DoR), quality of life, safety and tolerability of tivozanib in combination with mFOLFOX6 and bevacizumab in combination with mFOLFOX6. (NCT01478594)
Latest
news: * On June 30, 2015, Aveo Oncology announced that additional biomarker analyses from the BATON- (Biomarker Assessment of Tivozanib in ONcology) CRC study will be presented at the European Society for Medical Oncology (ESMO) 17th World Congress on Gastrointestinal Cancer, taking place July 1-4 in Barcelona, Spain. The presentation, titled “Neuropilin 1 (NRP1) may be Prognostic and Identify a Subgroup of Patients with Metastatic Colorectal Cancer (mCRC) who Benefit from Tivozanib + mFOLFOX6 compared to Bevacizumab + mFOLFOX6,” will be presented in an oral session titled “Session X: Presentation of Selected Abstracts: Colorectal Cancer,” which begins at 8:00 a.m. CEST on Friday, July 3, 2015, and in a poster session that begins at 10:25 a.m. CEST that day. As previously announced, the additional analyses, which produced similar results to those presented at the American Association for Cancer Research Tumor Angiogenesis and Vascular Normalization Conference in March 2015 used a different NRP1 assay and were conducted as part of the Company’s ongoing effort to develop an NRP1 assay suitable for further clinical study and eventual commercialization. Al B. Benson III, MD, FACP, Professor of Medicine at the Feinberg School of Medicine, Associate Director for Clinical Investigations at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, and principal investigator of the BATON-CRC study, will present the updated findings. * On March 6, 2015, Aveo Oncology announced the presentation of final results, including a predefined biomarker analysis, from the BATON- (Biomarker Assessment of Tivozanib in ONcology) CRC study, a randomized Phase 2 clinical trial of modified FOLFOX6 combined with tivozanib or bevacizumab in metastatic colorectal cancer (CRC). The presentation, titled “Neuropilin-1 as a potential biomarker of progression-free survival benefit for tivozanib + mFOLFOX6 versus bevacizumab + mFOLFOX6 in metastatic colorectal cancer: post-hoc biomarker analysis of BATON-CRC Phase 2 trial,” will be presented in a poster session today at the American Association for Cancer Research (AACR) Tumor Angiogenesis and Vascular Normalization Conference, taking place March 5-8, 2015, in Orlando, FL. Tivozanib is an oral, potent, selective inhibitor of vascular endothelial growth factor (VEGF) with a long half-life and activity against all three VEGF receptors. The BATON-CRC study enrolled a total of 265 patients randomized 2 to 1 to receive tivozanib in combination with mFOLFOX6 (n=177) compared to bevacizumab and mFOLFOX6 (n=88) as first-line treatment in patients with advanced metastatic CRC. A key objective of the BATON-CRC study is the assessment of prospectively defined biomarkers that may be predictive of response in selected patient subpopulations. Among these, patients with low neuropilin-1 (NRP-1) showed an improved progression free survival (PFS) versus patients with high NRP-1 in both treatment arms, supporting the value of NRP-1 as a potential prognostic marker for angiogenesis inhibitors. Further, patients with serum NRP-1 levels below the median demonstrated longer PFS when treated with tivozanib (17.9 months, n=52), compared to bevacizumab (11.2 months, n=28) (HR=0.380, p=0.0075), suggesting NRP-1 may have potential as a predictive biomarker of tivozanib activity relative to bevacizumab. Patients with high serum NRP-1 had PFS of 7.3 months and 7.5 months for the tivozanib and bevacizumab arms, respectively. With only 21 deaths in the NRP-1 low group upon study termination, no conclusion could be reached in an analysis of overall survival. An earlier, pre-specified interim futility analysis determined that tivozanib was unlikely to demonstrate superiority to bevacizumab in the primary endpoint of PFS in the intent to treat population (ESMO 2014), resulting in discontinuation of the study. The results presented today are the final results, and include five additional months of study conduct and patient follow-up beyond the data cutoff for the interim futility analysis. In the intent to treat population, the tivozanib and bevacizumab combinations demonstrated comparable results for PFS, the primary endpoint (9.8 months and 9.5 months for tivozanib and bevacizumab, respectively, HR=0.908, p=0.598), and overall response rate (46.9% and 43.2%, for tivozanib and bevacizumab, respectively), while demonstrating comparable safety. The most common toxicities included diarrhea, nausea, fatigue, neutropenia and hypertension. Serious adverse events were reported for 46.3% of patients in the tivozanib group and 48.3% in the bevacizumab group. * On September 29, 2014, Aveo Oncology announced poster presentations for two Phase 2 clinical studies of tivozanib, one in metastatic colorectal cancer (mCRC) and one in renal cell carcinoma (RCC), at the 2014 Congress of the European Society for Medical Oncology (ESMO), taking place September 25–30 in Madrid, Spain. BATON-CRC: a phase 2 randomized trial comparing tivozanib (tivo) + mFOLFOX6 with bevacizumab (bev) + mFOLFOX6 in stage IV metastatic colorectal cancer (mCRC): In this Phase 2, randomized, open-label trial (BATON-CRC), tivozanib plus mFOLFOX6 (Arm A, n=177) was compared to bevacizumab plus mFOLFOX6 (Arm B, n=88) in patients with previously untreated mCRC to demonstrate superiority over bevacizumab therapy. The primary endpoint was PFS by investigator radiologic assessment. Secondary endpoints included overall survival (OS), and objective response rate (ORR), among others. At a preplanned interim analysis, which included 95 PFS events, median PFS was 9.4 month for Arm A vs. 10.7 months for Arm B (HR=1.091, p=0.706) and ORR was 45% for Arm A vs. 43% for Arm B (p=0.718). There were no statistically significant associations between serum and/or tumor biomarkers and outcomes, although patients with high LDH (LDH ? 1.5 ULN, n=74), a prespecified biomarker, showed an encouraging PFS trend (HR=0.58, p=0.116), with approximately half of events reported at the interim analysis. The overall safety profile was comparable between arms. The most common toxicities included diarrhea, nausea, fatigue, neutropenia and hypertension. Serious AEs were reported for 46.3% of patients in the tivozanib group compared with 48.3% in the bevacizumab group. These interim results suggest that the combination of tivozanib plus mFOLFOX6 is comparable to bevacizumab plus mFOLFOX6 in the intent-to-treat population, with an acceptable safety profile. A prespecified interim futility analysis for superiority resulted in discontinuation of the study.
“These data demonstrate the potential for tivozanib, an oral therapy, to deliver similar results to standard-of-care therapy, bevacizumab, an IV therapy, when used in combination with FOLFOX in the intent-to-treat population,” said Al B. Benson III, MD, FACP, Professor of Medicine at the Feinberg School of Medicine, Associate Director for Clinical Investigations at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, and principal investigator of the study. “Given a promising trend in the predefined LDH high biomarker population at this interim analysis, I look forward to results from further follow-up in this study.”
