VeriStrat “Poor” Patients Show Encouraging Overall Survival and Progression Free Survival Signal; Confirmatory Phase 2 Study Planned by Year-End
MADRID, Spain I September 29, 2014 I AVEO Oncology (NASDAQ:AVEO) and Biodesix, Inc. today announced the presentation of results from a retrospective exploratory analysis using VeriStrat®, a commercially available serum protein test, to identify patients most likely to benefit from the addition of ficlatuzumab, AVEO’s HGF inhibitory antibody, to epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor (TKI) therapy in a randomized Phase 2 study of ficlatuzumab and gefitinib (IRESSA®) in previously untreated Asian subjects with non-small cell lung cancer (NSCLC). The results, presented in a poster session (abstract #8195) at the 2014 Congress of the European Society for Medical Oncology (ESMO), suggest that VeriStrat may be selective of positive clinical response for ficlatuzumab plus gefitinib over gefitinib alone.
“EGFR TKIs are an important class of therapy for which VeriStrat has potential prognostic and predictive value,” said Tony Mok, M.D., Professor, Department of Clinical Oncology, The Chinese University of Hong Kong, and senior investigator of the study. “VeriStrat appears to measure a host response in which tumors may become stimulated by alternative pathways, such as HGF/c-MET, leading to resistance to EGFR TKI therapy. In this exploratory analysis, the addition of the HGF-targeted antibody ficlatuzumab to an EGFR TKI therapy has shown encouraging results in this subgroup, including significant improvements in overall survival and progression free survival.”
Exploratory Analysis Results in Detail
A total of 188 patients were enrolled in a randomized Phase 2 study (P6162) designed to compare the combination of ficlatuzumab and gefitinib with gefitinib alone in treatment-naïve Asian patients with non-small cell lung adenocarcinoma. For this retrospective exploratory analysis, 180 serum samples were assigned a VeriStrat label of either “Good” (VSG) or “Poor” (VSP) (VSG=145, VSP=35). While the study failed to demonstrate improved overall survival (OS) or progression-free survival (PFS) over gefitinib alone in the intent-to-treat population, the addition of ficlatuzumab to gefitinib provided significant clinical benefit to the VSP subgroup:
| VSP |
|
ficlatuzumab and
gefitinib
n=18
|
|
gefitinib alone
n=17
|
| OS |
Median |
|
23.9 months |
|
5.8 months |
| Hazard Ratio |
|
0.41 |
| p-value |
|
0.032 |
| PFS |
Median |
|
7.4 months |
|
2.3 months |
| Hazard Ratio |
|
0.41 |
| p-value |
|
0.014 |
No benefit was observed in the VSG subgroup in either OS (Median 24.7 mo for ficlatuzumab + gefitinib [n=69] vs not reached for gefitinib alone [n=76]; HR 1.18, p=0.492) or PFS (Median 5.6 mo for ficlatuzumab + gefitinib vs 5.6 mo for gefitinib alone; HR 1.06, p=0.753). Despite the small sample sizes, similar patterns in OS and PFS based on VeriStrat stratification were also observed in patients with known EGFR mutations (n=71) and VSP classification (n=11):
| VSP and EGFRm |
|
ficlatuzumab and
gefitinib
n=5
|
|
gefitinib alone
n=6
|
| OS |
Median |
|
17.8 months |
|
10.4 months |
| Hazard Ratio |
|
0.3 |
| p-value |
|
0.09 |
| PFS |
Median |
|
11.1 months |
|
2.3 months |
| Hazard Ratio |
|
<0.01 |
| p-value |
|
<0.01 |
Based on these data, in April 2014, AVEO and Biodesix® entered into a worldwide agreement to develop and commercialize ficlatuzumab with a Biodesixcompanion diagnostic test. As part of this agreement, AVEO and Biodesix plan to conduct a confirmatory Phase 2 study using a Biodesix VeriStrat “Poor” classification as a selective biomarker for the combination of ficlatuzumab and an EGFR-TKI, versus an EGFR TKI alone, in previously untreated, EGFR mutation-positive patients with advanced non-small-cell lung cancer. The study is expected to initiate before year-end.
“This analysis suggests that VeriStrat Poor, EGFR TKI-sensitizing mutation-positive patients with NSCLC appear to have limited response to EGFR TKI alone, identifying a significant unmet medical need,” stated Tuan Ha-Ngoc, president and chief executive officer of AVEO. “Given our scientific hypothesis, and the encouraging results in this well-defined patient subset, we believe further clinical evaluation of ficlatuzumab and an EGFR TKI therapy in this population is warranted.”
“These results suggest that a blood test may be used to more precisely classify the response of a subset of patients who, based on EGFR mutation status, should be candidates for an EGFR inhibitor yet appear not to respond to the mono-therapy without the addition of ficlatuzumab,” said David Brunel, chief executive officer of Biodesix. “By using biomarkers and Biodesix’ proprietary ‘predictive intelligence’ computational approach, we believe we can further identify patient sub-populations with differential predictive and prognostic outcomes to advance decisions for therapeutic guidance. Biomarkers are empowering oncologists and the healthcare community with an evidence-based medical approach that informs more precise decisions on diagnosis, prognosis, therapeutic guidance and quality of patient care.”
A copy of the poster presentation is available on AVEO’s website at www.aveooncology.com.
About Ficlatuzumab and the HGF/c-Met Pathway
HGF is the sole ligand that binds to and activates a receptor called c-Met. Activation of the HGF/c-Met pathway is believed to be important in normal processes in embryonic development and wound healing, but its dysregulation is believed to play a role in cancer development, metastasis and drug resistance. HGF/c-Met has also been shown to be one of the most potent drivers of tumor growth in AVEO’s Human Response Platform™.
HGF/c-Met over-expression is observed in many solid tumors including breast, colorectal, gastric, head and neck, lung and prostate, as well as hematologic malignancies. Additionally, c-Met and EGFR are frequently co-amplified and co-expressed in a variety of tumor types; HGF/c-Met pathway upregulation can render resistance to EGFR-targeted therapies, and vice-versa. HGF has also been shown to be one of the most potent growth factors that can drive resistance to a panel of anti-cancer therapies.
Ficlatuzumab is a humanized IgG1κ antibody that binds to the HGF ligand with high affinity and specificity to inhibit the biological activities of the HGF/c-Met pathway. Studies have demonstrated that ficlatuzumab is well tolerated as a single agent as well as in combination with EGFR TKIs.
About VeriStrat
VeriStrat, developed by Biodesix, is a multivariate, blood-based, protein test currently available to help physicians guide treatment decisions for patients with advanced non-small cell lung cancer. The test identifies patients who are likely to have “Good” or “Poor” outcomes after treatment with either epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy such as erlotinib or with chemotherapy. VeriStrat is based on Biodesix’ proprietary proteomics platform which enables the discovery of multivariate classifiers that characterize a patient’s condition or likely outcome in response to therapy. www.VeriStratSupport.com.
About AVEO
AVEO Oncology (NASDAQ:AVEO) is a biopharmaceutical company committed to discovering and developing targeted therapies designed to provide substantial impact in the lives of people with cancer by addressing unmet medical needs. AVEO’s proprietary Human Response Platform™ provides the company unique insights into cancer and related disease biology and is being leveraged in the discovery and clinical development of its therapeutic candidates. For more information, please visit the company’s website at www.aveooncology.com.
About Biodesix
Biodesix is a molecular diagnostics company advancing the development of innovative products for personalizing medicine. The company provides physicians with diagnostic tests for earlier disease detection, more accurate diagnosis, disease monitoring and better therapeutic guidance, which may lead to improved patient outcomes. Biodesix discovers, develops and commercializes multivariate protein diagnostics based on their proprietary mass spectrometry-based discovery platform. In addition to developing novel diagnostics independently, the company also partners with biotechnology and pharmaceutical companies to develop companion diagnostics to improve utility of therapeutic agents. For more information about Biodesix, please visit www.Biodesix.com.
SOURCE: AVEO Oncology
Post Views: 148
VeriStrat “Poor” Patients Show Encouraging Overall Survival and Progression Free Survival Signal; Confirmatory Phase 2 Study Planned by Year-End
MADRID, Spain I September 29, 2014 I AVEO Oncology (NASDAQ:AVEO) and Biodesix, Inc. today announced the presentation of results from a retrospective exploratory analysis using VeriStrat®, a commercially available serum protein test, to identify patients most likely to benefit from the addition of ficlatuzumab, AVEO’s HGF inhibitory antibody, to epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor (TKI) therapy in a randomized Phase 2 study of ficlatuzumab and gefitinib (IRESSA®) in previously untreated Asian subjects with non-small cell lung cancer (NSCLC). The results, presented in a poster session (abstract #8195) at the 2014 Congress of the European Society for Medical Oncology (ESMO), suggest that VeriStrat may be selective of positive clinical response for ficlatuzumab plus gefitinib over gefitinib alone.
“EGFR TKIs are an important class of therapy for which VeriStrat has potential prognostic and predictive value,” said Tony Mok, M.D., Professor, Department of Clinical Oncology, The Chinese University of Hong Kong, and senior investigator of the study. “VeriStrat appears to measure a host response in which tumors may become stimulated by alternative pathways, such as HGF/c-MET, leading to resistance to EGFR TKI therapy. In this exploratory analysis, the addition of the HGF-targeted antibody ficlatuzumab to an EGFR TKI therapy has shown encouraging results in this subgroup, including significant improvements in overall survival and progression free survival.”
Exploratory Analysis Results in Detail
A total of 188 patients were enrolled in a randomized Phase 2 study (P6162) designed to compare the combination of ficlatuzumab and gefitinib with gefitinib alone in treatment-naïve Asian patients with non-small cell lung adenocarcinoma. For this retrospective exploratory analysis, 180 serum samples were assigned a VeriStrat label of either “Good” (VSG) or “Poor” (VSP) (VSG=145, VSP=35). While the study failed to demonstrate improved overall survival (OS) or progression-free survival (PFS) over gefitinib alone in the intent-to-treat population, the addition of ficlatuzumab to gefitinib provided significant clinical benefit to the VSP subgroup:
| VSP |
|
ficlatuzumab and
gefitinib
n=18
|
|
gefitinib alone
n=17
|
| OS |
Median |
|
23.9 months |
|
5.8 months |
| Hazard Ratio |
|
0.41 |
| p-value |
|
0.032 |
| PFS |
Median |
|
7.4 months |
|
2.3 months |
| Hazard Ratio |
|
0.41 |
| p-value |
|
0.014 |
No benefit was observed in the VSG subgroup in either OS (Median 24.7 mo for ficlatuzumab + gefitinib [n=69] vs not reached for gefitinib alone [n=76]; HR 1.18, p=0.492) or PFS (Median 5.6 mo for ficlatuzumab + gefitinib vs 5.6 mo for gefitinib alone; HR 1.06, p=0.753). Despite the small sample sizes, similar patterns in OS and PFS based on VeriStrat stratification were also observed in patients with known EGFR mutations (n=71) and VSP classification (n=11):
| VSP and EGFRm |
|
ficlatuzumab and
gefitinib
n=5
|
|
gefitinib alone
n=6
|
| OS |
Median |
|
17.8 months |
|
10.4 months |
| Hazard Ratio |
|
0.3 |
| p-value |
|
0.09 |
| PFS |
Median |
|
11.1 months |
|
2.3 months |
| Hazard Ratio |
|
<0.01 |
| p-value |
|
<0.01 |
Based on these data, in April 2014, AVEO and Biodesix® entered into a worldwide agreement to develop and commercialize ficlatuzumab with a Biodesixcompanion diagnostic test. As part of this agreement, AVEO and Biodesix plan to conduct a confirmatory Phase 2 study using a Biodesix VeriStrat “Poor” classification as a selective biomarker for the combination of ficlatuzumab and an EGFR-TKI, versus an EGFR TKI alone, in previously untreated, EGFR mutation-positive patients with advanced non-small-cell lung cancer. The study is expected to initiate before year-end.
“This analysis suggests that VeriStrat Poor, EGFR TKI-sensitizing mutation-positive patients with NSCLC appear to have limited response to EGFR TKI alone, identifying a significant unmet medical need,” stated Tuan Ha-Ngoc, president and chief executive officer of AVEO. “Given our scientific hypothesis, and the encouraging results in this well-defined patient subset, we believe further clinical evaluation of ficlatuzumab and an EGFR TKI therapy in this population is warranted.”
“These results suggest that a blood test may be used to more precisely classify the response of a subset of patients who, based on EGFR mutation status, should be candidates for an EGFR inhibitor yet appear not to respond to the mono-therapy without the addition of ficlatuzumab,” said David Brunel, chief executive officer of Biodesix. “By using biomarkers and Biodesix’ proprietary ‘predictive intelligence’ computational approach, we believe we can further identify patient sub-populations with differential predictive and prognostic outcomes to advance decisions for therapeutic guidance. Biomarkers are empowering oncologists and the healthcare community with an evidence-based medical approach that informs more precise decisions on diagnosis, prognosis, therapeutic guidance and quality of patient care.”
A copy of the poster presentation is available on AVEO’s website at www.aveooncology.com.
About Ficlatuzumab and the HGF/c-Met Pathway
HGF is the sole ligand that binds to and activates a receptor called c-Met. Activation of the HGF/c-Met pathway is believed to be important in normal processes in embryonic development and wound healing, but its dysregulation is believed to play a role in cancer development, metastasis and drug resistance. HGF/c-Met has also been shown to be one of the most potent drivers of tumor growth in AVEO’s Human Response Platform™.
HGF/c-Met over-expression is observed in many solid tumors including breast, colorectal, gastric, head and neck, lung and prostate, as well as hematologic malignancies. Additionally, c-Met and EGFR are frequently co-amplified and co-expressed in a variety of tumor types; HGF/c-Met pathway upregulation can render resistance to EGFR-targeted therapies, and vice-versa. HGF has also been shown to be one of the most potent growth factors that can drive resistance to a panel of anti-cancer therapies.
Ficlatuzumab is a humanized IgG1κ antibody that binds to the HGF ligand with high affinity and specificity to inhibit the biological activities of the HGF/c-Met pathway. Studies have demonstrated that ficlatuzumab is well tolerated as a single agent as well as in combination with EGFR TKIs.
About VeriStrat
VeriStrat, developed by Biodesix, is a multivariate, blood-based, protein test currently available to help physicians guide treatment decisions for patients with advanced non-small cell lung cancer. The test identifies patients who are likely to have “Good” or “Poor” outcomes after treatment with either epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy such as erlotinib or with chemotherapy. VeriStrat is based on Biodesix’ proprietary proteomics platform which enables the discovery of multivariate classifiers that characterize a patient’s condition or likely outcome in response to therapy. www.VeriStratSupport.com.
About AVEO
AVEO Oncology (NASDAQ:AVEO) is a biopharmaceutical company committed to discovering and developing targeted therapies designed to provide substantial impact in the lives of people with cancer by addressing unmet medical needs. AVEO’s proprietary Human Response Platform™ provides the company unique insights into cancer and related disease biology and is being leveraged in the discovery and clinical development of its therapeutic candidates. For more information, please visit the company’s website at www.aveooncology.com.
About Biodesix
Biodesix is a molecular diagnostics company advancing the development of innovative products for personalizing medicine. The company provides physicians with diagnostic tests for earlier disease detection, more accurate diagnosis, disease monitoring and better therapeutic guidance, which may lead to improved patient outcomes. Biodesix discovers, develops and commercializes multivariate protein diagnostics based on their proprietary mass spectrometry-based discovery platform. In addition to developing novel diagnostics independently, the company also partners with biotechnology and pharmaceutical companies to develop companion diagnostics to improve utility of therapeutic agents. For more information about Biodesix, please visit www.Biodesix.com.
SOURCE: AVEO Oncology
Post Views: 148
