AVEO Announces Detailed Results of Exploratory Phase 2 Study Evaluating Ficlatuzumab in First-Line Patients with Advanced Non-small Cell Lung Cancer; New Data Presented at ESMO
Ficlatuzumab Phase 1 Pharmacodynamic Data Also Presented
“The insights gleaned from the Phase 2 study, along with new
pharmacodynamic data, show that inhibiting the HGF ligand may be
important in the treatment of cancer,” stated
“This study has identified potential predictive biomarkers for the use
of ficlatuzumab in patients with advanced NSCLC,” said
The primary endpoint of the study was overall response rate (ORR); secondary endpoints included progression-free survival (PFS), overall survival (OS) and correlation of biomarkers with clinical activity. In the intent to treat (ITT) population, the addition of ficlatuzumab to gefitinib did not result in statistically significant improved ORR or PFS in Asian treatment-naïve NSCLC patients. The preliminary OS hazard ratio in the ITT population for ficlatuzumab plus gefitinib versus gefitinib monotherapy was 0.84 (95% CI 0.52, 1.37). Final OS data will be presented once they are mature. The combination was well-tolerated, with no clinically meaningful differences in adverse event rates observed between the two arms.
The combination demonstrated a trend for improved ORR and PFS in patients with both EGFR-sensitizing mutations and low c-Met biomarker levels (n=19).
Preliminary OS results suggest that the addition of ficlatuzumab to gefitinib may have a favorable impact in the subset of patients with high stromal HGF (N=17 patients, HR=0, p=0.03). Trends for OS benefit in other biomarker subsets continue to be evaluated.
Results from a Phase 1 clinical study evaluating tumor pharmacodynamic changes post ficlatuzumab treatment were also presented at ESMO. In the majority of patients treated, 20 mg/kg of ficlatuzumab (the established Phase 2 dose of ficlatuzumab) resulted in pharmacodynamic modulation in liver metastasis by inhibiting the HGF/c-Met pathway and downstream signaling for cell proliferation, survival, and angiogenesis.
Exploratory Phase 2 Study Overview
The open-label, two-arm, randomized exploratory Phase 2 study was designed to compare the combination of ficlatuzumab and gefitinib versus gefitinib monotherapy, in clinically selected Asian subjects with previously untreated advanced NSCLC who have a high likelihood of harboring activating EGFR mutations. Ninety-four (94) patients were randomized to gefitinib and ficlatuzumab/gefitinib arms each; 144 tumor tissue samples were collected for biomarker analysis. Subjects who demonstrated disease control (complete response, partial response, or stable disease for 12 weeks or longer) in the gefitinib arm were eligible to cross-over upon progression to the combination of gefitinib and ficlatuzumab, to assess whether acquired resistance to gefitinib can be overcome with the addition of ficlatuzumab.
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.
AVEO Oncology (NASDAQ: AVEO) is a cancer therapeutics company committed to discovering, developing and commercializing targeted therapies to impact patients’ lives. AVEO’s proprietary Human Response Platform™ provides the company unique insights into cancer biology and is being leveraged in the discovery and clinical development of its cancer therapeutics. For more information, please visit the company’s website at www.aveooncology.com.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements that involve
substantial risks and uncertainties. Any statements in this press
release about AVEO’s future expectations, plans and prospects, including
statements about: the potential efficacy and safety of ficlatuzumab;
inhibition of the HGF ligand potentially being important in the
treatment of cancer, advancement of the ficlatuzumab clinical
development plans in lung cancer; and the registration process for
tivozanib; ficlatuzumab’s therapeutic potential in combination with EGFR
targeted therapies, particularly in the subset of patients with high
stromal HGF; the potential of AVEO’s cancer biology platform to offer a
unique advantage in oncology drug development; and other statements
containing the words "believes," "anticipates," "plans," "expects,"
“potential,” "will" and similar expressions, constitute forward-looking
statements within the meaning of The Private Securities Litigation
Reform Act of 1995. Actual results may differ materially from those
indicated by such forward-looking statements as a result of various
important factors, including risks relating to: AVEO’s ability to
successfully research, develop and obtain and maintain regulatory
approvals for ficlatuzumab and its other product candidates, including
risks relating to its ability to successfully advance clinical
development of ficlatuzumab for the treatment of lung cancer; the
possibility that favorable historical preclinical and clinical trial
results may not be predictive of the results in future preclinical and
clinical trials; AVEO’s ability to obtain and maintain adequate
protection for intellectual property rights relating to its product
candidates and technologies; unplanned operating expenses; AVEO’s
ability to raise substantial additional funds to achieve its goals,
including with respect to the further development of ficlatuzumab;
competition; general economic and industry conditions; and other factors
discussed in the "Risk Factors" section of AVEO’s Quarterly Report on
Form 10-Q filed with the
Source: AVEO Oncology
Monique Allaire, 617-299-5810
Rob Kloppenburg, 617-930-5595
Dan Budwick, 973-271-6085