AVEO Announces Preliminary Results of Exploratory Phase 2 Study Evaluating HGF Inhibitor in First-Line Patients with Advanced Lung Cancer
Ficlatuzumab/Gefitinib Combination Was Well-Tolerated and Demonstrated Clinical Activity; Study Results Did Not Reach Statistical Significance
Encouraging Signals of Anti-tumor Activity in Distinct Subpopulations
“Some patients with EGFR sensitizing mutations do not respond well to
EGFR TKI therapy,” stated
The primary endpoint of the study was overall response rate (ORR), and progression free survival (PFS) was a secondary endpoint. Preliminary results in the intent-to-treat (ITT) population (n=94 each arm) showed a trend favoring the ficlatuzumab/gefitinib combination; however, as with data from Phase 2 studies in NSCLC with other inhibitors of the Met pathway, study results in the ITT population did not reach statistical significance. In the ITT population, ORR was 43% for the ficlatuzumab/gefitinib combination arm versus 40% for the gefitinib monotherapy arm, and median PFS was 5.6 months versus 4.7 months for the ficlatuzumab/gefitinib combination arm versus the gefitinib monotherapy arm, respectively, favoring the combination arm.
Encouraging signals of activity were observed in biomarker subset populations. Key findings are summarized in the following chart:
|Ficlatuzumab/Gefitinib Combination||Gefitinib Alone|
|EGFR SM+/c-Met Low||10||11.0||70||9||5.5||44|
|EGFR SM+/c-Met High||23||9.2||52||27||9.2||63|
|EGFR SM-/c-Met Low||9||1.3||0||13||2.3||0|
|EGFR SM-/c-Met High||11||1.8||27||16||1.8||13|
No clinically meaningful differences in adverse event rates between the combination and monotherapy arms were observed, and the combination was well-tolerated. Complete data from this trial, which will include biomarker analyses, are anticipated to be submitted for presentation at an upcoming medical meeting in the second half of this year.
“These are important data for driving our ficlatuzumab program forward,
as well as for demonstrating the clinical value of AVEO’s proprietary
Human Response Platform,” stated
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, respectively; 144 tumor tissue samples were available for biomarker analysis. Subjects who demonstrated disease control (complete response, partial response, or stable disease for 12 weeks or longer) in the gefitinib alone arm were eligible to cross-over upon progression to a 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 a 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 is also believed to trigger many activities involved in cancer development and metastasis. HGF/c-Met has 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 malignancies1. 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 EGFR-targeted therapy resistance, and vice-versa2-4.
Ficlatuzumab is a humanized IgG1 antibody that binds to the HGF ligand with high affinity and specificity to inhibit the biological activities of the HGF/c-Met pathway.
Cautionary Note Regarding Forward-Looking Statements
Any statements in this press release about AVEO’s future
expectations, plans and prospects, including statements about: the
potential efficacy and safety of ficlatuzumab; advancement of the
ficlatuzumab clinical development plans in lung cancer and head and neck
cancer; ficlatuzumab’s therapeutic potential in combination with EGFR
targeted therapies; the potential of AVEO’s cancer biology platform and
biomarker capabilities 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 Annual
Report on Form 10-K filed with the
1. Christensen JG, et al. Cancer Letters: 225:1-26.
2. Engelman JA, et al. Science. 316:1039-43.
4. Yano S, et al. Cancer Res. 68:9479-87.
Monique Allaire, 617-299-5810
Rob Kloppenburg, 617-930-5595
Dan Budwick, 973-271-6085