Addition of ficlatuzumab to gefitinib may be effective in select subsets of patients with NSCLC

AVEO Oncology (NASDAQ: AVEO) today announced that detailed results from an exploratory, randomized Phase 2 study evaluating the combination of ficlatuzumab, the company's HGF inhibitory antibody, and gefitinib compared to gefitinib monotherapy in previously untreated Asian subjects with non-small cell lung cancer (NSCLC) were presented at the 2012 Congress of the European Society for Medical Oncology (ESMO). As previously reported, the study did not achieve its primary endpoint; however, the results presented at ESMO suggest that the addition of ficlatuzumab to gefitinib may be effective in select subsets of patients.    

"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 Tuan Ha-Ngoc, president and chief executive officer, AVEO. "We, along with our scientific advisors and clinical investigators, remain encouraged about ficlatuzumab and believe the program warrants further evaluation. Our top priority is the registration and commercialization of tivozanib, and with that in mind, we will be focusing our efforts on further ficlatuzumab development through external collaborations, including with academic institutions and cooperative groups."

"This study has identified potential predictive biomarkers for the use of ficlatuzumab in patients with advanced NSCLC," said Tony Mok, M.D., professor, Department of Clinical Oncology, The Chinese University of Hong Kong, and senior investigator of the study. "Based on these results, ficlatuzumab merits additional clinical investigation."

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.    

Source: AVEO Oncology