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 OverviewThe 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™.