205P - Efficacy Analysis of Gefitinib +/- Ficlatuzumab in Serum Proteomic Based Subgroups of Patients with Previously Untreated Lung Adenocarcinoma

Abstract

ABSTRACT Aim: Ficlatuzumab (F), a humanized anti-hepatocyte growth factor (HGF) IgG1 mAb, inhibits c-MET receptor activation by neutralizing HGF. HGF/c-MET pathway activation has been implicated in epithelial growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance in non-small cell lung cancer. A randomized Phase 2 study of gefitinib (G) +/- F in Asian patients with previously untreated lung adenocarcinoma (±EGFR mutations) failed to demonstrate improved overall survival (OS) or progression-free survival (PFS) over G alone (NCT01039948) in the intent-to-treat population. VeriStrat® (VS) is a multivariate serum proteomic test that utilizes mass spectrometry to assign a “GOOD” (VSG) or “POOR” (VSP) classification and has demonstrated broad prognostic and predictive utility for EGFR TKI treatments. In part, VS appears to measure a host inflammatory state that may stimulate tumors via alternative pathways, including HGF secretion. Methods: 183 blinded unique patient pretreatment serum samples from the study were sent for VS analysis. Clinical outcomes of F + G vs G alone were analyzed in VS subgroups. Results: 183 serum samples were assigned a VS label (VSG = 145, VSP = 35, and 3 “Indeterminate”). Addition of F to G provided significant clinical benefit to the VSP subgroup: OS hazard ratio (HR) 0.41, P = .032; medians = 23.9 mo for F + G (N = 18) vs 5.8 mo for G alone (N = 17) and PFS HR 0.41, P = .014; medians = 7.4 mo for F + G vs 2.3 mo for G alone. No benefit was observed in the VSG subgroup in either OS (HR 1.18, P = .492; median 24.7 mo for F + G [N = 69] vs not reached for G alone [N = 76]) or PFS (HR 1.06, P = .753; median 5.6 mo for F + G vs 5.6 mo for G alone). Unadjusted interaction test for treatment and VS was statistically significant for OS (HR = 3.31, P = .013) and PFS (HR = 2.51, P = .019). Despite the small sample sizes, similar patterns in OS and PFS based on VS stratification were also observed in patients with known EGFR mutations (n = 71). Conclusions: VS may be predictive for clinical benefit of F + G over G (OS and PFS) in patients classified as VSP. A prospective confirmatory study using VS as predictive biomarker on the combination of F + EGFR-TKI in EGFR mutation–positive patients is planned. Disclosure: J.C. Yang: Advisory boards: Boehringer Ingelheim, Eli Lilly, Pfizer, Novartis, Roche/Genetech, Astrazeneca, Merck, Bayer, Clovis Oncology Corporate sponsored research: Boehringer Ingelheim; J. Gyuris, M.Han, F. Payumo and Z. Weng have declared: AVEO Oncology employee • Stock • Salary; P. Komarnitsky: (former) AVEO Oncology employee; G. Pestano, J. Roder and D. Spinella have declared: Biodesix employee • Stock • Salary; K. Park: Advisory boards: AVEO, Astellas, AZ, BI, Clovis, Daiichi Sankyo, Eli Lilly, Kyowa Hakko Kirin, Novartis, Roche. All other authors have declared no conflicts of interest.