Background: Ficlatuzumab is a humanized anti-HGF IgG1 MAb that inhibits activation of the c-Met receptor by neutralizing its only known natural ligand, HGF. HGF/c-Met pathway activation has been implicated in EGFR TKI resistance in NSCLC. In a phase I trial in pts with solid tumors, ficlatuzumab was well tolerated up to the maximum tested dose of 20 mg/kg both as a single agent and in combination with erlotinib (150 mg/day). Methods: Two dose levels of ficlatuzumab (10 and 20 mg/kg) in combination with 250 mg G were evaluated for safety, tolerability, and recommended phase II dose (RP2D). Enrolled pts were Asians with unresectable NSCLC, performance status (PS) ≤2, and adequate organ function. Ficlatuzumab was given IV every 2 weeks and G was given PO once daily in 28 day cycles. RP2D was defined as the highest dose at which ≤ 1 of 6 pts experienced a dose-limiting toxicity (DLT) during Cycle 1. At RP2D, 6 additional pts were enrolled. Pts were evaluated every 4 weeks for response using RECIST 1.1. Results: 15 pts enrolled: 5M/10F; median age 60 yrs, range 46-76 yrs; ECOG PS 0 (4 pts) or 1 (11 pts); median number of prior therapies was 3, range 1-5. Ten pts were EGFR TKI pretreated, 5 pts were EGFR TKI naïve. Three pts received ficlatuzumab 10 mg/kg and G 250 mg; 12 pts received ficlatuzumab 20 mg/kg and G 250 mg. No DLTs were observed in the dose-escalation cohorts. Most frequent treatment-emergent adverse events (AEs): dermatitis acneiform (53%), cough (40%), decreased appetite (33%), diarrhea (33%), paronychia (33%), edema (27%), drug hypersensitivity (27%), and fatigue (27%). Grade 3/4 related AEs: diffuse alveolar damage, paronychia, edema, and rash. RP2D is ficlatuzumab 20 mg/kg IV every 2 weeks with G 250 mg PO daily. Among 12 pts in the 20 mg/kg cohort: 5 pts had PR (all in EGFR TKI naïve), 4 had SD, and 3 had PD. Median duration of treatment: 12 weeks (range 3.6-40). Conclusions: The combination of ficlatuzumab and G was well tolerated and demonstrated clinical activity in pts with NSCLC. A phase II open-label, randomized, first line trial is ongoing in Asian pts with lung adenocarcinoma (never- or former light-smokers) comparing ficlatuzumab + G vs G alone.