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3556 Background: Aflibercept (AF) is a recombinant fusion protein that is a potent inhibitor of vascular endothelial growth factor (VEGF). This study was designed to assess the safety/tolerability, dose-limiting toxicities (DLTs), recommended Phase II dose, and PK of AF + FOLFOX4. Methods: This combination trial explored escalating iv doses of AF followed by standard fixed FOLFOX4 regimen, every 2 weeks. Results: 32 pts (M/F 9/23, median age 59 25–79, ECOG-PS 0/1: 11/21) were enrolled in 3 AF dose levels: 2.0 (n = 4), 4.0 (n = 18) and 5.0 (n = 10) mg/kg. Primary tumors were mostly gastro-intestinal (16, including 8 pancreas, 3 cholangiocarcinoma and 3 gastric), breast (5), ovarian (4), and others (7). Most (75%) pts were heavily pre-treated, with a median number of prior lines of 31–9. Pts received a median number of 4.5 1–20 treatment cycles (cy). During the dose escalation phase, no AF-related DLT (first 2 cy) was observed. Gr > 3 NCI-CTCAE v3.0 toxicity observed included: neutropenia (69%), thrombocytopenia (13%), hypertension (13%), proteinuria (13%), hemorrhagic events (9%, including one G5 hemorrhagic stroke at 4 mg/kg), febrile neutropenia (3%), deep vein thrombosis (3%). A G5 posterior leukoencephalopathy syndrome was reported at 5 mg/kg. Five partial responses were noted (pancreas, cholangiocarcinoma, colo-rectal; all at doses > 4 mg/kg) and 10 pts had stable disease. Free and bound AF drug concentrations in combination with FOLFOX4 are comparable to those observed with AF as monotherapy. At doses > 4 mg/kg, free AF exceeds bound AF over the dosing interval, suggesting sustained effective trapping of VEGF. Conclusions: AF 4 mg/kg combined with FOLFOX4 was selected for further investigations, based on activity, overall safety profile (consistent with that of other agents from the same class), and PK. Updated data will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration sanofi-aventis sanofi-aventis sanofi-aventis
Limentani et al. (Tue,) studied this question.