751 Background: TAS-102 is a novel oral combination therapy of FTD plus tipiracil hydrochloride (TPI) with FTD:TPI molar and weight ratios of 1:0.5 and 1:0.471, respectively. FTD is a thymidine-based nucleoside analog that has shown antitumor effects in preclinical and clinical studies. TPI stabilizes orally administered FTD by inhibiting thymidine phosphorylase and TAS-102 has shown efficacy in refractory metastatic colorectal cancer. The objective of this study was to show that TPI, administered with FTD as TAS-102, increases exposure to FTD in patients with advanced solid tumors. Methods: This is a Phase 1, randomized, open-label, pharmacokinetic study of TAS-102 in patients with advanced solid tumors. On the morning of Day 1, one group received TAS-102 35 mg/m2 and the other group received FTD 35 mg/m2. Both groups received TAS-102 35 mg/m2 on the evening of Day 1, then twice daily on Days 2-5 and 8-12 in a 28-day cycle. Blood samples were collected to evaluate FTD AUC0-last and Cmax (primary endpoints). Results: Overall, 44 patients (50% male, mean age 57 years) were treated. After a single dose, the ratio of the geometric mean of FTD AUC0-last and Cmax were 38- and 22-fold higher, respectively (Table) following TAS-102 vs FTD alone. After multiple doses (Day 12 in Cycles 1, 2, or 3), FTD AUC and Cmax were ~3- and 2-fold higher, respectively, than after a single dose of TAS-102 (Day 1). For TPI, AUC and Cmax were similar after single and multiple doses of TAS-102. After Cycle 1, FTD did not accumulate with successive cycles of TAS-102 treatment. The most commonly reported treatment-related adverse events were nausea (47.7%), fatigue (31.8%), and anemia (27.3%), with Grade 3-4 events at 4.5%, 2.3%, and 18.2%, respectively. Grade ≥ 3 decreases in neutrophil counts were observed in 42.9% of the TAS-102 group. Conclusions: TPI, in combination with FTD, substantially increased exposure to FTD vs FTD alone. Clinical trial information: NCT01867866. [Table: see text]
POS-144 A PHASE 1, OPEN-LABEL, RANDOMIZED, SINGLE-DOSE, PARALLEL GROUP SAFETY AND BIOAVAILABILITY STUDY OF BION-1301 ADMINISTERED BY INTRAVENOUS (IV) AND SUBCUTANEOUS (SC) ROUTES