111 Background: Cediranib (AZD2171) is an oral, highly potent inhibitor of VEGF signalling with activity versus all three VEGFRs and c-Kit. Combination therapy with cisplatin + oral fluoropyrimidine is commonly used as first-line treatment for AGC. This phase I study assessed cediranib in combination with cisplatin/S-1 or cisplatin/capecitabine in Japanese pts with previously untreated AGC. Methods: Eligible pts received cediranib 20 mg/day and either cisplatin 60 mg/m2 iv, day 1 + S-1 40–60 mg bd, days 1–21, q5w (Arm A) or cisplatin 80 mg/m2 iv, day 1 + capecitabine 1000 mg/m2 bd, days 1–14, q3w (Arm B). The primary endpoint was safety and tolerability. Secondary endpoints included assessment of steady-state pharmacokinetics (PK) of cediranib and chemotherapy alone and in combination. Preliminary efficacy was an exploratory objective. Adverse events (AEs) were evaluated according to CTCAE v3.0. Results: Between Aug–Dec 2009, 14 pts (median age, 60.5 [27–72] years; male, n = 9; PS 0/1, n = 7/7) were recruited to Arm A (n = 6) or Arm B (n = 8). The safety profile in both arms was consistent with that of the individual agents. There were no unexpected toxicities. All pts experienced ≥1 AE. Dose-limiting toxicities were reported in 1 pt in Arm A (decreased appetite) and 1 pt in Arm B (decreased appetite, fatigue, hyponatremia). The most common AEs in Arm A were decreased appetite, fatigue, nausea, diarrhoea, decreased weight and neutropenia (all n = 5; 83%), and decreased appetite, fatigue, nausea (all n = 8; 100%) and constipation (n = 7; 88%) in Arm B. Five (83%) pts in Arm A and 6 (75%) in Arm B experienced grade ≥ 3 AEs. Grade 3 AEs in > 1 pt were neutropenia (n = 3) in Arm A and hypokalaemia (n = 3), neutropenia, hyponatraemia and fatigue (all n = 2) in Arm B. Grade 4 syncope was reported in 1 pt in Arm A; this resolved on the same day it was observed. Preliminary efficacy and PK data will be presented. Conclusions: Cediranib 20 mg plus cisplatin/S-1 or cisplatin/capecitabine was generally well tolerated and considered suitable for further evaluation in pts with AGC. The safety profile of each regimen was comparable with the individual agents. No new toxicities were identified. [Table: see text]