E14119 Background: PDGFR inhibition by reducing tumoral interstitial fluid pressure may increase chemotherapy penetration and efficacy. Imatinib (IM) has anti-PDGFR activity at standard doses. The aims of this phase I study were to assess the MTD of IM in combination with mFOLFOX-bevacizumab (Bev) in patients (pts) with advanced colorectal cancer (CRC), identify potential PK interactions, toxicities and efficacy. Methods: Eligible pts had measurable disease, 0-1 prior regimens, ECOG 0-1, adequate organ function. On day -14, pts commenced IM p.o daily + Bev (5mg/kg/2 weekly). On day 1, (14 days post), pts commenced mFOLFOX-Bev (oxaliplatin 85mg/m2/2hrs, leucovorin 200mg/m2, 5FU bolus 400mg/m2 day 1, 5FU CI 2.4g/m2/46hrs). Bloods were taken for IM steady state PK analysis from day -14 to day 14; and for oxaliplatin and 5FU PK in cycle 1, days 1 to 3. DLTs were defined, in the first 6 weeks, as: grade (Gr) 4 neutropenia >7 days, Gr4 thrombocytopenia/Gr3 with bleeding, febrile neutropenia, drug-related Gr3/4 non-haematological toxicity, delay in the start of next cycle >2 weeks. Dose escalation was standard with 3 pt cohorts. IM planned dose levels (DL): DL1; 400mg, DL2; 600mg, DL3; 800mg po daily. Pts restaged on day 1 cycles 1 and 2 and then every 8 weeks. Results: 10 pts enrolled, M:F = 7:3, 1 pt had prior chemotherapy. DL1; 3 pts, DL2; 7 pts (1 replaced due to early progression). DLTs observed in 3 of 6 pts in DL2 (600mg): febrile neutropenia (2); Gr3 infection and Gr4 neutropenia (1). Worst drug-related AEs: DL1 (3); Gr3 thromboembolism (1), Gr3 hypertension (1), Gr4 neutropenia (1). DL2 (7); febrile neutropenia (2), Gr4 dehydration (1), Gr3 (4) and Gr4 (1) neutropenia. Median number of cycles: DL1 = 12, DL2 = 6 (range 1-12). Overall response rate: DL1 = 1/3 (SD 2/3), DL2 = 0/6 (SD 5/7). Steady state PK parameters for IM were not impacted by mFOLFOX-Bev. Oxaliplatin and 5FU PK parameters were not impacted by IM exposure. Conclusions: 400mg p.o. daily of IM was the MTD with mFOLFOX-Bev. Dose escalation of IM an inhibitor of PDGFR, ABL and KIT was limited by neutropenia. Further study is warranted as IM can be delivered at levels that inhibit PDGFR.