13553 Background: ABT-751 (A) is an orally (PO) bioavailable sulfonamide with antimitotic properties. We are performing a non-randomized phase I/II dose-escalation study of A in combination with capecitabine (C), irinotecan (I) and bevacizumab (B) to define the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and pharmacokinetics (PK) in patients with advanced colorectal cancer (1st or 2nd line). Methods: Patients are treated with A QD for 7d (lead-in) and then begin 21-d cycles of treatment with A (QD) and C (BID) d1–14 PO, I d1 IV, and B d1 IV. Dose escalation started at dose level (DL) 1 at A 150 mg, I 200 mg/m2, and C 1600 mg/m2 (total daily dose) and escalated to full dose CAPIRI (I 250 mg/m2, and C 2000 mg/m2) for DL2. B was then added as standard of care at 7.5 mg/kg for DL2b (and later, DL1b). Blood samples were collected for pharmacogenomics (PG), pharmacodynamics (PD), steady-state PK of A and A metabolites when administered alone or in combination with C, I, and B, and PK of I and I metabolites. Serial dynamic contrast MRI’s, before and after the ABT-751 monotherapy lead-in period, are being performed in a subset of subjects. Results: Eight patients have been treated at dose levels 1 (3), 2 (2), and 2b (3). One patient on DL2 experienced g3 transaminitis and another on DL2b had F&N which were dose-limiting. Dose level 1 is being expanded to 6 patients, now with B (DL1b). Other g3/4 toxicities have included g4 neutropenia (1 subject DL2, 1 DL2b). The formation of A glucuronide appears decreased during combination therapy (see table). I PK, PD, and PG samples were collected and analysis is pending. Of 8 subjects, there have been 4 PD and 4 SD after 2 cycles. Conclusions: The combination therapy of A 150 mg and 20% dose-reduced CAPIRI appears well-tolerated. Patient accrual continues at DL1b. [Table: see text] No significant financial relationships to disclose.