A Phase Ib Multiple Ascending Dose Study to Evaluate the Safety of Brivanib in Combination With 5-Fluorouracil/Leucovorin (5FU/LV) and Brivanib in Combination With 5-Fluorouracil/Leucovorin/Irinotecan (FOLFIRI) in Subjects With Advanced or Metastatic Gastrointestinal Malignancies

Inclusion Criteria:

- Histological/cytological confirmed diagnosis of Gastrointestinal malignancy, except
pancreatic cancer

- Eligible for 5FU/LV or FOLFIRI chemotherapy

- ECOG 0-1

- Able to swallow and tolerate tablets

- Life expectancy of 3 months

Exclusion Criteria:

- Unwilling to use acceptable method to avoid pregnancy of partner/self for the entire
study period and up to 4 weeks after last dose

- Women who are pregnant or breastfeeding

- Pancreatic cancer

- Known brain metastasis, evidence of leptomeningeal disease

- History of thrombo-embolic disease

- Hemorrhage/bleeding events

- Uncontrolled or significant cardiovascular disease

- Any 3 or more of the following risk factors: arterial thrombosis , smoking,
hypercholesterolemia, hypertension, obesity (BMS>30) and diabetes

- Pre-existing thyroid abnormality, not maintained with medication

- QTC (Fridericia) >450 msec on two consecutive ECG's

- Subjects with concomitant second malignancies ( except adequately treated
non-melanoma skin, in situ carcinoma of bladder, cervix or breast, early prostate
cancer)

- Any major surgery within 4 weeks of study drug administration

- Increased levels of both D-Dimer and Prothrombin fragment 1 +2

- Arm B and C only-positive UGT1A1 genotype of TA7/TA7

- History of allergy of brivanib or drug class

- History of severe reactions to fluoropyrimidine therapy or irinotecan

- Prior therapy with brivanib