15532 Background: Bevacizumab is a humanized monoclonal antibody that binds to all biologically active isoforms of human vascular endothelial growth factor (VEGF). Sunitinib is a potent tyrosine kinase inhibitor of VEGFR-2, PDGFR, KIT, and FLT3. This phase I trial of bevacizumab and sunitinib was undertaken to determine the maximal tolerated dose (MTD), dose-limiting toxicity (DLT), and to evaluate for any tumor response for this novel combination. Methods: Patients (pts) with advanced solid tumors, ECOG performance status 0 or 1, and having adequate organ function were eligible. Patients received bevacizumab IV on days 1, 15, and 29 of a 42 day cycle. Sunitinib was given for 28 days with a 14 day rest. DLT was defined as any grade 4 toxicity, grade 3 cardiac event, hypertension not controlled to < 160/90 mmHg with medication, or proteinuria > 3.5 gm/24 hours. Results: Nine patients, 6 male and 3 female, with tumor types including renal carcinoma (2), bladder (2), pancreatic, testicular, melanoma, gastric, and neuroendocrine were enrolled. The median patient age was 55 years (range 37 to 83). Median number of prior systemic therapies was 2 (range 0 to 3). A total of 15 cycles have been administered (cycles range 1 to 4). Grade 1 or 2 toxicities that occurred with a > 20% incidence included anorexia, bleeding, diarrhea, dyspnea, fatigue, fever, hypomagnesemia, nausea, pain, vomiting, and weight loss. Grade 3 toxicities included hypertension (3 pts), fatigue and hypokalemia (2 pts) and one episode each of hand-foot syndrome, and hypophosphatemia. At the dose level bevacizumab 3 mg/kg and sunitnib 25 mg/day no DLTs were observed. One patient experienced DLTs of grade 4 hypertension and headache at the dose level of bevacizumab 5 mg/kg and sunitinib 37.5 mg/day. This dose level has expanded to six patients and toxicity assessment is continuing. One patient with papillary renal carcinoma has an unconfirmed partial response and three patients have experienced stable disease. Conclusions: Enrollment and toxicity evaluations are ongoing. DLTs of headache and hypertension have occurred. This trial will determine the maximal tolerated dose of this novel anti-angiogenic combination for future renal cell carcinoma studies. Supported by the NCI/Clinical Therapeutic Evaluation Program Grant U01 CA62502. No significant financial relationships to disclose.