6592 Background: VEGF is overexpressed in a number of malignancies. We previously found high expression of VEGF and its receptors in a sample of aggressive NHL specimens. Based on these results, we initiated this trial. Methods: Patients (pts) were treated every 2 weeks with bevacizumab (BV), a recombinant monoclonal antibody against VEGF, at a dose of 10mg/kg IV. Eligibility was limited to advanced stage aggressive NHL histologies in 1st or 2nd relapse. Results: 51 pts were registered (5 ineligible). Median age was 70 yrs (range: 36–87). 44 pts have been evaluated for toxicity. One died of pulmonary emboli and another died of probable progressive disease (possible causal relationship to drug could not be ruled out). 15 pts had grade 3 toxicities. The most common were cytopenias (10); fatigue, malaise, or lethargy (5); dyspnea (3); hypertension (2); hyponatremia (2); and dehydration (2). 40 eligible pts were evaluated for best response. There were 2 PR for an overall response rate of 5% (95% C.I. 1–17%). Eight pts had SD as their best response. The non-progression rate (PR + SD) was 25%. The median TTP was 5 months, range 4–18 months, in non-progressing pts. In all pts, 6-month PFS estimate was 14% (95% C.I.: 4–24%). The 6-month OS was 58% (95% C.I.: 43–73%). IHC was performed on diagnostic tumor for VEGF and its receptors. 19 samples were adequate for analysis with 14 (74%) expressing VEGF and 13 expressing one or both receptors. Additional studies included baseline, week 8, and at-time-of-progression measurements of circulating endothelial cells (CEC), and plasma and urine angiogenic markers (VEGF, VCAM, and bFGF). Over the course of therapy, CEC (p=.12) and plasma VEGF (p<.001) levels decreased while plasma VCAM (p=.02) levels increased. Conclusions: Therapy with BV was well-tolerated in this pre-treated group of pts with prolonged stabilization of disease seen in a small, but significant subset. The high rate of concordance between expression of VEGF and receptors suggests an autocrine pathway may play an important role in NHL pathogenesis. These results provide a strong rationale for studying the addition of BV to standard chemotherapy in the treatment of aggressive NHL. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech