First-line treatment with bevacizumab (B) and high dose (HD) bolus aldesleukin (IL-2) in metastatic renal cell carcinoma (mRCC) patients (Pts)

15524 Background: The rationale for combining HD IL-2 with B includes potential synergistic immune interactions, non-overlapping toxicities, and potential for added clinical benefit. We have initiated a multi-center phase II study designed to estimate the efficacy of combination therapy of standard HD IL-2 and B therapy in mRCC pts. Methods: Pts with histologically confirmed mRCC, predominantly clear cell histology, measurable or evaluable disease, KPS of =80%, adequate end organ function for HD IL-2, and no underlying coagulopathy or thrombotic event are eligible for this study. One cycle consists of 84 days. B (10 mg/kg) IV is given every 2 wks beginning 2 wks prior to the first dose of IL-2. B is dosed 1 hr prior to initiating IL-2 on days IL-2 is given. HD IL-2 (600,000 IU/kg) IV Q8 hours (maximum 28 doses) is given during two 5-day courses separated by 9 days (starting on day 15 and 29). Results: We report the results of the first 15 of a planned 60 pts. The median age is 54 (range 40–73) with 9 men and 6 women. 14 pts have a MSKCC intermediate prognostic score, one pt has a poor prognostic score. In the first cycle, the median number of B doses was 7 of a planned 7 (range 2–7) and the median number of IL-2 doses was 17 of a planned 28 (range 6–26). There has been one treatment related death from unresponsive hypotension which occurred during the second cycle. Typical IL-2 toxicities have been noted thus far. Among a variety of correlative studies, we evaluated the serum L- ornithine (L-O) level, a byproduct of arginase-mediated arginine metabolism that has been shown to inversely correlate with TCR? chain expression. L-O level are significantly elevated in RCC pts possibly due to VEGF stimulation of arginase production. In 4 patients tested to date, peripheral blood L-O levels have dramatically decreased over the course of therapy. Conclusions: HD IL-2 and B can be given safely and may impact on immune regulatory pathways. [Table: see text]