Background: Combined mTOR and VEGF blockade is a potentially promising and rational strategy for the treatment of advanced RCC. We previously reported the phase I safety and initial efficacy results of temsirolimus (T) +bevacizumab (B) in RTKI naïve stage IV RCC patients (pts) (J Clin Oncol 2007, 25(18S Suppl):5034). We now report the final results of the phase II study of T+B in RCC patients (pts) previously treated with VEGFR TKI. Methods: Design: Open label, phase I/II study of T+B in advanced RCC pts. Pts with measurable stage IV RCC with a component of clear/conventional cell type, performance status 0-2 and good organ function were eligible. Up to two prior treatment regimens were allowed (at least one prior RTKI). Phase II dose was T=25 mg IV weekly and B= 10 mg/kg every 2 weeks repeated in 4 week cycles. The primary objective (phase II portion): to assess the proportion of patients who were progression-free 6 months after study entry. Secondary objectives: assessment of response rates and toxicity. Results: Forty-six pts have been enrolled into the phase II portion (5 ineligible pts; 1 pt cancelled prior to starting treatment). Forty pts are evaluable for response assessment and 45 pts are evaluable for toxicity. Baseline characteristics (N: 46): median age: 62 (38-82); M/F: 35/11; number of met. sites: 1/2/3+: 19/9/18; prior nephrectomy: 42; number of prior RTKIs: 1= 40; 2=3. Most common (>5%) Gr 3-4 AEs (N=45) included fatigue (17.8%), hypertriglyceridemia (11.1%), stomatitis (8.9%), proteinuria (8.9%), abdominal pain (6.7%), and anemia (6.7%). Best responses were: PR/SD/PD= 9(23%)/25(63%)/6(14%). Six-month progression free rate: 40% (16/40 pts). Median time to progression: 7.6 (4-8.5) months. Median overall survival: 20.6 (11.5-23.7) months. Conclusions: T+B combination at the recommended phase II doses is feasible and active in RTKI treated RCC patients. The 6 month progression-free rate (40%) met the efficacy endpoint and warrants confirmatory studies for clinical activity. Correlative studies on available plasma, serum and tumor samples for angiogenic and molecular biomarkers are underway. Support: N01-CM62205, CA 119545-02, and Commonwealth Foundation.