Background: Gemcitabine (gem) with nab-paclitaxel (nab-p) is known to have antitumor activity and a favorable toxicity profile. The addition of bevacizumab (bev) to nab-paclitaxel has also been found to enhance nab-paclitaxel cytotoxicity. Methods: We therefore performed a modified 3+3 dose escalation study with 15 dose levels of fixed dose gem 1000 mg/m²IV (day 1, 8, 15) and escalating doses of nab-p IV (day 1,8, 15) and bev IV (day 1,15) every 28 days. The study design allowed for the possibility of multiple MTDs. Correlative studies on VEGF polymorphism and response were planned. (NCT01113476). Results: 103 patients (45 male) with advanced cancers were enrolled (19 ovarian, 18 pancreatic, and 18 gastroesophageal (GE) cancers among the most common). All patients were ECOG PS 0-2, median age was 60 years (range 17-85), and 51 patients (50%) were gem refractory with a median of 3 prior lines of therapy. 3 DLTs were observed during dose escalation - one with nab-p 50 mg/m² and bev 10 mg/m² (grade 3 dysphagia, dehydration), one with nab-p 75 mg/m² and bev 10 mg/m² (grade 3 cellulitis) and one with nab-p 150 mg/m² and bev 5 mg/m² (grade 3 bacteremia, hypotension). 2 DLTs were observed among the 13 patients in the nab-p 100 mg/m² and bev 5 mg/m² expansion cohort (one grade 3 diarrhea, one grade 3 fatigue) and 1 DLT among the 12 patients in the nab-p 75 mg/m² and bev 10 mg/m² expansion cohort (grade 3 rectal bleed). Dose escalation up to nab-p 125 mg/m² and bev 15 mg/m²was well tolerated with no MTD. One patient with gem refractory peritoneal papillary carcinoma achieved a complete response, 13 patients (13%) had partial responses (PR), and 54 patients (52%) had prolonged stable disease (pSD) ≥ 12 weeks. 4 patients achieving PR and 26 patients with pSD were previously gem refractory. 3/6 (50%) small cell cancers achieved PR and all 6 of these patients had tumor shrinkage of at least 25%. 4/19 (21%) ovarian cancers achieved PR, 3/18 (17%) GE cancers achieved PR, and 1/18 (6%) pancreatic cancers achieved PR. Conclusions: The combination of gem 1000 mg/m², nab-p 125 mg/m² and bev 15 mg/m² is safe, well-tolerated, and has activity even at lower doses in advanced malignancies, including gem refractory tumors. Correlative VEGF polymorphism studies are ongoing. Clinical trial information: NCT01113476