Background: We sought to determine the MTD/recommended phase II (RP2D) dose of the combination of paclitaxel (P), bevacizumab (B), and temsirolimus (T) in patients (pts) with advanced solid tumors. Methods: Doses were escalated across 14 planned dose levels (DL) in a standard 3+3 design (Table). Responses were defined using RECIST 1.0. Results: To date, 61 pts have been enrolled. Four pts withdrew consent after one dose. Dose-limiting toxicities (DLTs) occurred at DL8 (G3 fatigue), DL10 (G3 hypertension, G4 pain), DL11 (G3 mucositis, G4 thrombocytopenia/neutropenia) and DL12 (G3 hyperglycemia). DL10 is being explored in expansion as the RP2D. Most common adverse events ( > 10%) were fatigue (74%; G3/4 5%), hypertriglyceridemia (49%, G3/4 5%), thrombocytopenia (38%, G3/4 7%), nausea (33%, G3/4 0%), mucositis (31%, G3/4 5%), constipation (30%, G3/4 0%), neutropenia (21%, G3/4 8%), diarrhea (20%, G3/4 0%), rash (16%, G3/4 0%), hypertension (13%, 02%), headache (10%, G3/4 2%), and vomiting (10%, G3/4 0%). Of 51pts evaluable for response, six had PR (12%) including NSCL (-64%, 13 months (m)), breast (-42%, 8m; -60% 3m), ovarian (-30%, 6m;), squamous cell cervical (-68%, +4m), and squamous cell tongue (-34%, 2m) cancer. Twenty pts (39%) had SD for 4 m or more including adenoid cystic (-3%, 10m), breast (-28%, 4m; +6%, 10m; +18%, 12m; -25%, 8m; -23%, 9m; -22%, 11m; +6%, 17m; +10%, 7m), chondrosarcoma (+8%, 19m; -19%, 6m), laryngeal/oropharyngeal (-19%, 5m; +12%, 7m), leiomyosarcoma (-10%, 38m; -10%, 8m), endometrial (-2%, 8m), gastric (-10%, 8m), ovarian (-20%, 18m) and renal (-10%, 7m) cancer. Conclusions: The combination of P, B, and T is well tolerated and demonstrates preliminary evidence of tumor activity in a variety of solid tumors, especially breast, gynecologic and squamous cancers. Studies to determine correlation of activity with tumor molecular profile are ongoing. Clinical trial information: NCT01187199

*21d cycle, ** 28d cycle