Background: PICN is a novel Cremaphor-free composite of paclitaxel nano-particles stabilized with polymer and lipid using NanotectonTechnology. PICN started development with every-3-week schedule of PICN +/- carboplatin (ASCO 2013; #2557). This study aimed to determine the maximum tolerated dose (MTD) and pharmacokinetic (PK) profile of PICN dosed using a weekly schedule. Methods: Patients (pt) with solid malignancies and ECOG PS 0-1 were eligible, and the dose escalation was conducted per a ‘3+3’ design. PICN was administered i.v. weekly for 3 weeks then1 week rest (28 days per cycle) at planned dose levels 80, 100, 125 and 150 mg/m². The 125 mg/m²level was intolerable in pts who previously received multiple lines of chemotherapy (Arm A), and the study was amended to continue dose escalation in pts who previously received 2 or less lines of treatment (Arm B). Only standard anti-emetic pre-medications were used. Adverse events (AEs) were graded using CTCAE 4.0 and tumor response by RECIST 1.1 Results: A total of 22 pts were enrolled from 2 US academic centers and 15 evaluable for dose limiting toxicity (DLT). Number of pts at each level were n=3 at 80, n=6 at 100, n=3 at 125 (Arm A) and n=3 at 125 mg/m² (Arm B). The DLTs observed were: dose delay for > 7 days for Gr1 ANC at 100 mg/m²; Gr3 fatigue and Gr3 weakness at 125 mg/m² (Arm A). Anti-tumor efficacy was observed in breast (PR, 80 mg/m²), ovarian (SD for > 12 months; 100 mg/m²), and urothelial (PR; 125 mg/m²) cancers. Previous treatments received in the ovarian pt included platinum(P)/paclitaxel, P/docetaxel and P/gemcitabine; and, P/gemcitabine in the urothelial pt. The dose level of 125 mg/m²(Arm B) was tolerable and enrollment to higher dose levels are underway. PK analysis showed dose-proportional increase in total plasma paclitaxel level. Conclusions: When administered on a weekly schedule (3-weeks-on/1-week-off), 100 mg/m² was the MTD in heavily pretreated pts. 125 mg/m² was tolerable in pts who received 2 or less previous lines of chemotherapy. Anti-tumor efficacy was observed in breast, ovarian and urothelial cancers. Final PK, toxicity and efficacy data will be reported at the conference. Clinical trial information: NCT01305512.