2575 Background: TPI 287 is an investigational taxane designed to not be a substrate for mdr-1 and to bind to mutant tubulin. In preclinical studies, TPI 287 demonstrated activity against multiple human tumor xenografts in nude mice, including xenografts that expressed mdr-1 and that were resistant to other taxanes. The safety and tolerability of TPI 287 when administered weekly for 3 weeks followed by a 1 week rest (4 week cycle) was examined in this Phase 1 dose escalation study in patients (pts) with advanced neoplasms. Materials and Methods: TPI 287 was administered over 1 hour weekly for 3 weeks followed by 1 week of no treatment. Treatment cohorts consisted of 3 pts and were expanded to 6 pts in the face of dose-limiting toxicity (DLT); pts could remain on study until the development of progressive disease or an intolerable adverse event. DLT was defined as Gr 4 heme toxicity lasting 7 days; febrile neutropenia, Gr 3 thrombocytopenia with bleeding, Gr 3 elevation of transaminases lasting 7 days or any other Gr 3/4 toxicity other than nausea or vomiting. Results: 25 pts (M:F 16:9, median age 60, range 24 - 86) were enrolled in 7 dose levels ranging from 7–185 mg/m2. Pts’ cancers included colorectal (6 pts); NSCLC (2); prostate (2); squamous cell carcinoma (2) and 1 pt each with cervical, breast, ovarian, gastric, pancreatic, bladder endometrial, NSCLC, SCLC, glioblastoma, melanoma, renal cell and hepatocellular carcinoma. All pts but 1 had received prior chemotherapy (median no. prior treatments: 3 (range, 1–7). Drug related adverse events included nausea, vomiting, diarrhea, fatigue, anorexia, rash, anemia and peripheral neuropathy. 1 pt., who was inadvertently treated with inadequate marrow reserve, experienced Gr 4 neutropenia and died of sepsis. DLT of Grade 3 peripheral neuropathy has been observed. PK data to date reveal that AUC is generally dose linear. At a dose of 127.5 mg/m2, clearance was 30.2 + 11.9 L/hr/m2 and t1/2 8.6 + 1.3 hrs. Results are similar with non-compartmental methods and 2-compartment modeling. Conclusions: TPI 287 can be safely administered in doses of up to 127.5 mg/m2 weekly x 3. No significant financial relationships to disclose.