E13045 Background: Tesetaxel, a novel, orally absorbed taxane that is not a substrate for P-glycoprotein, has demonstrated antitumor activity in pts with breast, gastric, and other solid tumors. Neutropenia is the most common dose-limiting effect. To date, tesetaxel has solely been administered using a once every 3 weeks schedule with an MTD of 27 mg/m2. Since other taxanes such as docetaxel and paclitaxel exhibit schedule-dependent effects, we evaluated a weekly dosing regimen of tesetaxel in escalating fixed doses. Threshold models predict taxane pharmacodynamics, and times above a threshold concentration (tC) correlate with both tumor response and toxicity; for paclitaxel, for instance, tC > 0.05 micromol/L was the best predictor of objective response and severe neutropenia (Joerger et al., Clin Cancer Res, 2007). Methods: Eligible pts had advanced solid tumors, ECOG PS 0-2, and adequate organ function. Tesetaxel was given once weekly for 3 weeks in 28-day cycles, beginning at a flat dose of 25 mg per cycle (e.g., 10 mg in Weeks 1 and 2 and 5 mg in Week 3), with progressive increase in total dose per cycle to 30, 45, 60 mg, and continued escalation in 15-mg increments to the MTD. Serial blood samples were collected, and parent compound was assayed by HPLC. Results: To date, 12 pts (3 pts/level) have been treated. Weekly dosing has been well tolerated up to 60 mg. No dose-limiting reactions have been observed, and the MTD has not been reached. Tesetaxel has a long T1/2 (~180 hrs), and low plasma concentrations in the range of 0.3–2.5 nmol/mL were detectable prior to the next dose. There was no substantial drug accumulation over multiple cycles. Conclusions: Weekly oral administration of tesetaxel is feasible and provides long-term, low-level exposure to this taxane. Given threshold effects observed with other taxanes, this finding may similarly predict clinical outcome and toxicity with tesetaxel. The MTD of this weekly regimen has not been reached, but exceeds the MTD of the every-3-week regimen.