Phase Ib/Ii Study Of Cancer Stem Cell (Csc) Inhibitor Bbi608 Combined With Paclitaxel In Advanced Gastric And Gastroesophageal Junction (Gej) Adenocarcinoma.

4069 Background: BBI608, a first-in-class CSC inhibitor that works through inhibiting Stat3, has shown potent synergistic anti-tumor and anti-metastatic activity with paclitaxel in vivo. In a phase Ib dose escalation study in patients with advanced solid tumors, BBI608 + weekly paclitaxel was well tolerated and a RP2D of BBI608 500 mg BID was determined. Methods: Patients with advanced, pre-treated gastric and GEJ adenocarcinoma were enrolled in a phase Ib/II extension study to assess safety, tolerability, and preliminary anti-cancer activity in patients with advanced gastric/GEJ adenocarcinoma. Eligible patients received ≥ 1 line of prior treatment in the metastatic setting with a platinum + fluoropyrimidine/TS inhibitor. BBI608 was administered orally at 480 mg or 500 mg twice daily with paclitaxel 80 mg/m2 IV weekly 3 of every 4 weeks. A sample size of 40 set the bounds of the 90% CI at ±10% to 14%, assuming a DCR of 60% to 80%. Results: 46 patients (87% Caucasian, 7% Black, 6% Asian) were enrolled in ...