A phase Ib study of oraxol in combination with ramucirumab in patients with gastric or esophageal cancers who failed previous chemotherapy

e15518 Background: Oraxol consists of oral paclitaxel (PTX) administered with the novel P-glycoprotein inhibitor HM30181A which enables the oral absorption of PTX. Ramucirumab (RAM) + intravenous weekly PTX is FDA approved 2nd line treatment of gastric cancer. Oraxol (oral PTX) 200mg/m2 days 1-3, weekly results in similar exposure to weekly 80/m2 intravenous PTX. This phase 1 clinical trial is to determine the maximum tolerated dose (MTD) of Oraxol + RAM. Methods: Eligible patients (pts) have gastric or esophageal cancers and failed prior fluoropyrimidine or platinum containing chemotherapies. Dose escalation followed the standard 3+3 design: Cohort 1: Oraxol 200mg/m2 days 1-3, weekly. Cohort 2: Oraxol 250mg/m2 days 1-3, weekly. Cohort 3: Oraxol 300mg/m2 days 1-3, weekly. Dose of RAM is standard 8 mg/kg IV every 2 weeks. Pts were monitored for dose limiting toxicity (DLT) by week 4. Adverse events (AEs) were assessed per CTCAE v4.03 and response by RECIST v1.1. Results: Cohort 1: One febrile neutropenia (DLT) observed in 6 pts. Partial response (PR) = 2/6, stable disease (SD) = 1/6 and progressive disease (PD) = 3/6 pts. Cohort 2: One grade-3 neutropenia with treatment delay (DLT) in 7 pts. PR = 3/6 and PD = 3/6 in 6 evaluable pts. Cohort 3: One febrile neutropenia (DLT) in 3 pts and study is ongoing. All pts had complete recovery of their DLT. PK showed increase of plasma PTX exposure with dose. Conclusions: The MTD for Oraxol has not been reached yet in combination with RAM. Preliminary results showed that Oraxol + RAM is tolerable and have encouraging anti-tumor activity in gastric or esophageal cancers pts who failed prior chemotherapies. Final results of this study will be presented. Clinical trial information: NCT02970539.