A Phase 1b Study of Oraxol in Combination with Ramucirumab in Patients with Gastric or Esophageal Cancers who failed previous chemotherapy

Date 29 September 2019
Event ESMO 2019 Congress
Session Poster Display session 2
Topics Oesophageal Cancer
Gastric Cancer
Presenter Ming Huang Chen
Citation Annals of Oncology (2019) 30 (suppl_5): v253-v324. 10.1093/annonc/mdz247
Authors M.H. Chen1, Y. Chao1, L. Tenner2, N.A. Hung3, D. Cutler4, D. Kramer4, M.R. Kwan4, C. Hung5
  • 1Deparment Of Oncology, Taipei Veterans General Hospital, 11217 - Taipei City/TW
  • 2Cancer Therapy & Research Center, University of Texas Health Science Center at San Antonio, San Antonio/US
  • 3University Of Otago, University of Otago, Dunedin/NZ
  • 4Athenex Inc, Athenex Inc, Buffalo/US
  • 5Zenith Technology Corporation Limited, Zenith Technology Corporation Limited, Dunedin/NZ

Abstract

Background

Oraxol consists of oral paclitaxel administered with the novel P-glycoprotein inhibitor HM30181A which enables the oral absorption of paclitaxel. Ramucirumab (RAM) + intravenous paclitaxel is FDA approved 2nd line treatment of gastric cancer. Oraxol 200mg/m2 days 1-3, weekly has similar exposure to weekly paclitaxel 80/m2 intravenously. This study was to determine the maximum tolerated dose (MTD) of Oraxol + RAM.

Methods

17 patients with gastric or esophageal cancers who failed prior fluoropyrimidine or platinum containing chemotherapies were studied. 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. RAM 8 mg/kg IV every 2 weeks was co-administered in all patients. Dose limiting toxicity (DLT) were assessed 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) occurred in 6 patients. Partial response (PR)=2/6, stable disease (SD)=1/6 and progressive disease (PD)=3/6. Cohort 2: One grade-3 neutropenia with treatment delay (DLT) occurred in 7 pts. PR = 3/6 and PD = 3/6 in 6 evaluable patients. Cohort 3: Two DLT (febrile neutropenia and grade-3 gastric hemorrhage) occurred in 3 patients. The MTD of Oraxol was 300mg/m2 days 1-3, weekly in combination with RAM. All patients in this study had complete recovery of their DLT. Oraxol PK did not increase significantly in Cohort-2 and Cohort-3.

Conclusions

Based on the lack of significant increase in exposure to Oraxol at higher doses, with similar efficacy and DLT in Cohorts 1 and 2, an extension study using Oraxol 200mg/m2 Days 1-3, weekly + Ramucirumab 8 mg/kg every 2 weeks as in Cohort-1 is initiated.

Clinical trial identification

NCT02970539.

Editorial acknowledgement

Legal entity responsible for the study

Athenex Inc.

Funding

Athenex Inc.

Disclosure

All authors have declared no conflicts of interest.