Phase Ib/II study of elisidepsin in metastatic or advanced gastroesophageal cancer (IMAGE trial).

Abstract

To determine the recommended dose and antitumor activity of single-agent elisidepsin as a 24-h intravenous (i.v.) infusion fortnightly [biweekly, d1 and 15 every 4weeks (q4wk); Arm A, dose-intensity strategy] or as a 3-h i.v. infusion weekly (d1, 8, 15 and 22 q4wk; Arm B, dose-density strategy) in adult patients with unresectable, locally advanced or metastatic pretreated esophageal, gastroesophageal junction and gastric cancer. Patients were randomized to one of two elisidepsin dosing schedules. Phase Ib starting doses were 8.0mg flat dose (FD) in Arm A and 3.0mg FD in Arm B. Phase II subsequently explored antitumor activity of both dosing schedules at the respective recommended doses. Forty-four patients received elisidepsin: 12 in stage Ib and 32 in stage II. The recommended doses were defined as 10mg FD (Arm A) and 3.75mg FD (Arm B). Both schedules were well tolerated. Most adverse events were mild or moderate, reversible and predictable with no meaningful differences between schedules. The pharmacokinetic profiles of both schedules were similar to those reported previously in patients with solid tumors treated with a comparable dose. An interim analysis found tumor control in one patient receiving elisidepsin fortnightly, and in none given elisidepsin weekly; patient accrual was therefore discontinued due to lack of efficacy. Both schedules at the recommended doses presented an acceptable safety profile, but lack of response means that we do not recommend further evaluation of single-agent elisidepsin as chemotherapy for unresectable, locally advanced or metastatic gastroesophageal cancer.