Phase I/II study of TH-302 in combination with gemcitabine in patients with solid tumors including advanced pancreatic cancer.

Abstract

e13519 Background: TH-302 is a 2-nitroimidazole hypoxia-activated prodrug of the DNA alkylator, bromo-isophosphoramide mustard. In preclinical models, TH-302 was active alone and enhanced the activity of gemcitabine (Gem). A phase I/II study was conducted to investigate TH-302 in combination with full dose Gem. Methods: This study used standard solid tumor eligibility criteria except patients (pts) must not have received prior Gem. Pts received IV TH-302 followed by Gem (1,000 mg/m2) on Days 1, 8 and 15 of a 28 day cycle. A standard 3+3 pts design was used with a TH-302 starting dose of 240 mg/m2. An expansion component was planned for first-line pancreatic cancer pts at the MTD. The objectives of the study were to determine the MTD/RP2D of TH-302 and Gem and to evaluate the safety, pharmacokinetics (PK) and preliminary efficacy of the combination. Results: 38 pts [20M/18F, median age: 62y (range 41-82), ECOG PS 0/1: 31/7] were enrolled at 8 sites and treated at TH-302 dose of 240 (7 pts), 340 (16), 400 (...