2019 ASCO Annual Meeting!
Session: Gastrointestinal (Noncolorectal) Cancer
Type: Poster Session
Time: Monday June 3, 8:00 AM to 11:00 AM
Location: Hall A
NUC-1031 in combination with cisplatin for first-line treatment of advanced biliary tract cancer.
Gastrointestinal (Noncolorectal) Cancer
2019 ASCO Annual Meeting
Poster Board Number:
Poster Session (Board #253b)
J Clin Oncol 37, 2019 (suppl; abstr TPS4156)
Author(s): Jennifer J. Knox, Mairead Geraldine McNamara, Daniel H. Palmer, T.R. Jeffry Evans, David Goldstein, John A. Bridgewater, Juan W. Valle; Princess Margaret Cancer Centre, Toronto, ON, Canada; University of Liverpool, Liverpool, United Kingdom; University of Glasgow, Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom; Prince of Wales Hospital, University of New South Wales, Cancer Survivors Centre, Randwick, Australia; University College London Cancer Institute, London, United Kingdom; University of Manchester/The Christie, Manchester, United Kingdom
Background: Cisplatin and gemcitabine (CisGem) is the global standard of care for 1st-line treatment of patients (pts) with advanced biliary tract cancer (BTC). No agents have regulatory approval for this disease. CisGem achieves an objective response rate (ORR) of 26% and median overall survival (OS) of 11.7 months (ABC-02). Key cancer resistance mechanisms limit gemcitabine efficacy. NUC-1031, a phosphoramidate transformation of gemcitabine, is designed to overcome resistance mechanisms associated with poor gemcitabine response. Promising signs of efficacy have been observed with single agent in a phase I study in solid tumors (Blagden et al 2018) and in the phase Ib ABC-08 study of NUC-1031 + cisplatin 25 mg /m2 d1, d8 q 21 days for the 1st-line treatment of advanced BTC. 14 pts have been enrolled across 2 cohorts (NUC-1031: 625 mg/m2 and 725 mg/m2). In 11 pts evaluable for response ORR was 64% (1 CR, 6 PRs) and DCR was 73%. PFS/OS data is maturing. The combination was very well-tolerated with no unexpected adverse events or dose-limiting toxicities. The RP2D in combination with cisplatin is 725 mg/ m2. Safety, coupled with encouraging efficacy signal has led to initiation of a global Phase III development program. Methods: A Phase III, open-label, randomized head-to-head study of NUC-1031 + cisplatin versus CisGem for the 1st-line treatment of advanced BTC will include pts ≥18 years with histologically- or cytologically-proven BTC (including cholangiocarcinoma, gallbladder, or ampullary cancer), that is not resectable and who have had no prior systemic chemotherapy for locally advanced/metastatic disease. A total of 828 pts will be randomized (1:1) to either 725 mg/m2 NUC-1031 + 25 mg/m2 cisplatin or 1000 mg/m2 gemcitabine + 25 mg/m2 cisplatin, administered on Days 1 and 8 of a 21-day cycle, respectively. Primary objectives are OS and ORR. Secondary objectives include further measurements of efficacy, safety, pharmacokinetics, and patient-reported quality of life. The study will be conducted at approximately 120 sites across North America, Europe and Asia Pacific countries. Clinical trial information: NCT02351765