A randomized, double-blind, placebo-controlled study of ibrutinib, a Bruton tyrosine kinase inhibitor, with nab-paclitaxel and gemcitabine in the first-line treatment of patients with metastatic pancreatic adenocarcinoma (RESOLVE).

Abstract

TPS2601Background: Advanced pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor prognosis and short survival. Nab-paclitaxel/gemcitabine (Nab-P/GCB) is a preferred front-line treatment regimen. The Bruton tyrosine kinase (BTK) inhibitor ibrutinib (ibr) demonstrates antitumor activity in preclinical PDAC models, due in part to modulation of the tumor microenvironment. Ibr treatment inhibits mast-cell degranulation and decreases tumor-associated inflammation and desmoplasia; simultaneously, ibrutinib enhances the presence and activity of cytotoxic T cells in tumors (Affara et al, Cancer Cell, 2014; Masso-Valles et al, Cancer Res, 2015; Gunderson et al, Cancer Discov, 2015). This study will evaluate the efficacy of ibr in combination with Nab-P/GCB. Methods: The randomized, multicenter, double-blind, phase 2/3 RESOLVE trial (NCT02436668; PCYC-1137-CA) compares ibr vs. placebo, in combination with Nab-P/GCB, in approximately 320 patients with previously untreated metastatic pancreati...