Incyte Corporation has announced its decision to discontinue a phase II study (JANUS 1) of ruxolitinib or placebo in combination with capecitabine for the second-line treatment of patients with advanced or metastatic pancreatic cancer. The decision to stop the study was made after a planned interim analysis demonstrated that ruxolitinib plus capecitabine did not show a sufficient level of efficacy to warrant continuation.
Following these results, and the previously announced interim analysis of the phase II substudy of ruxolitinib or placebo in combination with regorafinib in patients with metastatic colorectal cancer and high C-reactive protein (CRP) levels, ongoing trials of ruxolitinib in solid tumors will be discontinued, including the phase III JANUS 2 trial in pancreatic cancer, a phase II substudy in patients with metastatic colorectal cancer and low CRP levels, and phase II studies in breast and lung cancer. A dose-finding study of INCB39110 (a selective Janus kinase 1 [JAK1] inhibitor) as first-line treatment for metastatic pancreatic cancer will also be discontinued.
Ongoing studies of ruxolitinib and selective JAK1 inhibitors in hematology indications will continue. Ongoing studies of selective JAK1 inhibition in solid tumor indications that are based on different hypotheses will also continue. These include a series of studies evaluating INCB39110 in combination with either pembrolizumab (an anti-programmed death-1 [PD-1] antibody), epacadostat (an indoleamine 2,3-dioxygenase 1 [IDO1] inhibitor), or INCB50465 (a phosphoinositide 3-kinase [PI3K]-delta inhibitor) to assess the therapeutic utility of JAK1 inhibition based on its effects on the tumor microenvironment. In addition, the potential effect of JAK1 inhibition on improving the benefit of targeted therapies will be investigated in a phase I/II study of INCB39110 plus osimertinib, AstraZeneca’s next-generation epidermal growth factor receptor (EGFR) inhibitor.
The JANUS 1 trial was a randomized, double-blind, Phase 3 study of ruxolitinib or placebo in combination with capecitabine in patients with advanced or metastatic pancreatic cancer who had failed or were intolerant of first-line chemotherapy. The study’s primary objective was to evaluate and compare the overall survival of patients treated with ruxolitinib in combination with capecitabine versus capecitabine alone. Secondary objectives evaluated and compared the efficacy of the two treatment groups with respect to progression-free survival, overall tumor response, and duration of response, as well as safety and tolerability.
Ruxolitinib is a first-in-class JAK1/JAK2 inhibitor approved by the FDA for the treatment of patients with polycythemia vera (PV) who have had an inadequate response to or are intolerant of hydroxyurea. Ruxolitinib is also indicated for the treatment of patients with intermediate- or high-risk myelofibrosis (MF), including primary MF, post-PV MF, and post–essential thrombocythemia MF.
Ruxolitinib is not approved anywhere in the world as treatment for metastatic pancreatic cancer.
Source: Incyte Corporation; February 11, 2016.