Date: 2016-02-11
Type of information: Halting of the trial
phase: 3
Announcement: halting of the trial
Company: Incyte (USA - DE)
Product: ruxolitinib and capecitabine
Action
mechanism: kinase inhibitor/tyrosine kinase inhibitor. Jakafi®/Jakavi® (INC424, ruxolitinib) is an oral inhibitor of the JAK 1 and JAK 2 tyrosine kinases that are involved in regulating blood and immunological functioning. Myelofibrosis is associated with the deregulation of JAK 1 and 2. The product was approved by the European Commission in August 2012 for the treatment of disease-related splenomegaly or symptoms in adult patients with primary myelofibrosis (also known as chronic idiopathic myelofibrosis), post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis.
Novartis licensed INC424 (ruxolitinib) from Incyte Corporation for development and commercialization outside the United States. Both the European Commission and the FDA granted INC424 (ruxolitinib) orphan drug status for myelofibrosis. Jakavi® is marketed in the United States by Incyte Corporation under the name Jakafi® for the treatment of patients with intermediate or high-risk myelofibrosis.
Disease: metastatic pancreatic cancer
Therapeutic area: Cancer - Oncology
Country:
Trial
details: JANUS 1 (INCB 18424-362) 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 primary objective of the study 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.
Latest
news: * On February 11, 2016, Incyte announced its decision to discontinue the Phase 3 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 of JANUS 1 demonstrated that ruxolitinib plus capecitabine did not show a sufficient level of efficacy to warrant continuation. Incyte's dose finding study of INCB39110 (a selective JAK1 inhibitor) as first-line treatment for metastatic pancreatic cancer, will also be discontinued. Incyte will work with investigators to appropriately conclude these studies in a manner consistent with the best interest of each patient. Data from these studies will be analyzed and shared with the scientific community over the coming months.
Following these results, and the previously announced interim analysis of the Phase 2 sub-study of ruxolitinib or placebo in combination with regorafinib in patients with metastatic colorectal cancer and high C-reactive protein (CRP), ongoing Incyte -sponsored trials of ruxolitinib in solid tumors will be discontinued, including the Phase 3 JANUS 2 study in pancreatic cancer, the Phase 2 sub-study in patients with metastatic colorectal cancer and low CRP and the Phase 2 studies in breast and lung cancer.
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 (anti-PD-1 antibody), epacadostat (Incyte's IDO1 inhibitor), or INCB50465 (Incyte's PI3Kd inhibitor) to assess the therapeutic utility of JAK1 inhibition based on its effects on the tumor microenvironment. Additionally, the potential impact of JAK1 inhibition on improving the benefit of targeted therapies will be investigated via a Phase 1/2 study of INCB39110 plus osimertinib, AstraZeneca's next generation EGFR inhibitor.
