Pharmacyclics and its collaborators provided clinical and pre-clinical presentations on ibrutinib and ibrutinib combinations at the 2012 ASH Annual Meeting, including six oral presentations and three posters describing the recent clinical trials and further insights into the mechanism of action of ibrutinib in CLL/SLL patients. A multicenter, open-label, single agent Phase Ib/II study of ibrutinib in subjects with CLL/SLL either relapsed/refractory or treatment-naive. This study, which completed enrollment in July 2011 with 116 patients treated with ibrutinib monotherapy, was designed to assess safety, tolerability, and efficacy of ibrutinib at two dose levels. With a maximum follow up of 26 months, it was estimated that 96% of the treatment-naive and 75% of the relapsed-refractory/high-risk patients are without progression. Responses were independent of high risk clinical genetic features. Continuous dosing was well tolerated with a reported lack of detrimental impact on immunoglobulins or hematologic parameters. Most adverse events were Grade 2 or less in severity, with the most common being diarrhea, fatigue, upper respiratory tract infection, rash, nausea and arthralgias. Another presentation was based on findings from a Phase 2, single-center trial with 40 high risk CLL patients treated with 420 mg/day ibrutinib in combination with rituximab, an anti-CD20 monoclonal antibody. The high risk patients had one of the following characteristics, all predictive of poor outcome to standard chemotherapy: deletion in chromosome 17p, mutation in the tumor suppressor gene TP53, deletion in chromosome 11q or relapse less than 36 months after chemo-immunotherapy. The results after a median follow-up of 4.8 months were profound in these high-risk patients, with an overall response rate of 83%. Treatment was well tolerated, with grade 3/4 adverse events reported in 13 cases that were largely unrelated to ibrutinib or the combination and transient, the company said.
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