A Phase III study comparing ibrutinib versus temsirolimus has been recently initiated by Janssen. This is a randomized, multi-center Phase III trial of ibrutinib as a monotherapy in relapsed/refractory MCL patients who received at least one prior rituximab-containing chemotherapy regimen. The primary endpoint of the study is progression-free survival when compared to temsirolimus. This study is planned to enroll 280 patients outside the US.
Other Clinical Development Highlights
At the 2012 ASH Annual Meeting, Pharmacyclics and its investigators gave a multitude of presentations showing research and clinical results of using ibrutinib in a variety of diseases. The following summarizes two oral presentations and one poster showing recent trial results in diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and multiple myeloma (MM).
ASH Annual Meeting Oral Presentation
The Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib, has Preferential Activity in the ABC Subtype of Relapsed/Refractory de Novo Diffuse Large B-cell Lymphoma (DLBCL): Interim Results of a Multicenter, Open-label, Phase 2 Study Wyndham H. Wilson, M.D., Ph.D., National Cancer Institute
Preliminary results were reported from the multicenter, open-label, Phase II study of ibrutinib in 70 subjects with relapsed or refractory DLBCL in two genetically distinct subtypes of DLBCL, the activated B-cell (ABC) subtype and the germinal center (GC) subtype. The ABC subtype appears to be more driven by B cell receptor signaling. The ORR in the heavily pre-treated population was 23% (16 of 70 patients). Responses were primarily in the ABC subtype with 12 of 29 patients (41%) responding (5 complete responses and 7 partial responses). In the 20 GC patients only 1 patient (5%) had a partial response. This study supports the use of ABC DLBCL molecular subtype as a biomarker for enrichment of patients for future ibrutinib studies. The safety profile is favorable, with Grade 3 or higher Adverse Events, related and unrelated, in typically 5% - 10% of the patients.
Pharmacyclics and its partner Janssen recently announced a Phase I dose escalating study of ibrutinib in combination with R-CHOP in newly diagnosed DLBCL patients. The primary objective is to define a safe and tolerable dose for this combination. This area of ibrutinib development continues to evolve and further updates are planned for the second half of 2013.