Ibrutinib: Phase Ib data

Data from 10 evaluable patients with previously untreated CD20-positive B cell NHL in Part 1 of an open-label, U.S. and French Phase Ib trial showed that once-daily oral ibrutinib plus R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) led to an ORR of 100%, including 7 complete responses and 3 partial responses. DLTs included transient syncope and periorbital cellulitis at the 280 mg dose and gastritis at the 560 mg dose. The most common adverse events were neutropenia, thrombocytopenia, vomiting, anemia, nausea, fatigue, headache, constipation, diarrhea and dizziness. The trial enrolled 17 patients to receive once-daily 280, 420 or 560 mg oral ibrutinib plus standard doses of R-CHOP chemotherapy. An expansion cohort is evaluating the recommended Phase II dose of 560 mg ibrutinib plus R-CHOP chemotherapy in patients with newly diagnosed diffuse large B cell lymphoma (DLBCL). Data were presented at the American Society of Clinical Oncology meeting in Chicago.

Under a 2011 deal, Pharmacyclics is co-developing and co-commercializing its ibrutinib with J&J's Janssen Biotech Inc. unit (see BioCentury, Dec. 12, 2011). Ibrutinib has breakthrough therapy designation to treat chronic lymphocytic leukemia (CLL) or small cell lymphocytic lymphoma (SLL) in patients with chromosome 17p deletion and for relapsed or refractory mantle cell lymphoma (MCL) and Waldenstrom's macroglobulinemia. Ibrutinib is in the Phase II RESONATE-17 trial to treat CLL and SLL patients with chromosome 17p deletion and the Phase III RESONATE trial in CLL and SLL patients without the mutation. The compound is also in Phase III testing to treat MCL, for which Pharmacyclics expects to submit an NDA to FDA by year end. ...