IMBRUVICA® (Ibrutinib) Phase 3 RAY Data Show Significant Reductions in Disease Progression versus Temsirolimus in Relapsed/Refractory Mantle Cell Lymphoma Patients

Today AbbVie

, a global biopharmaceutical company, announced results from the Phase 3 RAY (MCL3001) trial, which showed IMBRUVICA® (ibrutinib) significantly prolonged progression-free survival (PFS; the primary endpoint) and improved overall response rates (ORR; a key secondary endpoint) in patients with relapsed or refractory mantle cell lymphoma (MCL), compared with temsirolimus. Notably, IMBRUVICA was associated with a 57% reduction in the risk of progression or death with a median follow-up of 20 months. These data were published online in The Lancet today and presented in an oral session at the 57th Annual American Society of Hematology (ASH) Meeting and Exposition in Orlando, FL. IMBRUVICA is jointly developed and commercialized by Pharmacyclics LLC, an AbbVie Company, and Janssen Biotech, Inc. Mantle cell lymphoma is an aggressive form of blood cancer which arises from B cells, a type of white blood cell (lymphocyte) that originates in the bone marrow.1,2 MCL is more prevalent in men than women.1 The majority of patients are in their mid-60s at diagnosis and the median overall survival rate is three to four years.1,3 "MCL patients typically achieve only short-term remissions with conventional therapies, so the positive results seen with IMBRUVICA in this Phase 3 trial are particularly striking," said Simon Rule, M.D., Consultant Haematologist, Department of Haematology, and Head of the Lymphoma Service, Derriford Hospital, Plymouth, UK, and RAY study investigator. "As clinicians, we strive to ensure our patients receive safe and effective treatment options. The RAY data show IMBRUVICA was associated with an improved risk-benefit profile compared to temsirolimus." IMBRUVICA significantly improved PFS as determined by an Independent Review Committee (IRC) compared to treatment with temsirolimus, resulting in a reduction in the risk of disease progression or death by 57% after a median follow-up of 20 months (HR 0.43 [95% CI, 0.32-0.58; P<0.0001]). The median PFS for IMBRUVICA-treated patients was 14.6 months compared to 6.2 months for patients treated with temsirolimus. IMBRUVICA was associated with a significantly higher ORR versus temsirolimus as assessed by an IRC (72% vs. 40%, respectively; difference 31.­5% [95% CI, 20­.5–42.­5]; p<0­0001). Twenty-six patients who received IMBRUVICA (19%) achieved a complete response (CR), while only two patients who received temsirolimus experienced a CR (1%). Of note, the median treatment duration was four times longer in patients taking IMBRUVICA than those receiving temsirolimus (14.4 months vs. 3.0 months, respectively). Median overall survival was not reached with IMBRUVICA, as compared to 21.3 months with temsirolimus (HR, 0.76; [95% CI, 0.53-1.09). These findings are consistent with results from previous single-arm Phase 2 studies evaluating the safety and efficacy of IMBRUVICA in patients with MCL. "These data confirm results from an earlier Phase 2 study, which formed the basis of an accelerated approval of IMBRUVICA for MCL patients who have received at least one prior therapy in the U.S.," said Darrin Beaupre, M.D., Ph.D., Head of Early Development and Immunotherapy at Pharmacyclics. "We are pleased to see these results confirm the benefit of IMBRUVICA for patients with this aggressive form of blood cancer." The most common treatment-emergent adverse events (AEs >20%) observed in IMBRUVICA, included diarrhea (29%), cough (22%) and fatigue (22%); AEs observed in temsirolimus, included thrombocytopenia (56%), anemia (43%), diarrhea (31%), fatigue (29%), neutropenia (26%), epistaxis (24%), cough (22%), peripheral edema (22%) nausea (22%), pyrexia (21%) and stomatitis (21%). The most common hematological AEs (>10%) were thrombocytopenia (18% vs. 56%), anemia (18% vs. 43%) and neutropenia (16% vs. 26%). Overall, 7% of IMBRUVICA patients and 26% of temsirolimus patients discontinued treatment due to AEs. After a median follow-up of 20 months, 42% of IMBRUVICA patients died and 45% of patients who received temsirolimus died.