TRANSLATE

Tuesday, 15 December 2015

IMBRUVICA® (ibrutinib) Phase 3 RAY Data Show Significant Improvements in Progression-Free Survival Versus Temsirolimus in Patients with Relapsed or Refractory Mantle Cell Lymphoma

ORLANDO, Fla. and HORSHAM, Pa., Dec. 7, 2015 /PRNewswire/ -- Data from the Phase 3 RAY (MCL3001) study, an investigational clinical trial, showed oral IMBRUVICA® (ibrutinib) significantly improved progression-free survival (PFS; the primary endpoint) versus intravenous temsirolimus in patients with relapsed or refractory mantle cell lymphoma (MCL). Janssen Biotech, Inc. announced IMBRUVICA was associated with a 57 percent reduction in the risk of disease 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 2015 American Society of Hematology (ASH) meeting in Orlando, FL. IMBRUVICA is jointly developed and commercialized by Janssen and Pharmacyclics LLC, an AbbVie company.

These results were presented in full by RAY study investigator Simon Rule, M.D., Consultant Haematologist, Department of Haematology, and Head of the Lymphoma Service, Derriford Hospital, Plymouth, UK, during the "Lymphoma: Therapy with Biologic Agents, excluding Pre-Clinical Models: Biologic Agents in B Cell Lymphoma" session on Monday, December 7 at 7:00 a.m. ET.
"Mantle cell lymphoma is an aggressive blood cancer associated with poor prognoses, as patients typically achieve only short-term remissions with conventional chemotherapy," said Dr. Rule. "The benefits seen with IMBRUVICA versus temsirolimus in the Phase 3 RAY trial show that IMBRUVICA provides a treatment option with a favorable efficacy and safety profile for patients living with this disease."
RAY is a Janssen-sponsored, Phase 3, randomized, open-label trial that enrolled 280 patients with relapsed or refractory MCL who were randomized to receive either IMBRUVICA (N=139) or temsirolimus (N=141). Patients were given either oral IMBRUVICA 560 mg per the approved label or intravenous temsirolimus (175 mg on days 1, 8 and 15 of cycle 1; 75 mg on days 1, 8 and 15 of all subsequent 21-day cycles) until disease progression or unacceptable toxicity. The primary endpoint of the study was PFS as assessed by the Independent Review Committee (IRC); secondary endpoints included overall response rate (ORR), overall survival (OS) and safety, among others.
IMBRUVICA significantly improved PFS as determined by the IRC compared with temsirolimus, reducing the risk of disease progression or death by 57 percent after a median follow-up of 20 months (HR 0.43; [95 percent CI, 0.32-0.58]; P<0.0001). The median PFS for patients who received IMBRUVICA was 14.6 months, compared with 6.2 months for those who received temsirolimus. Notably, at two years, patients receiving IMBRUVICA had a 41 percent PFS rate, compared with seven percent in those receiving temsirolimus.
IMBRUVICA demonstrated a significantly higher ORR versus temsirolimus (72 percent vs. 40 percent, respectively; difference 31.5 percent [95 percent CI, 20.5-42.5]; P<0.0001). Twenty-six patients who received IMBRUVICA (19 percent) achieved a complete response (CR), while only two patients who received temsirolimus experienced a CR (1 percent). These findings are consistent with results from previous trials. Treatment with IMBRUVICA significantly lengthened the time to a patient's next treatment. The median time to next treatment was not reached with IMBRUVICA, versus 11.6 months median time to next treatment with temsirolimus (P<0.0001). These data articulate that subsequent treatments were required more frequently following temsirolimus treatment compared to treatment with IMBRUVICA.
In addition, the median treatment duration was four times longer in patients taking IMBRUVICA (14.4 months vs. 3.0 months, respectively). Median OS was not reached with IMBRUVICA, as compared to 21.3 months with temsirolimus.
"We are encouraged by the positive results achieved in the Phase 3 RAY trial, which confirm the clinical benefit seen in the earlier Phase 2 study that was the basis for the initial U.S. Accelerated Approval in relapsed MCL in 2013," said Craig Tendler, M.D., Vice President, Late-Stage Development and Global Medical Affairs for Oncology, Janssen Research & Development. "As we continue to study IMBRUVICA for the treatment of serious blood cancers, we are very encouraged to see the superior benefit/risk profile of this therapy when evaluated against existing treatments in this setting."
Overall, six percent of IMBRUVICA patients and 26 percent of temsirolimus patients discontinued treatment due to adverse events (AEs); the most common treatment-emergent AEs (≥20 percent) of any Grade for IMBRUVICA, were diarrhea (29 percent), cough (22 percent) and fatigue (22 percent); the most common treatment-emergent AEs (>20 percent) of any Grade for temsirolimus, were thrombocytopenia (56 percent), anemia (43 percent), diarrhea (31 percent), fatigue (29 percent), neutropenia (26 percent), epistaxis (24 percent), cough (22 percent), peripheral edema (22 percent), nausea (22 percent), pyrexia (21 percent) and stomatitis (21 percent). The most common hematological AEs (≥10 percent) were thrombocytopenia (18 percent vs. 56 percent), anemia (18 percent vs. 43 percent) and neutropenia (16 percent vs. 26 percent). After a median follow up of 20 months, 42 percent of patients in the IMBRUVICA group had died and 45 percent of patients in the temsirolimus group had died. The most common cause of death associated with IMBRUVICA was disease progression, while deaths in the temsirolimus arm were primarily attributed to AEs. Grade 3 or higher AEs include atrial fibrillation which was reported in five patients (4 percent) treated with IMBRUVICA and in two patients (1 percent) treated with temsirolimus, and major bleeding which was reported in 14 patients (10 percent) treated with IMBRUVICA and in nine patients (6 percent) treated with temsirolimus.



No comments:

Post a Comment