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.
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