Results from Three Phase 2 Studies Reported a Two-Year Survival Rate Ranging from 30 to 42 Percent in Metastatic Melanoma Patients Treated with Ipilimumab (10 mg/kg)
PRINCETON, N.J.--(BUSINESS WIRE)--May. 31, 2009--Bristol-Myers
Squibb Company (NYSE: BMY) and Medarex,
Inc. (NASDAQ: MEDX) today announced updated survival results from
follow-up extensions of three Phase 2 ipilimumab studies of patients
with advanced metastatic melanoma (Stage III or IV). The two-year
survival rate ranged from 29.8 to 41.8 percent in patients who received
ipilimumab (10 mg/kg). Results of the survival data were presented at
the 45th Annual Meeting of the American Society of Clinical
Oncology in Orlando, FL., May 29 -- June 2, 2009.
The results are based on follow-up of up to 37.5 months (median
follow-up ranging from 10.1 to 16.3 months) of the patient population
from studies 008, 022 and 007 treated with 10 mg/kg of ipilimumab
(induction and maintenance) and, specifically, showed:
Two-year survival rate of 32.8 percent (95% CI: 25.37%- 40.49%) in
patients who had progressed while on or after receiving standard
treatment (Study 008, Abstract #9033);
Two-year survival rate of 29.8 percent (95% CI: 19.13%- 41.14%) in
patients who were previously treated, relapsed or failed to respond to
experimental treatment or were unable to tolerate currently approved
therapies (Study 022, Abstract #9033);
Two-year survival rate of 40.6 percent (95% CI: 27.12%- 54.37%) and
41.8 percent (95% CI: 28.30%- 55.46%) in patients receiving ipilimumab
plus budesonide or ipilimumab plus placebo, respectively, which
included treatment-naïve patients and patients previously treated with
therapy other than ipilimumab (Study 007, Abstract #9033).
Historical melanoma survival rates from previous clinical trials have
been estimated by a recent meta-analysis of 42 Phase 2 trials of over
2,100 patients with Stage III or IV metastatic melanoma indicating that,
at one year, approximately 25 percent of patients were alive. Results
from three separately published randomized Phase 3 studies using
dacarbazine as the control arm reported that, at two years,
approximately 8 to 12 percent of metastatic melanoma patients were alive.
The updated survival analyses did not include additional safety data. As
previously reported, safety results include follow-up of up to 16.3
months with a median follow-up ranging from 4.7 to 5.65 months. The most
common immune-related adverse events were rash, diarrhea and hepatitis.
Grade 3 and 4 immune-related adverse event rates were approximately 20
to 29 percent and zero to 12 percent, respectively, in patients who
received 10 mg/kg of ipilimumab. Adverse events were managed with the
use of supportive care and systemic steroids using established treatment
guidelines in the majority of patients. Additionally, the use of
systemic steroids to manage adverse events does not appear to diminish
or impact the clinical effect of ipilimumab (Abstract #9037).
"The ongoing survival data observed with ipilimumab are encouraging,
particularly because the advanced melanoma patient population currently
has limited treatment options," said Steven J. O'Day, M.D., Chief of
Research and Director of the Melanoma Program at The Angeles Clinic and
Research Institute, California. "The potential of ipilimumab is also
underscored by the fact that we can report two-year survival results
from these studies involving a significant number of metastatic melanoma
patients."
Candidate Biomarkers of Ipilimumab
Researchers also presented an exploratory analysis from four Phase 2
ipilimumab studies (008, 022, 007 and 004) that looked at the
association between clinical activity and multiple potential biomarkers,
including the change in absolute lymphocyte count (ALC) in melanoma
patients after they received ipilimumab (Abstracts #9008 and #3020). ALC
is a measure of the number of immune cells in circulation.
In a combined analysis of studies 007, 008 and 022, clinical activity
was associated with an increase in the rate of change in ALC. Patients
with clinical activity had a higher average increase in ALC over time
than did patients without clinical activity (P=0.0013) and no patient
with a decrease in ALC over time had clinical activity. This association
was separately confirmed in Study 004. Increases in ALC following
administration of ipilimumab were also significantly associated with
dose (studies 007, 008, 022: P<0.0001; study 004: P=0.0015), favoring
the 10 mg/kg regimen. Based on these early biomarker findings, further
research to explore the implication of ALC and other potential
biomarkers of clinical activity of ipilimumab continues.
About Studies 008, 022 and 007
The three studies enrolled a total of 487
patients across North
America, Europe, South America, Africa and Australia with Stage III or
Stage IV metastatic melanoma treated with ipilimumab therapy (0.3 mg/kg,
3.0 mg/kg or 10 mg/kg every three weeks for up to four doses, followed
by maintenance dosing every 12 weeks). Specifically, the three Phase 2
monotherapy trials include:
A Phase 2 open-label, single-arm trial (008) evaluating overall
response rate in 155 patients who progressed while on or after
receiving standard treatment;
A Phase 2 randomized, double-blind trial (022) evaluating the efficacy
of three dose levels of ipilimumab in 217 patients who were previously
treated, relapsed or failed to respond to experimental treatment or
were unable to tolerate currently approved therapies; and
A Phase 2 randomized, double-blind trial (007) evaluating the rate of
Grade 2+ diarrhea in 115 patients receiving ipilimumab with or without
prophylactic oral budesonide.
The primary endpoint of studies 008 and 022 was best overall response
rate and the primary endpoint of study 007 was to compare the rate of
Grade 2+ diarrhea in patients receiving ipilimumab with or without
prophylactic oral budesonide. Overall survival, one-year survival rates,
disease control rate, stable disease, and other measurements of
anti-tumor activity and patterns of responses were secondary endpoints
in studies 008, 022 and 007. The two-year survival data reported are
current (through March, 2009) for all subjects followed: 93.6% from
study 008, 91.7% from study 022 and 84.2% and 82.8% from the two
subgroups of study 007 (placebo and budesonide, respectively).
About Study 004
Study 004 is a Phase 2 randomized, double-blind biomarker trial. The
study enrolled 82 patients with advanced melanoma who were previously
treated with therapy other than ipilimumab or who received no prior
therapy. All patients received ipilimumab therapy (3.0 mg/kg or 10
mg/kg). Pre- and post-treatment (week four) tumor biopsies were
performed to assess associations between tumor biomarkers and clinical
activity of ipilimumab. Clinical activity was defined as complete or
partial response or stable disease at ≥24 weeks using modified World
Health Organization criteria.
