Second Phase 3 Study of YERVOY(TM) (ipilimumab) in Metastatic Melanoma Meets Primary Endpoint of Overall Survival

Princeton, New Jersey (ots/PRNewswire) -

- Study 024 Evaluated Newly-Diagnosed Patients Treated with
YERVOY at Investigational Dose of 10mg/kg in Combination with
Dacarbazine vs. Dacarbazine Alone

- Forty-Seven Percent of Patients Treated with YERVOY Plus
Dacarbazine Alive at One Year, 28 Percent Alive at Two Years and 20
Percent Alive at Three Years

- In Patients with an Objective Response, Median Duration was
19.3 Months in YERVOY Plus Dacarbazine Arm vs. 8.1 Months for
Dacarbazine Alone Arm

- Types of Safety Events Consistent with Prior Experience; Higher
Incidence of Liver Enzyme Elevations and No Drug-Related Deaths in
YERVOY Arm Reported

- Results Published in New England Journal of Medicine and
Presented at 47th Annual Meeting of the American Society of Clinical
Oncology

Bristol-Myers Squibb Company today announced results from a
second Phase 3 randomized, double blind study demonstrating that
YERVOY(TM) (ipilimumab) prolonged the lives of patients with
metastatic melanoma. The data were published today in the New England
Journal of Medicine and presented at the 47th Annual Meeting of the
American Society of Clinical Oncology. (Abstract #5)

In study 024, patients had not received prior treatment for
metastatic melanoma and were randomized to receive the
investigational dose of YERVOY 10mg/kg in combination with the
chemotherapy dacarbazine (850 mg/m2) or dacarbazine alone. There was
a significant improvement in overall survival (HR = 0.72, P=0.0009)
for patients treated with YERVOY plus dacarbazine vs. those who
received dacarbazine alone. Higher estimated survival rates were
observed at one year (47.3% vs. 36.3%), two years (28.5% vs. 17.9 %)
and three years (20.8% vs. 12.2 %; three years was analyzed post hoc)
in patients treated with YERVOY plus dacarbazine vs. those who
received dacarbazine alone.

Overall, the types of adverse events (AEs) attributed to YERVOY
in study 024 were generally mechanism (immune)- based and consistent
with prior YERVOY studies. A higher-than-expected rate of liver
enzyme elevations was reported. There were no gastrointestinal
perforations in either arm of the study and no drug-related deaths in
the YERVOY arm. Adverse events associated with YERVOY were managed
with protocol-specific guidelines, including the administration of
systemic corticosteroids, dose interruption/discontinuation and/or
other immunosuppressants.

"We now have Phase 3 data demonstrating that ipilimumab improved
survival in patients with metastatic melanoma in both the first and
second-line settings," said Jedd Wolchok, M.D., Ph.D., Memorial
Sloan-Kettering Cancer Center, and presenter of the study results.
"For physicians who treat cancer, improving overall survival is what
we strive for with our patients and I believe ipilimumab is a
foundational therapy for metastatic melanoma."

"In this study, the one, two and three-year estimated survival
rates demonstrate prolonged survival for patients in the YERVOY plus
dacarbazine arm," said Caroline Robert, M.D., Institute Gustave
Roussy in Paris, France, and lead author on the New England Journal
of Medicine paper. "Results from this study are significant in a
disease as devastating as metastatic melanoma."

The combination of dacarbazine with YERVOY is not an FDA
approved-regimen. In addition, study 024 was not designed to compare
the safety and efficacy of the FDA- approved monotherapy dose of 3
mg/kg for unresectable or metastatic melanoma vs. the investigational
dose of 10 mg/kg. Bristol-Myers Squibb plans to conduct a
head-to-head Phase 3 study comparing the safety and efficacy of these
two doses given as a monotherapy in patients with unresectable or
metastatic melanoma.

Detailed Study Results

In study 024, there was a significant improvement in overall
survival (HR = 0.72, P=0.0009) in the YERVOY plus dacarbazine arm vs.
the dacarbazine alone arm. The estimated rates of overall survival in
the YERVOY plus dacarbazine arm vs. the dacarbazine alone arm were
47.3% vs. 36.3% at one year, 28.5% vs. 17.9 % at two years and 20.8%
vs. 12.2 % at three years (three years was analyzed post hoc). Median
overall survival in the YERVOY plus dacarbazine arm was 11.2 months
(95% CI: 9.4, 13.6) compared with 9.1 months (95% CI: 7.8, 10.5) in
the dacarbazine alone arm. The best objective response rate was 15.2%
(38/250) in the YERVOY plus dacarbazine arm and 10.3% (26/252) in the
dacarbazine alone arm. The median duration of response in those
patients who achieved an objective response (CR and/or PR) was 19.3
months (95% CI: 12.1, 26.1) in the YERVOY plus dacarbazine arm (n=38)
and 8.1 months (95% CI: 5.19, 19.8) in the dacarbazine alone arm
(n=26)

Grade 3/4 adverse events (AEs) were observed in 56% of the YERVOY
plus dacarbazine arm and 28% of the dacarbazine alone arm. Select AEs
(all grades), which were reported at higher incidence in the YERVOY
plus dacarbazine arm included: alanine transaminase elevation (33%
versus 6%), aspartate transaminase elevation (29% versus 6%),
diarrhea (36% versus 25%), pruritis (30% versus 9%), and rash (25%
versus 7%). No gastrointestinal perforations were reported in either
arm of the study. No drug-related deaths were reported in the YERVOY
plus dacarbazine arm. One fatal gastrointestinal hemorrhage was
reported in the dacarbazine arm.

The most frequent reason for discontinuation of study drug
therapy was disease progression (46.2% in the YERVOY plus dacarbazine
group and 77.3% in the dacarbazine group). Discontinuation due to
drug-related toxicity was reported in 36% of patients in the YERVOY
plus dacarbazine and 4% in the dacarbazine alone arm. A total of 37%
of patients in the YERVOY plus dacarbazine arm and 66% of patients in
the dacarbazine alone arm received all four doses of YERVOY or
placebo.

About the Study

Study 024 is a multi-national, randomized, double-blind Phase 3
study that evaluated the safety and efficacy of YERVOY (10 mg/kg)
plus dacarbzine (850 mg/m2) vs. dacarbazine alone in treatment naive
patients with Stage III unresectable or Stage IV metastatic melanoma.
Patients who received prior adjuvant therapy were allowed in the
trial. Patients were randomly assigned in a 1:1 ratio to receive
either YERVOY plus dacarbazine (n=250) or dacarbazine plus placebo
(n=252) at Weeks 1, 4, 7, 10 followed by dacarbazine alone every 3
weeks through Week 22 (induction phase). If drug intolerance or
progressive disease (PD) was noted during Weeks 12-24, treatment was
discontinued. At Week 24, patients who had stable disease (SD) or an
objective response (OR) during induction with no dose-limiting
toxicity could enter a maintenance phase in which they received
placebo or YERVOY every 12 weeks until PD, drug intolerance or end of
study.

The primary endpoint of study 024 was overall survival. Secondary
endpoints included progression-free survival, disease control rate,
best overall response rate by modified WHO criteria, time to
response, response duration, and safety.

About Metastatic Melanoma

Melanoma is a form of skin cancer characterized by the
uncontrolled growth of pigment-producing cells (melanocytes) located
in the skin. Metastatic melanoma is the deadliest form of the
disease, and occurs when cancer spreads beyond the surface of the
skin to other organs, such as the lymph nodes, lungs, brain or other
areas of the body. Some cancer cells can actively evade surveillance
by the immune system, allowing tumors to survive. Melanoma is mostly
curable when treated in its early stages. However, in its late
stages, the average survival rate is just 6 months with a 1-year
mortality rate of 75%, making it one of the most aggressive forms of
cancer. These rates are based on a meta-analysis of 42 Phase 2 trials
of more than 2,100 previously-treated and treatment-naïve patients
with Stage IV metastatic melanoma conducted by multiple cooperative
groups from 1975-2005. The incidence of melanoma has been increasing
for at least 30 years. The median age at diagnosis for melanoma is 57
and the median age at death is 67.

About YERVOY

In March 2011, the FDA approved YERVOY 3 mg/kg monotherapy for
patients with unresectable or metastatic melanoma. YERVOY was also
added to the National Comprehensive Cancer Network(R) (NCCN(R))
Clinical Practice Guidelines in Oncology (NCCN Guidelines(TM)) for
Melanoma as the only NCCN Category 1 FDA-approved agent for treatment
of metastatic melanoma. A category 1 designation is based on high
level evidence, such as randomized controlled trials, as well as
uniform NCCN consensus. Further details can be found at
http:/www.nccn.org.*

YERVOY, which is a recombinant, human monoclonal antibody, is the
first FDA-approved cancer immunotherapy that blocks the cytotoxic T-
lymphocyte antigen-4 (CTLA-4). CTLA-4 is a negative regulator of
T-cell activation. Ipilimumab binds to CTLA-4 and blocks the
interaction of CTLA-4 with its ligands, CD80/CD86. Blockade of CTLA-4
has been shown to augment T-cell activation and proliferation. The
mechanism of action of ipilimumab's effect in patients with melanoma
is indirect, possibly through T-cell mediated anti-tumor immune
responses.

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical company whose
mission is to discover, develop and deliver innovative medicines that
help patients prevail over serious diseases.

This press release contains "forward-looking statements" as that
term is defined in the Private Securities Litigation Reform Act of
1995 regarding product development. Such forward-looking statements
are based on current expectations and involve inherent risks and
uncertainties, including factors that could delay, divert or change
any of them, and could cause actual outcomes and results to differ
materially from current expectations. No forward-looking statement
can be guaranteed. Among other risks, there can be no guarantee that
the investigational compounds described in this release will receive
regulatory approvals or, if approved, that they will become
commercially successful. There is also no guarantee that the
investigational uses of currently-approved products described in this
release will lead to additional approved indications for such
products. Forward-looking statements in this press release should be
evaluated together with the many uncertainties that affect
Bristol-Myers Squibb's business, particularly those identified in the
cautionary factors discussion in Bristol-Myers Squibb's Annual Report
on Form 10-K for the year ended December 31, 2010, in our Quarterly
Reports on Form 10-Q and our Current Reports on Form 8-K.
Bristol-Myers Squibb undertakes no obligation to publicly update any
forward-looking statement, whether as a result of new information,
future events or otherwise.

ots Originaltext: Bristol-Myers Squibb GmbH & Co.KG aA
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Media: Ela Zawislak, +33-615-523-580, elzbieta.zawislak@bms.com