Yervoy (ipilimumab) Improves Overall Survival in Fully Resected Stage III Melanoma
Patients From Phase 3 Study
Yervoy demonstrated a 28% reduction in the risk of death versus placebo in first disclosure of overall
survival data from pivotal study CA184-029 (EORTC 18071)
Risk of distant metastasis was reduced by 24% with Yervoy compared to
placebo
With longer follow-up, the recurrence-free survival benefit and safety profile remained
consistent with the previously reported primary analysis
Bristol-Myers Squibb Company (NYSE: BMY) announced today superior efficacy with Yervoy 10 mg/kg versus
placebo on all survival endpoints in the Phase 3 trial CA184-029 (EORTC 18071) evaluating stage III melanoma patients who are at
high risk of recurrence following complete surgical resection. In the study, Yervoy compared with placebo significantly
improved overall survival (OS) (HR=0.72 [95.1% CI: 0.58-0.88; p=0.001]), a secondary endpoint, with five-year OS rates at
65.4% in the Yervoy group and 54.4% in the placebo group. Distant metastasis-free survival (DMFS), a secondary endpoint, was
also significantly improved versus placebo (HR=0.76 [95.8% CI: 0.64-0.92; p=0.002]) and had five-year DMFS rates of 48.3%
and 38.9% in the Yervoy and placebo groups, respectively. In this updated five-year analysis, the recurrence-free survival
(primary endpoint) benefit observed previously with Yervoy was maintained (HR=0.76 [95% CI: 0.64-0.89; p<0.001).
The safety profile remained consistent with the initial analysis, with no new deaths or safety signals. The most common grade 3/4
immune-related adverse events in the Yervoy group were gastrointestinal (16.1%), hepatic (10.8%), and endocrine (7.9%).
These data were featured today, October 8, during the 2016 European Society for Medical Oncology Congress Press Program and
simultaneously published in The New England Journal of Medicine. The data will also be presented today during a Presidential
Symposium from 5:00-5:15 p.m. CEST (Abstract #LBA2_PR).
“Despite surgical intervention, most patients with stage III melanoma experience disease recurrence and progress to metastatic
disease, reinforcing the unmet need for effective systemic therapies in the adjuvant setting,” said Alexander M.M. Eggermont, M.D.,
Ph.D., director general, Cancer Institute Gustave Roussy in Villejuif, France. “The impact of Yervoy on overall survival,
distant-metastasis free survival, and recurrence-free survival observed in study -029 offers physicians new insights in the
treatment of adjuvant melanoma.”
In stage III melanoma, the disease has not yet spread to distant lymph nodes or to other parts of the body and requires surgical
resection of the primary tumor as well as the involved lymph nodes. The stage III patient population is heterogeneous with
disease-specific survival rates of 78%, 59%, and 40% for stage IIIA, IIIB, and IIIC melanoma, respectively.
“The results from study -029 are important data for the scientific community and underscore our ongoing dedication to improving
survival across stages of melanoma,” said Vicki Goodman, M.D., development lead, Melanoma and Genitourinary Cancers, Bristol-Myers
Squibb. “Yervoy is the first immune checkpoint inhibitor to demonstrate a statistically significant survival benefit for
high-risk patients with fully resected stage III melanoma. With further evaluation of our Immuno-Oncology agents and different
dosing options, we remain committed to further research across the full continuum of melanoma treatment.”
About CA184-029 (EORTC 18071)
CA184-029 (EORTC 18071), a study initiated in 2008 by the European Organization for Research and Treatment of Cancer (EORTC), is
a Phase 3, double-blind, placebo-controlled randomized trial evaluating the efficacy and safety of Yervoy 10 mg/kg in the
adjuvant setting for high-risk stage III melanoma. The independently-run trial involved 99 centers across 19 countries from the
EORTC’s pan-European network and specialized infrastructure. The trial enrolled eligible patients, which included those ≥18 years
of age who underwent complete resection of stage III cutaneous melanoma (excluding lymph node metastasis ≤1 mm or in-transit
metastasis). In the trial, patients were randomized to receive Yervoy 10 mg/kg (n=475) or placebo (n=476) as an
intravenous infusion every 3 weeks for 4 doses, followed by Yervoy 10 mg/kg or placebo every 12 weeks from Week 24
to Week 156 (three years), or until documented disease recurrence or unacceptable toxicity. Yervoy was studied
across a broad range of patient characteristics, including patients with stage IIIa with lymph node >1 mm (20%), IIIb (44%) or
IIIc with no in-transit metastases (36%); 42% had ulcerated primary lesions, and 58% had macroscopic lymph node involvement.
The primary endpoint was recurrence-free survival (RFS), defined as the time between the date of randomization and the date of
first recurrence or death, as assessed by the Independent Review Committee. This analysis was the basis of the Yervoy
approval in the United States for adjuvant treatment of melanoma at a dose of 10 mg/kg in October 2015. Secondary endpoints include
overall survival (OS), distant metastases-free survival (DMFS), safety and health-related quality of life.
In the study, Yervoy significantly improved RFS, the primary endpoint, versus placebo across all patient groups.
Updated five-year results demonstrated RFS remained significantly longer for Yervoy versus placebo, with a median RFS of
27.6 months (95% CI: 19.3-37.2) versus 17.1 months (95% CI: 13.6-21.6), respectively (HR=0.76; 95% CI: 0.64-0.89;
p<0.001).
Yervoy also demonstrated a significant improvement in OS, a secondary endpoint of the study, with a 28% reduction in the
risk of death versus placebo (HR=0.72 [95% CI: 0.58-0.88; p=0.001]) and an estimated five-year OS rate of 65.4% (95% CI:
60.8-69.6) for Yervoy versus 54.4% (95% CI: 49.7-58.9) for placebo. In addition, Yervoy showed a 24% reduction in the
risk of developing distant metastases versus placebo (HR=0.76 [95.8% CI: 0.64-0.92; p=0.002]), with an estimated five-year
DMFS rate of 48.3% with Yervoy versus 38.9% with placebo. The median DMFS was 48.3 months with Yervoy versus 27.5
months with placebo.
The safety profile of Yervoy based on this updated analysis was consistent with previously reported findings from
CA184-029 (EORTC 18071). In those initial findings, five patient deaths occurred due to drug-related adverse events (AE); no new
deaths have since been reported. Among the 471 patients who received Yervoy, 465 (98.7%) experienced an AE of any grade, and
255 patients (54.1%) experienced a grade 3 or 4 AE, whereas among 474 placebo-treated patients, 432 (91.1%) experienced an AE of
any grade, and 124 patients (26.2%) experienced a grade 3 or 4 AE. Immune-related AEs were more frequent with Yervoy than
with placebo. The most common grade 3/4 immune-related AEs in the Yervoy group were gastrointestinal (16.1%), hepatic
(10.8%), and endocrine (7.9%). The median time to onset of on-study grade 2-5 immune-related AEs ranged from 4.0 weeks (skin
immune-related adverse events) to 13.1 weeks (neurological immune-related adverse events). Endocrine grade 2-4 immune-related AEs
resolved in 51.5% of patients, and median time to resolution was 54.3 weeks. The majority (82-97%) of all other grade 2-4
immune-related AEs resolved, and median time to resolution ranged from 4.0 to 8.0 weeks.
About Advanced 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
the other organs, such as the lymph nodes, lungs, brain or other areas of the body. Melanoma is separated into five staging
categories (Stages 0-IV) based on the in-situ feature, thickness, and ulceration of the tumor, whether the cancer has spread to the
lymph nodes, and how far the cancer has spread beyond lymph nodes. Stage III melanoma has reached the regional lymph nodes but has
not yet spread to distant lymph nodes or to other parts of the body (metastasized) and requires surgical resection of the primary
tumor as well as the local lymph nodes.
Bristol-Myers Squibb: At the Forefront of Immuno-Oncology Science & Innovation
At Bristol-Myers Squibb, patients are at the center of everything we do. Our vision for the future of cancer care is focused on
researching and developing transformational Immuno-Oncology (I-O) medicines that will raise survival expectations in hard-to-treat
cancers and will change the way patients live with cancer.
We are leading the scientific understanding of I-O through our extensive portfolio of investigational and approved agents,
including the first combination of two I-O agents in metastatic melanoma, and our differentiated clinical development program,
which is studying broad patient populations across more than 20 types of cancers with 11 clinical-stage molecules designed to
target different immune system pathways. Our deep expertise and innovative clinical trial designs uniquely position us to advance
the science of combinations across multiple tumors and potentially deliver the next wave of I-O combination regimens with a sense
of urgency. We also continue to pioneer research that will help facilitate a deeper understanding of the role of immune biomarkers
and inform which patients will benefit most from I-O therapies.
We understand making the promise of I-O a reality for the many patients who may benefit from these therapies requires not only
innovation on our part but also close collaboration with leading experts in the field. Our partnerships with academia, government,
advocacy and biotech companies support our collective goal of providing new treatment options to advance the standards of clinical
practice.
About Yervoy
Yervoy is a recombinant, human monoclonal antibody that binds to the cytotoxic T-lymphocyte-associated antigen-4
(CTLA-4). CTLA-4 is a negative regulator of T-cell activity. Yervoy 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, including the
activation and proliferation of tumor infiltrating T-effector cells. Inhibition of CTLA-4 signaling can also reduce T-regulatory
cell function, which may contribute to a general increase in T-cell responsiveness, including the anti-tumor immune response. On
March 25, 2011, the U.S. Food and Drug Administration (FDA) approved Yervoy 3 mg/kg monotherapy for patients with
unresectable or metastatic melanoma. Yervoy is approved for unresectable or metastatic melanoma in more than 50
countries. There is a broad, ongoing development program in place for Yervoy spanning multiple tumor types.
U.S. Indications and Important Safety Information for YERVOY® (ipilimumab)
Indications
YERVOY® (ipilimumab) is indicated for the treatment of unresectable or metastatic melanoma.
YERVOY® (ipilimumab) is indicated for the adjuvant treatment of patients with cutaneous melanoma with pathologic
involvement of regional lymph nodes of more than 1 mm who have undergone complete resection, including total lymphadenectomy.
Important Safety Information
WARNING: IMMUNE-MEDIATED ADVERSE REACTIONS
YERVOY (ipilimumab) can result in severe and fatal immune-mediated adverse reactions. These immune-mediated reactions may
involve any organ system; however, the most common severe immune-mediated adverse reactions are enterocolitis, hepatitis,
dermatitis (including toxic epidermal necrolysis), neuropathy, and endocrinopathy. The majority of these immune-mediated reactions
initially manifested during treatment; however, a minority occurred weeks to months after discontinuation of YERVOY.
Permanently discontinue YERVOY and initiate systemic high-dose corticosteroid therapy for severe immune-mediated
reactions.
Assess patients for signs and symptoms of enterocolitis, dermatitis, neuropathy, and endocrinopathy and evaluate clinical
chemistries including liver function tests (LFTs), adrenocorticotropic hormone (ACTH) level, and thyroid function tests, at
baseline and before each dose.
Recommended Dose Modifications
Endocrine: Withhold YERVOY for systemic endocrinopathy. Resume YERVOY in patients with complete or partial resolution of adverse
reactions (Grade 0-1) and who are receiving <7.5 mg prednisone or equivalent per day. Permanently discontinue YERVOY for
symptomatic reactions lasting 6 weeks or longer or an inability to reduce corticosteroid dose to 7.5 mg prednisone or equivalent
per day.
Ophthalmologic: Permanently discontinue YERVOY for Grade 2-4 reactions not improving to Grade 1 within 2 weeks while receiving
topical therapy or requiring systemic treatment. All Other Organ Systems: Withhold YERVOY for Grade 2 adverse reactions. Resume
YERVOY in patients with complete or partial resolution of adverse reactions (Grade 0-1) and who are receiving <7.5 mg prednisone
or equivalent per day. Permanently discontinue YERVOY for Grade 2 reactions lasting 6 weeks or longer, an inability to reduce
corticosteroid dose to 7.5 mg prednisone or equivalent per day, and Grade 3 or 4 adverse reactions.
Immune-mediated Enterocolitis:
Immune-mediated enterocolitis, including fatal cases, can occur with YERVOY. Monitor patients for signs and symptoms of
enterocolitis (such as diarrhea, abdominal pain, mucus or blood in stool, with or without fever) and of bowel perforation (such as
peritoneal signs and ileus). In symptomatic patients, rule out infectious etiologies and consider endoscopic evaluation for
persistent or severe symptoms. Withhold YERVOY for moderate enterocolitis; administer anti-diarrheal treatment and, if persistent
for >1 week, initiate systemic corticosteroids (0.5 mg/kg/day prednisone or equivalent). Permanently discontinue YERVOY in
patients with severe enterocolitis and initiate systemic corticosteroids (1-2 mg/kg/day of prednisone or equivalent). Upon
improvement to ≤Grade 1, initiate corticosteroid taper and continue over at least 1 month. In clinical trials, rapid corticosteroid
tapering resulted in recurrence or worsening symptoms of enterocolitis in some patients. Consider adding anti-TNF or other
immunosuppressant agents for management of immune-mediated enterocolitis unresponsive to systemic corticosteroids within 3-5 days
or recurring after symptom improvement. In patients receiving YERVOY 3 mg/kg in Trial 1, severe, life-threatening, or fatal
(diarrhea of ≥7 stools above baseline, fever, ileus, peritoneal signs; Grade 3-5) immune-mediated enterocolitis occurred in 34
YERVOY-treated patients (7%) and moderate (diarrhea with up to 6 stools above baseline, abdominal pain, mucus or blood in
stool; Grade 2) enterocolitis occurred in 28 YERVOY-treated patients (5%). Across all YERVOY-treated patients (n=511), 5
(1%) developed intestinal perforation, 4 (0.8%) died as a result of complications, and 26 (5%) were hospitalized for severe
enterocolitis. Infliximab was administered to 5 (8%) of the 62 patients with moderate, severe, or life-threatening immune-mediated
enterocolitis following inadequate response to corticosteroids. In patients receiving YERVOY 10 mg/kg in Trial 2, Grade 3-5
immune-mediated enterocolitis occurred in 76 patients (16%) and Grade 2 enterocolitis occurred in 68 patients (14%). Seven (1.5%)
developed intestinal perforation and 3 patients (0.6%) died as a result of complications.
Immune-mediated Hepatitis:
Immune-mediated hepatitis, including fatal cases, can occur with YERVOY. Monitor LFTs (hepatic transaminase and bilirubin
levels) and assess patients for signs and symptoms of hepatotoxicity before each dose of YERVOY. In patients with hepatotoxicity,
rule out infectious or malignant causes and increase frequency of LFT monitoring until resolution. Withhold YERVOY in patients with
Grade 2 hepatotoxicity. Permanently discontinue YERVOY in patients with Grade 3-4 hepatotoxicity and administer systemic
corticosteroids (1-2 mg/kg/day of prednisone or equivalent). When LFTs show sustained improvement or return to baseline,
initiate corticosteroid tapering and continue over 1 month. Across the clinical development program for YERVOY, mycophenolate
treatment has been administered in patients with persistent severe hepatitis despite high-dose corticosteroids. In patients
receiving YERVOY 3 mg/kg in Trial 1, severe, life-threatening, or fatal hepatotoxicity (AST or ALT elevations >5× the ULN or
total bilirubin elevations >3× the ULN; Grade 3-5) occurred in 8 YERVOY-treated patients (2%), with fatal hepatic failure in
0.2% and hospitalization in 0.4%. An additional 13 patients (2.5%) experienced moderate hepatotoxicity manifested by LFT
abnormalities (AST or ALT elevations >2.5× but ≤5× the ULN or total bilirubin elevation >1.5× but ≤3× the ULN; Grade 2). In a
dose-finding trial, Grade 3 increases in transaminases with or without concomitant increases in total bilirubin occurred in 6 of 10
patients who received concurrent YERVOY (3 mg/kg) and vemurafenib (960 mg BID or 720 mg BID). In patients receiving YERVOY 10 mg/kg
in Trial 2, Grade 3-4 immune-mediated hepatitis occurred in 51 patients (11%) and moderate Grade 2 immune-mediated hepatitis
occurred in 22 patients (5%). Liver biopsy performed in 6 patients with Grade 3-4 hepatitis showed evidence of toxic or autoimmune
hepatitis.
Immune-mediated Dermatitis:
Immune-mediated dermatitis, including fatal cases, can occur with YERVOY. Monitor patients for signs and symptoms of dermatitis
such as rash and pruritus. Unless an alternate etiology has been identified, signs or symptoms of dermatitis should be considered
immune-mediated. Treat mild to moderate dermatitis (e.g., localized rash and pruritus) symptomatically; administer topical or
systemic corticosteroids if there is no improvement within 1 week. Withhold YERVOY in patients with moderate to severe signs and
symptoms. Permanently discontinue YERVOY in patients with severe, life-threatening, or fatal immune-mediated dermatitis (Grade
3-5). Administer systemic corticosteroids (1-2 mg/kg/day of prednisone or equivalent). When dermatitis is controlled,
corticosteroid tapering should occur over a period of at least 1 month. In patients receiving YERVOY 3 mg/kg in Trial 1, severe,
life-threatening, or fatal immune-mediated dermatitis (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis, or rash
complicated by full thickness dermal ulceration, or necrotic, bullous, or hemorrhagic manifestations; Grade 3-5) occurred in 13
YERVOY-treated patients (2.5%); 1 patient (0.2%) died as a result of toxic epidermal necrolysis and 1 additional patient required
hospitalization for severe dermatitis. There were 63 patients (12%) with moderate (Grade 2) dermatitis. In patients receiving
YERVOY 10 mg/kg in Trial 2, Grade 3-4 immune-mediated dermatitis occurred in 19 patients (4%). There were 99 patients (21%) with
moderate Grade 2 dermatitis.
Immune-mediated Neuropathies:
Immune-mediated neuropathies, including fatal cases, can occur with YERVOY. Monitor for symptoms of motor or sensory neuropathy
such as unilateral or bilateral weakness, sensory alterations, or paresthesia. Withhold YERVOY in patients with moderate neuropathy
(not interfering with daily activities). Permanently discontinue YERVOY in patients with severe neuropathy (interfering with daily
activities), such as Guillain-Barre-like syndromes. Institute medical intervention as appropriate for management for severe
neuropathy. Consider initiation of systemic corticosteroids (1-2 mg/kg/day of prednisone or equivalent) for severe neuropathies. In
patients receiving YERVOY 3 mg/kg in Trial 1, 1 case of fatal Guillain-Barré syndrome and 1 case of severe (Grade 3) peripheral
motor neuropathy were reported. Across the clinical development program of YERVOY, myasthenia gravis and additional cases of
Guillain-Barré syndrome have been reported. In patients receiving YERVOY 10 mg/kg in Trial 2, Grade 3-5 immune-mediated neuropathy
occurred in 8 patients (2%); the sole fatality was due to complications of Guillain-Barré syndrome. Moderate Grade 2
immune-mediated neuropathy occurred in 1 patient (0.2%).
Immune-mediated Endocrinopathies:
Immune-mediated endocrinopathies, including life-threatening cases, can occur with YERVOY. Monitor patients for clinical signs
and symptoms of hypophysitis, adrenal insufficiency (including adrenal crisis), and hyper- or hypothyroidism. Patients may present
with fatigue, headache, mental status changes, abdominal pain, unusual bowel habits, and hypotension, or nonspecific symptoms which
may resemble other causes such as brain metastasis or underlying disease. Unless an alternate etiology has been identified, signs
or symptoms should be considered immune-mediated. Monitor clinical chemistries, adrenocorticotropic hormone (ACTH) level, and
thyroid function tests at the start of treatment, before each dose, and as clinically indicated based on symptoms. In a limited
number of patients, hypophysitis was diagnosed by imaging studies through enlargement of the pituitary gland. Withhold YERVOY in
symptomatic patients and consider referral to an endocrinologist. Initiate systemic corticosteroids (1-2 mg/kg/day of prednisone or
equivalent) and initiate appropriate hormone replacement therapy. In patients receiving YERVOY 3 mg/kg in Trial 1, severe to
life-threatening immune-mediated endocrinopathies (requiring hospitalization, urgent medical intervention, or interfering with
activities of daily living; Grade 3-4) occurred in 9 YERVOY-treated patients (1.8%). All 9 patients had hypopituitarism, and some
had additional concomitant endocrinopathies such as adrenal insufficiency, hypogonadism, and hypothyroidism. Six of the 9 patients
were hospitalized for severe endocrinopathies. Moderate endocrinopathy (requiring hormone replacement or medical intervention;
Grade 2) occurred in 12 patients (2.3%) and consisted of hypothyroidism, adrenal insufficiency, hypopituitarism, and 1 case each of
hyperthyroidism and Cushing's syndrome. The median time to onset of moderate to severe immune-mediated endocrinopathy was 2.5
months and ranged up to 4.4 months after the initiation of YERVOY. In patients receiving YERVOY 10 mg/kg in Trial 2, Grade 3-4
immune-mediated endocrinopathies occurred in 39 patients (8%) and Grade 2 immune-mediated endocrinopathies occurred in 93 patients
(20%). Of the 39 patients with Grade 3-4 immune-mediated endocrinopathies, 35 patients had hypopituitarism (associated with 1 or
more secondary endocrinopathies, e.g., adrenal insufficiency, hypogonadism, and hypothyroidism), 3 patients had hyperthyroidism,
and 1 had primary hypothyroidism. The median time to onset of Grade 3-4 immune-mediated endocrinopathy was 2.2 months (range: 2
days-8 months). Twenty-seven (69.2%) of the 39 patients were hospitalized for immune-mediated endocrinopathies. Of the 93 patients
with Grade 2 immune-mediated endocrinopathy, 74 had primary hypopituitarism (associated with 1 or more secondary endocrinopathy,
e.g., adrenal insufficiency, hypogonadism, and hypothyroidism), 9 had primary hypothyroidism, 3 had hyperthyroidism, 3 had
thyroiditis with hypo- or hyperthyroidism, 2 had hypogonadism, 1 had both hyperthyroidism and hypopituitarism, and 1 subject
developed Graves’ ophthalmopathy. The median time to onset of Grade 2 immune-mediated endocrinopathy was 2.1 months (range: 9
days-19.3 months).
Other Immune-mediated Adverse Reactions, Including Ocular Manifestations:
Permanently discontinue YERVOY for clinically significant or severe immune-mediated adverse reactions. Initiate systemic
corticosteroids (1-2 mg/kg/day of prednisone or equivalent) for severe immune-mediated adverse reactions. Administer corticosteroid
eye drops for uveitis, iritis, or episcleritis. Permanently discontinue YERVOY for immune-mediated ocular disease unresponsive to
local immunosuppressive therapy. In Trial 1, the following clinically significant immune-mediated adverse reactions were seen in
<1% of YERVOY-treated patients: nephritis, pneumonitis, meningitis, pericarditis, uveitis, iritis, and hemolytic anemia. In
Trial 2, the following clinically significant immune-mediated adverse reactions were seen in <1% of YERVOY-treated patients
unless specified: eosinophilia (2.1%), pancreatitis (1.3%), meningitis, pneumonitis, sarcoidosis, pericarditis, uveitis and fatal
myocarditis. Across 21 dose-ranging trials administering YERVOY at doses of 0.1 to 20 mg/kg (n=2478), the following likely
immune-mediated adverse reactions were also reported with <1% incidence: angiopathy, temporal arteritis, vasculitis, polymyalgia
rheumatica, conjunctivitis, blepharitis, episcleritis, scleritis, iritis, leukocytoclastic vasculitis, erythema multiforme,
psoriasis, arthritis, autoimmune thyroiditis, neurosensory hypoacusis, autoimmune central neuropathy (encephalitis), myositis,
polymyositis, ocular myositis, hemolytic anemia, and nephritis.
Embyro-fetal Toxicity
Based on its mechanism of action, YERVOY can cause fetal harm when administered to a pregnant woman. The effects of YERVOY are
likely to be greater during the second and third trimesters of pregnancy. Advise pregnant women of the potential risk to a fetus.
Advise females of reproductive potential to use effective contraception during treatment with a YERVOY-containing regimen and for 3
months after the last dose of YERVOY.
Lactation
It is not known whether YERVOY is secreted in human milk. Advise women to discontinue nursing during treatment with YERVOY and
for 3 months following the final dose.
Common Adverse Reactions:
The most common adverse reactions (≥5%) in patients who received YERVOY at 3 mg/kg were fatigue (41%), diarrhea (32%), pruritis
(31%), rash (29%), and colitis (8%). The most common adverse reactions (≥5%) in patients who received YERVOY at 10 mg/kg were rash
(50%), diarrhea (49%), fatigue (46%), pruritus (45%), headache (33%), weight loss (32%), nausea (25%), pyrexia (18%), colitis
(16%), decreased appetite (14%), vomiting (13%), and insomnia (10%).
Please see U.S. Full Prescribing Information, including Boxed WARNING regarding immune-mediated adverse
reactions.
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. For more information about Bristol-Myers Squibb, visit us
at BMS.com or follow us on LinkedIn, Twitter, YouTube and Facebook.
Bristol-Myers Squibb Forward-Looking Statement
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform
Act of 1995 regarding the research, development and commercialization of pharmaceutical products. 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. 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, 2015 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.
Bristol-Myers Squibb Company
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