-
Pivotal Phase III studies (CheckMate -057 & -017) in both advanced
non-squamous and squamous non-small cell lung cancer in which
treatment with Opdivo demonstrated superior survival versus
chemotherapy with docetaxel in previously-treated patients, to be
disclosed
-
First pivotal Phase III trial of investigational Opdivo+Yervoy
regimen compared to Opdivo or Yervoy monotherapy in advanced melanoma,
to be presented (CheckMate -067)
-
First Phase III data for an investigational Immuno-Oncology agent
in multiple myeloma, ELOQUENT-2 results for elotuzumab, to be presented
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Breadth and depth of Immuno-Oncology portfolio showcases Opdivo and
Yervoy clinical trial results in additional tumor types, including
small-cell lung cancer, renal cell carcinoma, hepatocellular carcinoma
and glioblastoma
PRINCETON, N.J.--(BUSINESS WIRE)--
Bristol-Myers
Squibb Company (NYSE:BMY) today announced new clinical research from
three of its Immuno-Oncology agents will be presented at the 51st
Annual Meeting of the American Society of Clinical Oncology (ASCO) in
Chicago from May 29-June 2. Building on the scientific advances the
company has pioneered in Immuno-Oncology, Bristol-Myers Squibb will
present data for Opdivo and Yervoy across multiple solid
tumor types, as well as elotuzumab in relapsed or refractory multiple
myeloma.
Data to be presented at ASCO illustrate Bristol-Myers Squibb’s
commitment to developing treatment options with the potential to offer
patients with cancer the possibility of long-term survival through its
transformative Immuno-Oncology research.
Key oral data presentations include:
-
CheckMate -057, -017: First disclosure from Phase III trials
will be presented for CheckMate -057 (Late Breaking Abstract #109) and
CheckMate -017 (Abstract #8009), evaluating Opdivo in
previously-treated non-squamous and squamous non-small cell lung
cancer (NSCLC) against docetaxel therapy, respectively. Data from
CheckMate -057 will be featured in an ASCO press conference on Friday,
May 29, 1:00 - 2:00 PM CDT and presented during a Clinical Science
Symposium on Saturday, May 30 from 8:51 – 9:03 AM CDT. Data from
CheckMate -017 will be presented during an oral abstract session on
Sunday, May 31 from 4:30 – 4:42 PM CDT.
-
CheckMate -067: New Phase III research evaluating the Opdivo+Yervoy
regimen in first-line treatment of advanced melanoma (Late Breaking
Abstract #1) will be featured in an ASCO press conference on Sunday,
May 31, 8:00 – 9:00 AM CDT. These data also will be presented during
the plenary session on Sunday, May 31 from 1:35 – 1:50 PM CDT.
-
ELOQUENT-2: The first presentation of a Phase III, open-label
study (Abstract #8508) evaluating elotuzumab in combination with
lenalidomide and dexamethasone in patients with relapsed or refractory
multiple myeloma will be featured in an ASCO presscast on Wednesday,
May 13 at 12:00 PM EDT. An oral presentation of these data will take
place on Tuesday, June 2 from 9:45 – 9:57 AM CDT.
-
CA209-040: The first presentation of findings from a Phase I/II Opdivo
trial in advanced hepatocellular carcinoma (Late Breaking Abstract
#101) will be featured in an ASCO press conference on Friday, May 29,
1:00 – 2:00 PM CDT. An oral presentation of these data will take place
at a Clinical Science Symposium on Saturday, May 30 from 8:27 – 8:39
AM CDT.
“At Bristol-Myers Squibb, patients are the inspiration behind our
pioneering research in the field of Immuno-Oncology, which has led to
the approval of novel agents for the treatment of some of the hardest to
treat cancers,” said Francis Cuss, MB BChir, FRCP, executive vice
president and chief scientific officer, Bristol-Myers Squibb. “We are
proud that our revolutionary research led to the introduction of Yervoy
and Opdivo, and are excited about sharing new data at ASCO in
both solid tumors and hematologic cancers.”
The broad set of data to be presented by Bristol-Myers Squibb includes:
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Title
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Date/Time
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Lung Cancer
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Phase III, randomized trial (CheckMate -057) of nivolumab (NIVO)
versus docetaxel (DOC) in advanced non-squamous cell (non-SQ)
non-small cell lung cancer (NSCLC)
Abstract #LBA109
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Clinical Science Symposium
Saturday, May 30th
8:51
– 9:03 AM CDT
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An ongoing phase IIIb/IV safety trial of nivolumab (NIVO) in
patients (pts) with advanced or metastatic non-small-cell lung
cancer (NSCLC) who progressed after receiving 1 or more prior
systemic regimens
Abstract #3013
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Poster Discussion Session
Saturday, May 30th
3:00
– 4:15 PM CDT
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Phase I/II study of nivolumab with or without ipilimumab for
treatment of recurrent small cell lung cancer (SCLC): CA209-032
Abstract
#7503
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Oral Abstract Session
Saturday, May 30th
4:00
– 4:12 PM CDT
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A phase III study (CheckMate -017) of nivolumab (NIVO;
anti-programmed death-1 [PD-1]) vs docetaxel (DOC) in previously
treated advanced or metastatic squamous (SQ) cell non-small cell
lung cancer (NSCLC)
Abstract #8009
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Clinical Science Symposium
Sunday, May 31st
4:30
– 4:42 PM CDT
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First-line monotherapy with nivolumab (NIVO; anti-programmed
death-1 [PD-1]) in advanced non-small cell lung cancer (NSCLC):
Safety, Efficacy and correlation of outcomes with PD-1 ligand
(PD-L1) expression
Abstract #8025
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Poster Session
Monday, June 1st
8:00 – 11:30
AM CDT
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Phase II studies of nivolumab (anti-PD-1, BMS-936558, ONO-4538) in
patients with advanced squamous (sq) or nonsquamous (non-sq)
non-small cell lung cancer (NSCLC)
Abstract #8027
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Poster Session
Monday, June 1st
8:00 – 11:30
AM CDT
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Melanoma
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Clinical response, progression-free survival (PFS), and safety in
patients (pts) with advanced melanoma (MEL) receiving nivolumab
(NIVO) combined with ipilimumab (IPI) vs IPI monotherapy in
CheckMate -069 study
Abstract #9004
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Oral Abstract Session
Saturday, May 30th
2:27
– 2:39 PM CDT
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Efficacy and safety results from a phase III trial of nivolumab
(NIVO) alone or combined with ipilimumab (IPI) versus IPI alone in
treatment-naïve patients (pts) with advanced melanoma (MEL)
(CheckMate -067)
Abstract #LBA1
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Plenary Session
Sunday, May 31st
1:35 – 1:50
PM CDT
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Effect of nivolumab (NIVO) on quality of life (QoL) in patients
(pts) with treatment-naïve advanced melanoma (MEL): Results of a
phase III study (CheckMate -066)
Abstract #9027
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Poster Session
Monday, June 1st
1:15 – 4:45
PM CDT
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Effect of nivolumab (NIVO) in combination with ipilimumab (IPI)
versus IPI alone on quality of life (QoL) in patients (pts) with
treatment-naïve advanced melanoma (MEL): Results of a phase II
study (CheckMate -069)
Abstract #9029
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Poster Session
Monday, June 1st
1:15 – 4:45
PM CDT
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A single-arm, open-label, phase II study to evaluate the safety of
vemurafenib (VEM) followed by ipilimumab (IPI) in BRAF
V600-mutated metastatic melanoma (MM)
Abstract #9032
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Poster Session
Monday, June 1st
1:15 – 4:45
PM CDT
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Safety profile of nivolumab (NIVO) in patients (pts) with advanced
melanoma (MEL): A pooled analysis
Abstract #9018
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Poster Discussion Session
Monday, June 1st
4:45
– 6:00 PM CDT
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Hematology
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A randomized phase II study of bortezomib (Btz)/dexamethasone
(dex) with or without elotuzumab (Elo) in patients with
relapsed/refractory multiple myeloma (RRMM)
Abstract #8573
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Poster Sesssion
Sunday, May 31st
8:00 – 11:30
AM CDT
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ELOQUENT-2: A phase III, randomized, open-label study of
lenalidomide (Len)/dexamethasone (dex) with/without elotuzumab
(Elo) in patients (pts) with relapsed/refractory multiple myeloma
(RRMM)
Abstract #8508
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Oral Abstract Session
Tuesday, June 2nd
9:45
– 9:57 AM CDT
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Hepatocellular Carcinoma, Glioblastoma, and Renal Cell Carcinoma
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Phase I/II safety and antitumor activity of nivolumab in patients
with advanced hepatocellular carcinoma (HCC): CA209-040
Abstract
#LBA101
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Clinical Science Symposium
Saturday, May 30th
8:27
– 8:39 AM CDT
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Preliminary safety and activity of nivolumab and its combination
with ipilimumab in recurrent glioblastoma (GBM): CheckMate -143
Abstract
#3010
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Poster Discussion Session
Saturday, May 30th
3:00
– 4:15 PM CDT
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Immunomodulatory activity of nivolumab in metastatic renal cell
carcinoma (mRCC): Association of biomarkers with clinical outcomes
Abstract
#4500
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Oral Abstract Session
Monday, June 1st
9:45 –
9:57 AM CDT
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Expanded cohort results from CheckMate -016: A phase I study of
nivolumab in combination with ipilimumab in metastatic renal cell
carcinoma (mRCC)
Abstract #4516
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Poster Discussion Session
Monday, June 1st
4:45
– 6:00 PM CDT
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Analysis of real world treatment compliance in a cohort of 2,395
patients with metastatic renal cell carcinoma (mRCC)
Abstract
#4546
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Poster Session
Monday, June 1st
1:15 – 4:45
PM CDT
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Updated survival results from a randomized, dose-ranging phase II
study of nivolumab (NIVO) in metastatic renal cell carcinoma (mRCC)
Abstract
#4553
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Poster Session
Monday, June 1st
1:15 – 4:45
PM CDT
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About Elotuzumab
Elotuzumab is an investigational Immuno-Oncology (more specifically
defined as immuno-stimulatory) antibody targeted against Signaling
Lymphocyte Activation Molecule (SLAMF7), a cell-surface glycoprotein
that is highly and uniformly expressed on myeloma cells and Natural
Killer (NK) cells but is not detected on normal solid tissues or on
hematopoietic stem cells. Elotuzumab is being investigated to determine
whether the compound may selectively target myeloma cells. It is
believed that elotuzumab works through a dual mechanism of action:
binding to SLAMF7 on NK cells, directly activating them and binding to
SLAMF7 on myeloma cells, flagging them for NK cell recognition and
destruction.
In May 2014, the U.S. Food and Drug Administration (FDA) granted
elotuzumab Breakthrough Therapy Designation for use in combination with
one of the chemotherapy treatments for multiple myeloma (lenalidomide,
used in combination with dexamethasone) in patients who have received
one or more prior treatments. Elotuzumab is an investigational compound
and its safety and efficacy have not been evaluated by the FDA or any
other health authority.
Bristol-Myers Squibb and AbbVie are co-developing elotuzumab, with
Bristol-Myers Squibb leading the commercialization of the agent.
OPDIVO (nivolumab) IMPORTANT SAFETY INFORMATION
Immune-Mediated Pneumonitis
-
Severe pneumonitis or interstitial lung disease, including fatal
cases, occurred with OPDIVO treatment. Across the clinical trial
experience in 691 patients with solid tumors, fatal immune-mediated
pneumonitis occurred in 0.7% (5/691) of patients receiving OPDIVO; no
cases occurred in Trial 1 or Trial 3. In Trial 1, pneumonitis,
including interstitial lung disease, occurred in 3.4% (9/268) of
patients receiving OPDIVO and none of the 102 patients receiving
chemotherapy. Immune-mediated pneumonitis occurred in 2.2% (6/268) of
patients receiving OPDIVO; one with Grade 3 and five with Grade 2. In
Trial 3, immune-mediated pneumonitis occurred in 6% (7/117) of
patients receiving OPDIVO, including, five Grade 3 and two Grade 2
cases. Monitor patients for signs and symptoms of pneumonitis.
Administer corticosteroids for Grade 2 or greater pneumonitis.
Permanently discontinue OPDIVO for Grade 3 or 4 and withhold OPDIVO
until resolution for Grade 2.
Immune-Mediated Colitis
-
In Trial 1, diarrhea or colitis occurred in 21% (57/268) of patients
receiving OPDIVO and 18% (18/102) of patients receiving chemotherapy.
Immune-mediated colitis occurred in 2.2% (6/268) of patients receiving
OPDIVO; five with Grade 3 and one with Grade 2. In Trial 3, diarrhea
occurred in 21% (24/117) of patients receiving OPDIVO. Grade 3
immune-mediated colitis occurred in 0.9% (1/117) of patients. Monitor
patients for immune-mediated colitis. Administer corticosteroids for
Grade 2 (of more than 5 days duration), 3, or 4 colitis. Withhold
OPDIVO for Grade 2 or 3. Permanently discontinue OPDIVO for Grade 4
colitis or recurrent colitis upon restarting OPDIVO.
Immune-Mediated Hepatitis
-
In Trial 1, there was an increased incidence of liver test
abnormalities in the OPDIVO-treated group as compared to the
chemotherapy-treated group, with increases in AST (28% vs 12%),
alkaline phosphatase (22% vs 13%), ALT (16% vs 5%), and total
bilirubin (9% vs 0). Immune-mediated hepatitis occurred in 1.1%
(3/268) of patients receiving OPDIVO; two with Grade 3 and one with
Grade 2. In Trial 3, the incidences of increased liver test values
were AST (16%), alkaline phosphatase (14%), ALT (12%), and total
bilirubin (2.7%). Monitor patients for abnormal liver tests prior to
and periodically during treatment. Administer corticosteroids for
Grade 2 or greater transaminase elevations. Withhold OPDIVO for Grade
2 and permanently discontinue OPDIVO for Grade 3 or 4 immune-mediated
hepatitis.
Immune-Mediated Nephritis and Renal Dysfunction
-
In Trial 1, there was an increased incidence of elevated creatinine in
the OPDIVO-treated group as compared to the chemotherapy-treated group
(13% vs 9%). Grade 2 or 3 immune-mediated nephritis or renal
dysfunction occurred in 0.7% (2/268) of patients. In Trial 3, the
incidence of elevated creatinine was 22%. Immune-mediated renal
dysfunction (Grade 2) occurred in 0.9% (1/117) of patients. Monitor
patients for elevated serum creatinine prior to and periodically
during treatment. For Grade 2 or 3 serum creatinine elevation,
withhold OPDIVO and administer corticosteroids; if worsening or no
improvement occurs, permanently discontinue OPDIVO. Administer
corticosteroids for Grade 4 serum creatinine elevation and permanently
discontinue OPDIVO.
Immune-Mediated Hypothyroidism and Hyperthyroidism
-
In Trial 1, Grade 1 or 2 hypothyroidism occurred in 8% (21/268) of
patients receiving OPDIVO and none of the 102 patients receiving
chemotherapy. Grade 1 or 2 hyperthyroidism occurred in 3% (8/268) of
patients receiving OPDIVO and 1% (1/102) of patients receiving
chemotherapy. In Trial 3, hypothyroidism occurred in 4.3% (5/117) of
patients receiving OPDIVO. Hyperthyroidism occurred in 1.7% (2/117) of
patients, including one Grade 2 case. Monitor thyroid function prior
to and periodically during treatment. Administer hormone replacement
therapy for hypothyroidism. Initiate medical management for control of
hyperthyroidism.
Other Immune-Mediated Adverse Reactions
-
In Trial 1 and 3 (n=385), the following clinically significant
immune-mediated adverse reactions occurred in <2% of OPDIVO-treated
patients: adrenal insufficiency, uveitis, pancreatitis, facial and
abducens nerve paresis, demyeliniation, autoimmune neuropathy, motor
dysfunction, and vasculitis. Across clinical trials of OPDIVO
administered at doses 3 mg/kg and 10 mg/kg, additional clinically
significant, immune-mediated adverse reactions were identified:
hypophysitis, diabetic ketoacidosis, hypopituitarism, Guillain-Barré
syndrome, and myasthenic syndrome. Based on the severity of adverse
reaction, withhold OPDIVO, administer high-dose corticosteroids, and,
if appropriate, initiate hormone- replacement therapy.
Embryofetal Toxicity
-
Based on its mechanism of action, OPDIVO can cause fetal harm when
administered to a pregnant woman. Advise pregnant women of the
potential risk to a fetus. Advise females of reproductive potential to
use effective contraception during treatment with OPDIVO and for at
least 5 months after the last dose of OPDIVO.
Lactation
-
It is not known whether OPDIVO is present in human milk. Because many
drugs, including antibodies, are excreted in human milk and because of
the potential for serious adverse reactions in nursing infants from
OPDIVO, advise women to discontinue breastfeeding during treatment.
Serious Adverse Reactions
-
In Trial 1, serious adverse reactions occurred in 41% of patients
receiving OPDIVO. Grade 3 and 4 adverse reactions occurred in 42% of
patients receiving OPDIVO. The most frequent Grade 3 and 4 adverse
drug reactions reported in 2% to <5% of patients receiving OPDIVO were
abdominal pain, hyponatremia, increased aspartate aminotransferase,
and increased lipase.
-
In Trial 3, serious adverse reactions occurred in 59% of patients
receiving OPDIVO. The most frequent serious adverse drug reactions
reported in =2% of patients were dyspnea, pneumonia, chronic
obstructive pulmonary disease exacerbation, pneumonitis,
hypercalcemia, pleural effusion, hemoptysis, and pain.
Common Adverse Reactions
-
The most common adverse reactions (=20%) reported with OPDIVO in Trial
1 were rash (21%) and in Trial 3 were fatigue (50%), dyspnea (38%),
musculoskeletal pain (36%), decreased appetite (35%), cough (32%),
nausea (29%), and constipation (24%).
Please see US
Full Prescribing Information for OPDIVO.
YERVOY® (ipilimumab) INDICATION & IMPORTANT
SAFETY INFORMATION
YERVOY (ipilimumab) is indicated for the treatment of unresectable or
metastatic melanoma.
Important Safety Information
WARNING: IMMUNE-MEDIATED ADVERSE REACTIONS
YERVOY can result in severe and fatal immune-mediated adverse
reactions due to T-cell activation and proliferation. 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.
Assess patients for signs and symptoms of enterocolitis, dermatitis,
neuropathy, and endocrinopathy and evaluate clinical chemistries
including liver function tests (LFTs) and thyroid function tests at
baseline and before each dose.
Permanently discontinue YERVOY and initiate systemic high-dose
corticosteroids for severe immune-mediated reactions.
Recommended Dose Modifications
Withhold dose for any moderate immune-mediated adverse reactions or for
symptomatic endocrinopathy until return to baseline, improvement to mild
severity, or complete resolution, and patient is receiving <7.5 mg
prednisone or equivalent per day.
Permanently discontinue YERVOY for any of the following:
-
Persistent moderate adverse reactions or inability to reduce
corticosteroid dose to 7.5 mg prednisone or equivalent per day
-
Failure to complete full treatment course within 16 weeks from
administration of first dose
-
Severe or life-threatening adverse reactions, including any of the
following:
-
Colitis with abdominal pain, fever, ileus, or peritoneal signs;
increase in stool frequency (=7 over baseline), stool
incontinence, need for intravenous hydration for >24 hours,
gastrointestinal hemorrhage, and gastrointestinal perforation
-
AST or ALT >5 × the upper limit of normal (ULN) or total bilirubin
>3 × the ULN
-
Stevens-Johnson syndrome, toxic epidermal necrolysis, or rash
complicated by full-thickness dermal ulceration or necrotic,
bullous, or hemorrhagic manifestations
-
Severe motor or sensory neuropathy, Guillain-Barré syndrome, or
myasthenia gravis
-
Severe immune-mediated reactions involving any organ system
-
Immune-mediated ocular disease which is unresponsive to topical
immunosuppressive therapy
Immune-mediated Enterocolitis:
-
In the pivotal Phase 3 study in YERVOY-treated patients, severe,
life-threatening, or fatal (diarrhea of =7 stools above baseline,
fever, ileus, peritoneal signs; Grade 3-5) immune-mediated
enterocolitis occurred in 34 (7%) and moderate (diarrhea with up to 6
stools above baseline, abdominal pain, mucus or blood in stool; Grade
2) enterocolitis occurred in 28 (5%) patients
-
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 of 62 (8%) patients with moderate,
severe, or life-threatening immune-mediated enterocolitis following
inadequate response to corticosteroids
-
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
-
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
-
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)
Immune-mediated Hepatitis:
-
In the pivotal Phase 3 study in YERVOY-treated patients, severe,
life-threatening, or fatal hepatotoxicity (AST or ALT elevations >5x
the ULN or total bilirubin elevations >3x the ULN; Grade 3–5) occurred
in 8 (2%) patients, with fatal hepatic failure in 0.2% and
hospitalization in 0.4%
-
13 (2.5%) additional YERVOY-treated patients experienced moderate
hepatotoxicity manifested by LFT abnormalities (AST or ALT elevations
>2.5x but =5x the ULN or total bilirubin elevation >1.5x but =3x the
ULN; Grade 2)
-
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
-
Permanently discontinue YERVOY in patients with Grade 3-5
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
-
Withhold YERVOY in patients with Grade 2 hepatotoxicity
-
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)
Immune-mediated Dermatitis:
-
In the pivotal Phase 3 study in YERVOY-treated patients, 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 (2.5%)
patients
-
1 (0.2%) patient died as a result of toxic epidermal necrolysis
-
1 additional patient required hospitalization for severe dermatitis
-
There were 63 (12%) YERVOY-treated patients with moderate (Grade 2)
dermatitis
-
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
-
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. Withhold YERVOY in
patients with moderate to severe signs and symptoms
-
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
Immune-mediated Neuropathies:
-
In the pivotal Phase 3 study in YERVOY-treated patients, 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
-
Monitor for symptoms of motor or sensory neuropathy such as unilateral
or bilateral weakness, sensory alterations, or paresthesia.
Permanently discontinue YERVOY in patients with severe neuropathy
(interfering with daily activities) such as Guillain-Barré–like
syndromes
-
Institute medical intervention as appropriate for management of severe
neuropathy. Consider initiation of systemic corticosteroids (1-2
mg/kg/day of prednisone or equivalent) for severe neuropathies.
Withhold YERVOY in patients with moderate neuropathy (not interfering
with daily activities)
Immune-mediated Endocrinopathies:
-
In the pivotal Phase 3 study in YERVOY- treated patients, 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 (1.8%) patients
-
All 9 patients had hypopituitarism, and some had additional
concomitant endocrinopathies such as adrenal insufficiency,
hypogonadism, and hypothyroidism
-
6 of the 9 patients were hospitalized for severe endocrinopathies
-
Moderate endocrinopathy (requiring hormone replacement or medical
intervention; Grade 2) occurred in 12 (2.3%) YERVOY-treated patients
and consisted of hypothyroidism, adrenal insufficiency,
hypopituitarism, and 1 case each of hyperthyroidism and Cushing’s
syndrome
-
Median time to onset of moderate to severe immune-mediated
endocrinopathy was 11 weeks and ranged up to 19.3 weeks after the
initiation of 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 thyroid function tests and clinical chemistries 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. Initiate systemic
corticosteroids (1-2 mg/kg/day of prednisone or equivalent) and
initiate appropriate hormone replacement therapy. Long-term hormone
replacement therapy may be necessary
Other Immune-mediated Adverse Reactions, Including Ocular
Manifestations:
-
In the pivotal Phase 3 study in YERVOY-treated patients, clinically
significant immune-mediated adverse reactions seen in <1% were:
nephritis, pneumonitis, meningitis, pericarditis, uveitis, iritis, and
hemolytic anemia
-
Across the clinical development program for YERVOY, likely
immune-mediated adverse reactions also reported with <1% incidence
were: myocarditis, angiopathy, temporal arteritis, vasculitis,
polymyalgia rheumatica, conjunctivitis, blepharitis, episcleritis,
scleritis, leukocytoclastic vasculitis, erythema multiforme,
psoriasis, pancreatitis, arthritis, autoimmune thyroiditis,
sarcoidosis, neurosensory hypoacusis, autoimmune central neuropathy
(encephalitis), myositis, polymyositis, and ocular myositis
-
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
Pregnancy & Nursing:
-
YERVOY is classified as pregnancy category C. There are no adequate
and well-controlled studies of YERVOY in pregnant women. Use YERVOY
during pregnancy only if the potential benefit justifies the potential
risk to the fetus
-
Human IgG1 is known to cross the placental barrier and YERVOY is an
IgG1; therefore, YERVOY has the potential to be transmitted from the
mother to the developing fetus
-
It is not known whether YERVOY is secreted in human milk. Because many
drugs are secreted in human milk and because of the potential for
serious adverse reactions in nursing infants from YERVOY, a decision
should be made whether to discontinue nursing or to discontinue YERVOY
Common Adverse Reactions:
-
The most common adverse reactions (=5%) in patients who received
YERVOY at 3 mg/kg were fatigue (41%), diarrhea (32%), pruritus (31%),
rash (29%), and colitis (8%)
Please see Full Prescribing Information, including Boxed WARNING
regarding immune-mediated adverse reactions, available at www.bms.com.
Yervoy is a registered trademark of Bristol-Myers Squibb Company.
Immuno-Oncology at Bristol-Myers Squibb
Surgery, radiation, cytotoxic or targeted therapies have represented the
mainstay of cancer treatment over the last several decades, but
long-term survival and a positive quality of life have remained elusive
for many patients with advanced disease.
To address this unmet medical need, Bristol-Myers Squibb is leading
research in an innovative field of cancer research and treatment known
as Immuno-Oncology, which involves agents whose primary mechanism is to
work directly with the body’s immune system to fight cancer. The company
is exploring a variety of compounds and immunotherapeutic approaches for
patients with different types of cancer, including researching the
potential of combining Immuno-Oncology agents that target different
pathways in the treatment of cancer.
Bristol-Myers Squibb is committed to advancing the science of
Immuno-Oncology, with the goal of changing survival expectations and the
way patients live with cancer.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global pharmaceutical 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 www.bms.com,
or follow us on Twitter at http://twitter.com/bmsnews.
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.
Among other risks, there can be no guarantee that the investigational
compounds and products described in this release will receive regulatory
approval for the indications described here, or if approved, will become
commercially successful. 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, 2014 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.

Source: Bristol-Myers Squibb Company