The first and only PD-1 inhibitor approved
based on a demonstrated OS benefit in patients with advanced RCC
who have received prior anti-angiogenic therapy1
Approval based on CheckMate -025, which
demonstrated median OS benefit of 25 months (95% CI: 21.7-NE)
for Opdivo vs. 19.6 months (95% CI: 17.6-23.1) for
everolimus (HR: 0.73; [95% CI: 0.60-0.89;
p=0.0018])1,2
With this fifth approval for Opdivo
in 12 months, in a third distinct tumor type, more patients with
cancer now have access to an Immuno-Oncology treatment
option1
Bristol-Myers Squibb Company (NYSE:BMY) today announced that the
U.S. Food and Drug Administration (FDA) has approved Opdivo
(nivolumab) injection, for intravenous use, for the treatment of
patients with advanced renal cell carcinoma (RCC) who have received
prior anti-angiogenic therapy.1 Today’s announcement marks the
approval of the first and only PD-1 inhibitor to deliver
significant overall survival (OS) in patients with advanced RCC who
have received prior anti-angiogenic therapy.1 In the CheckMate -025
trial, patients treated with Opdivo achieved a median OS of 25
months (95% CI: 21.7-not estimable [NE]) versus 19.6 months (95%
CI: 17.6-23.1) for everolimus, a current standard of care (SOC) in
this patient population (hazard ratio [HR]: 0.73; [95% CI:
0.60-0.89; p=0.0018]), based on a prespecified interim analysis.1,2
In the study, the safety profile was consistent with prior Opdivo
studies.2
“This is the fifth approval for Opdivo across three distinct
tumor types. This latest approval reflects our commitment to
delivering on our promise to provide cancer patients with a
potential for long-term survival,” said Francis Cuss, MB BChir,
FRCP, executive vice president and chief scientific officer at
Bristol-Myers Squibb. “We believe our pioneering approach to
Immuno-Oncology is driving change in how cancer may be
treated.”
Opdivo is associated with immune-mediated: pneumonitis, colitis,
hepatitis, endocrinopathies, nephritis and renal dysfunction, rash,
encephalitis, other adverse reactions; infusion reactions; and
embryofetal toxicity. Please see the Important Safety Information
section below.1
The U.S. approval was based on data from CheckMate -025, an
open-label, randomized Phase 3 study which demonstrated a median OS
benefit of 25 months (95% CI: 21.7-NE) compared with 19.6 months
(95% CI: 17.6-23.1) for everolimus (HR: 0.73; [95% CI: 0.60-0.89;
p=0.0018]).1,2 This is the first time an immune checkpoint
inhibitor has delivered a significant survival benefit in this
patient population.1 On September 16, 2015, the FDA granted
Breakthrough Therapy Designation to Opdivo for advanced RCC
patients treated with prior anti-angiogenic therapy, also based on
positive results from the CheckMate -025 study, reinforcing the
unmet need in the treatment of RCC.2
“As an Immuno-Oncology agent that works directly with the body’s
immune system, Opdivo offers a new approach for physicians to use
when treating patients with advanced renal cell carcinoma who have
received prior anti-angiogenic therapy,” continued Cuss. “For the
first time, these patients have a PD-1 inhibitor treatment option,
which has the potential to provide an unprecedented survival
advantage compared to a standard of care.”
Proven Significant Overall Survival vs.
a Standard of Care
CheckMate -025 is a landmark, open-label, randomized Phase 3
study, evaluating Opdivo compared to an active comparator
(everolimus) in patients with advanced RCC who have received prior
anti-angiogenic therapy.1,2 Clinical results from CheckMate -025
were recently presented at the 2015 European Cancer Congress with
simultaneous publication in The New England Journal of
Medicine.2
In CheckMate -025, 821 patients were randomized to receive
Opdivo (3 mg/kg administered intravenously every two weeks; n=410)
compared to a SOC (everolimus, 10 mg administered orally daily;
n=411).1,2 The primary endpoint was OS.1,2 Objective response rate
(ORR) was evaluated as a secondary endpoint.1,2 The prespecified
interim analysis was conducted when 398 events were observed (70%
of the planned number of events for final analysis).1 In this
trial, Opdivo demonstrated a median OS of 25 months (95% CI:
21.7-NE) versus 19.6 months (95% CI: 17.6-23.1) for everolimus (HR:
0.73; [95% CI: 0.60-0.89; p=0.0018]), offering a 5.4 month survival
benefit.1 With Opdivo, the OS benefit was observed independent of
PD-L1 expression.1 In addition to improving survival, Opdivo
demonstrated a superior ORR compared to everolimus (21.5%; 95% CI:
17.6–25.80 vs. 3.9%; 95% CI: 2.2–6.2) with a higher median duration
of response (23.0 months; 95% CI: 12.0-NE vs. 13.7 months; 95% CI:
8.3-21.9).1
“Results from CheckMate -025 mark the first time an
Immuno-Oncology treatment has demonstrated a survival advantage in
patients with advanced renal cell carcinoma compared to a standard
of care in this population,” said Robert J. Motzer, M.D., medical
oncologist, Memorial Sloan Kettering Cancer Center. “For patients
with advanced renal cell carcinoma, treatment options are limited
and new approaches that extend survival are desperately needed.
With the FDA approval of Opdivo, the kidney cancer community is now
a step closer toward achieving long-term survival, which has
remained elusive for many patients. This represents a true shift in
our treatment paradigm.”
While the treatment landscape for RCC has improved over the last
decade, patients are in need of new treatment options that
demonstrate longer-term effects and overall survival benefits.3
“This approval of Opdivo represents a major milestone for the
kidney cancer community,” said William P. Bro, chief executive
officer and patient coordinator, Kidney Cancer Association. “We
thank Bristol-Myers Squibb and the FDA for working swiftly to bring
this important new treatment option and potential for extended
survival to patients.”
The safety profile of Opdivo in CheckMate -025 was consistent
with prior studies.2 Serious adverse events occurred in 47% of
patients receiving Opdivo.1 The most frequent serious adverse
reactions reported in at least 2% of patients receiving Opdivo were
acute kidney injury, pleural effusion, pneumonia, diarrhea, and
hypercalcemia.1 In the study, the most common adverse reactions
(≥20%) reported in patients receiving Opdivo versus everolimus were
asthenic conditions (56% vs. 57%), cough (34% vs. 38%), nausea (28%
vs. 29%), rash (28% vs. 36%), dyspnea (27% vs. 31%), diarrhea (25%
vs. 32%), constipation (23% vs. 18%), decreased appetite (23% vs.
30%), back pain (21% vs. 16%), and arthralgia (20% vs. 14%).1
About Renal Cell
Carcinoma
Renal cell carcinoma (RCC) is the most common type of kidney
cancer in the U.S., accounting for approximately 9 out of 10 kidney
cancers.3 An estimated 61,560 new cases of kidney cancer will be
diagnosed in 2015 in the U.S., and the disease is more common in
men than women.3 Clear-cell RCC is the most prevalent type of
RCC, which includes 70% of all cases.3 Approximately 14,000 people
will die from kidney cancer in the U.S. in 2015 and the five-year
survival rate for patients diagnosed with advanced kidney cancer is
8%.3
Leading Immuno-Oncology Development in
Renal Cell Carcinoma
Bristol-Myers Squibb is a pioneer in the 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.
Opdivo is a programmed death-1 (PD-1) immune checkpoint
inhibitor, and works by targeting the immune system through the
PD-1 immune checkpoint pathway.1 Targeting the immune system
through this pathway is now recognized as a new approach to RCC
treatment.3
Bristol-Myers Squibb has a broad, global development program to
study Opdivo in multiple tumor types consisting of more than 50
trials – as a monotherapy or in combination with other therapies –
in which more than 8,000 patients have been enrolled worldwide.
About Bristol-Myers Squibb’s Patient
Support Programs
Bristol-Myers Squibb remains committed to helping patients
access our medicines. For support and assistance, patients and
physicians may call 1-855-OPDIVO-1. This number offers one-stop
access to a range of support services for patients and healthcare
professionals alike.
About Bristol-Myers Squibb’s Access
Support
Bristol-Myers Squibb is committed to helping patients access
Opdivo and offers BMS Access Support® to support patients and
providers in gaining access. BMS Access Support, the Bristol-Myers
Squibb Reimbursement Services program, is designed to support
access to BMS medicines and expedite time to therapy through
reimbursement support including Benefit Investigations, Prior
Authorization Facilitation, Appeals Assistance, and assistance for
patient out-of-pocket costs. BMS Access Support assists patients
and providers throughout the treatment journey – whether it is at
initial diagnosis or in support of transition from a clinical
trial. More information about our reimbursement support services
can be obtained by calling 1-800-861-0048 or by visiting
www.bmsaccesssupport.com. For healthcare providers seeking specific
reimbursement information, please visit the BMS Access Support
Product section by visiting www.bmsaccesssupportopdivo.com.
INDICATIONS
OPDIVO® is indicated for the treatment of patients with advanced
renal cell carcinoma (RCC) who have received prior anti-angiogenic
therapy.
OPDIVO® as a single agent is indicated for the treatment of
patients with unresectable or metastatic melanoma and disease
progression following ipilimumab and, if BRAF V600 mutation
positive, a BRAF inhibitor. This indication is approved under
accelerated approval based on tumor response rate and durability of
response. Continued approval for this indication may be contingent
upon verification and description of clinical benefit in
confirmatory trials.
OPDIVO®, in combination with ipilimumab, is indicated for the
treatment of patients with BRAF V600 wild-type, unresectable or
metastatic melanoma. This indication is approved under accelerated
approval based on tumor response rate and durability of response.
Continued approval for this indication may be contingent upon
verification and description of clinical benefit in confirmatory
trials.
OPDIVO® is indicated for the treatment of patients with
metastatic non small cell lung cancer (NSCLC) with progression on
or after platinum-based chemotherapy. Patients with EGFR or ALK
genomic tumor aberrations should have disease progression on
FDA-approved therapy for these aberrations prior to receiving
OPDIVO®.
IMPORTANT SAFETY
INFORMATION
WARNING: IMMUNE-MEDIATED ADVERSE REACTIONS
YERVOY 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.
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.
Permanently discontinue YERVOY and initiate systemic
high-dose corticosteroid therapy for severe immune-mediated
reactions.
Immune-Mediated Pneumonitis
Immune-mediated pneumonitis or interstitial lung disease,
including fatal cases, occurred with OPDIVO treatment. Across the
clinical trial experience with solid tumors, fatal immune-mediated
pneumonitis occurred with OPDIVO. In Checkmate 069, there were six
additional patients who died without resolution of abnormal
respiratory findings. Monitor patients for signs with radiographic
imaging and symptoms of pneumonitis. Administer corticosteroids for
Grade 2 or greater pneumonitis. Permanently discontinue for Grade 3
or 4 and withhold until resolution for Grade 2. In Checkmate 037,
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: Grade 3 (n=1) and Grade
2 (n=5). In Checkmate 057, immune-mediated pneumonitis, including
interstitial lung disease, occurred in 3.4% (10/287) of patients:
Grade 3 (n=5), Grade 2 (n=2), and Grade 1 (n=3). In Checkmate 025,
pneumonitis, including interstitial lung disease, occurred in 5.2%
(21/406) of patients receiving OPDIVO and 18.4% (73/397) of
patients receiving everolimus. Immune-mediated pneumonitis occurred
in 4.4% (18/406) of patients receiving OPDIVO: Grade 4 (n=1), Grade
3 (n=4), Grade 2 (n=12), and Grade 1 (n=1). In Checkmate 069,
pneumonitis, including interstitial lung disease, occurred in 10%
(9/94) of patients receiving OPDIVO in combination with YERVOY and
2.2% (1/46) of patients receiving YERVOY. Immune-mediated
pneumonitis occurred in 6% (6/94) of patients receiving OPDIVO in
combination with YERVOY: Grade 5 (n=1), Grade 3 (n=2) and Grade 2
(n=3).
Immune-Mediated Colitis
Immune-mediated colitis can occur with OPDIVO treatment. Monitor
patients for signs and symptoms of colitis. Administer
corticosteroids for Grade 2 (of more than 5 days duration), 3, or 4
colitis. As a single agent, withhold OPDIVO for Grade 2 or 3 and
permanently discontinue for Grade 4 or recurrent colitis upon
restarting OPDIVO. In combination with YERVOY, withhold OPDIVO for
Grade 2 and permanently discontinue for Grade 3 or 4 or recurrent
colitis upon restarting OPDIVO. In Checkmate 037, 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;
Grade 3 (n=5) and Grade 2 (n=1). In Checkmate 057, diarrhea or
colitis occurred in 17% (50/287) of patients receiving OPDIVO.
Immune-mediated colitis occurred in 2.4% (7/287) of patients: Grade
3 (n=3), Grade 2 (n=2), and Grade 1 (n=2). In Checkmate 025,
diarrhea or colitis occurred in 25% (100/406) of patients receiving
OPDIVO and 32% (126/397) of patients receiving everolimus.
Immune-mediated diarrhea or colitis occurred in 3.2% (13/406) of
patients receiving OPDIVO: Grade 3 (n=5), Grade 2 (n=7), and Grade
1 (n=1). In Checkmate 069, diarrhea or colitis occurred in 57%
(54/94) of patients receiving OPDIVO in combination with YERVOY and
46% (21/46) of patients receiving YERVOY. Immune-mediated colitis
occurred in 33% (31/94) of patients receiving OPDIVO in combination
with YERVOY: Grade 4 (n=1), Grade 3 (n=16), Grade 2 (n=9), and
Grade 1 (n=5).
In a separate Phase 3 study of YERVOY 3 mg/kg, 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%) patients. Across all
YERVOY-treated patients in that study (n=511), 5 (1%) developed
intestinal perforation, 4 (0.8%) died as a result of complications,
and 26 (5%) were hospitalized for severe enterocolitis.
Immune-Mediated Hepatitis
Immune-mediated hepatitis can occur with OPDIVO treatment.
Monitor patients for abnormal liver tests prior to and periodically
during treatment. Administer corticosteroids for Grade 2 or greater
transaminase elevations. Withhold for Grade 2 and permanently
discontinue for Grade 3 or 4 immune-mediated hepatitis. In
Checkmate 037, 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; Grade 3 (n=2) and Grade 2
(n=1). In Checkmate 057, one patient (0.3%) developed
immune-mediated hepatitis. In Checkmate 025, there was an increased
incidence of liver test abnormalities compared to baseline in AST
(33% vs 39%), alkaline phosphatase (32% vs 32%), ALT (22% vs 31%),
and total bilirubin (9% vs 3%) in the OPDIVO-treated and
everolimus-treated groups, respectively. Immune-mediated hepatitis
requiring systemic immunosuppression occurred in 1.5% (6/406) of
patients receiving OPDIVO: Grade 3 (n=5) and Grade 2 (n=1). In
Checkmate 069, immune-mediated hepatitis occurred in 15% (14/94) of
patients receiving OPDIVO in combination with YERVOY: Grade 4
(n=3), Grade 3 (n=9), and Grade 2 (n=2).
In a separate Phase 3 study of YERVOY 3 mg/kg, 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%.
Immune-Mediated Dermatitis
In a separate Phase 3 study of YERVOY 3 mg/kg, severe,
life-threatening, or fatal immune-mediated dermatitis (eg,
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.
Immune-Mediated Neuropathies
In a separate Phase 3 study of YERVOY 3 mg/kg, 1 case of fatal
Guillain-Barré syndrome and 1 case of severe (Grade 3) peripheral
motor neuropathy were reported.
Immune-Mediated Endocrinopathies
Hypophysitis, adrenal insufficiency, thyroid disorders, and type
I diabetes mellitus can occur with OPDIVO treatment. Monitor
patients for signs and symptoms of hypophysitis, signs and symptoms
of adrenal insufficiency during and after treatment, thyroid
function prior to and periodically during treatment, and
hyperglycemia. Administer corticosteroids for Grade 2 or greater
hypophysitis. Withhold for Grade 2 or 3 and permanently discontinue
for Grade 4 hypophysitis. Administer corticosteroids for Grade 3 or
4 adrenal insufficiency. Withhold for Grade 2 and permanently
discontinue for Grade 3 or 4 adrenal insufficiency. Administer
hormone replacement therapy for hypothyroidism. Initiate medical
management for control of hyperthyroidism. Administer insulin for
type I diabetes. Withhold OPDIVO for Grade 3 and permanently
discontinue for Grade 4 hyperglycemia.
In Checkmate 025, hypophysitis occurred in 0.5% (2/406) of
patients receiving OPDIVO: Grade 3 (n=1) and Grade 1 (n=1). In
Checkmate 069, hypophysitis occurred in 13% (12/94) of patients
receiving OPDIVO in combination with YERVOY: Grade 3 (n=2) and
Grade 2 (n=10). In Checkmate 037 and 057 (n=555), adrenal
insufficiency occurred in 1% of patients receiving OPDIVO. In
Checkmate 025, adrenal insufficiency occurred in 2% (8/406) of
patients receiving OPDIVO: Grade 3 (n=3), Grade 2 (n=4), and Grade
1 (n=1). In Checkmate 069, adrenal insufficiency occurred in 9%
(8/94) of patients receiving OPDIVO in combination with YERVOY:
Grade 3 (n=3), Grade 2 (n=4), and Grade 1 (n=1). In Checkmate 037,
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 Checkmate 057, Grade 1 or 2 hypothyroidism,
including thyroiditis, occurred in 7% (20/287) and elevated TSH
occurred in 17% of patients receiving OPDIVO. Grade 1 or 2
hyperthyroidism occurred in 1.4% (4/287) of patients. In Checkmate
025, thyroid disease occurred in 43/406 (10.6%) patients receiving
OPDIVO, including one Grade 3 event, and in 12/397 (3.0%) patients
receiving everolimus. Hypothyroidism/thyroiditis occurred in 8.1%
(33/406) of patients receiving OPDIVO: Grade 3 (n=2), Grade 2
(n=17), and Grade 1 (n=14). Hyperthyroidism occurred in 2.5%
(10/406) of patients receiving OPDIVO: Grade 2 (n=5) and Grade 1
(n=5). In Checkmate 069, hypothyroidism occurred in 19% (18/94) of
patients receiving OPDIVO in combination with YERVOY. All were
Grade 1 or 2 in severity except for one patient who experienced
Grade 3 autoimmune thyroiditis. Grade 1 hyperthyroidism occurred in
2.1% (2/94) of patients receiving OPDIVO in combination with
YERVOY. In Checkmate 025, hyperglycemic adverse events occurred in
37/406 (9%) patients. Diabetes mellitus or diabetic ketoacidosis
occurred in 1% (6/406) of patients receiving OPDIVO: Grade 3 (n=3),
Grade 2 (n=2), and Grade 1 (n=1).
In a separate Phase 3 study of YERVOY 3 mg/kg, 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.
Immune-Mediated Nephritis and Renal Dysfunction
Immune-mediated nephritis can occur with OPDIVO treatment.
Monitor patients for elevated serum creatinine prior to and
periodically during treatment. For Grade 2 or 3 increased serum
creatinine, withhold and administer corticosteroids; if worsening
or no improvement occurs, permanently discontinue. Administer
corticosteroids for Grade 4 serum creatinine elevation and
permanently discontinue. In Checkmate 037, 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 Checkmate 057, Grade 2 immune-mediated
renal dysfunction occurred in 0.3% (1/287) of patients receiving
OPDIVO. In Checkmate 025, renal injury occurred in 6.6% (27/406) of
patients receiving OPDIVO and 3.0% (12/397) of patients receiving
everolimus. Immune-mediated nephritis and renal dysfunction
occurred in 3.2% (13/406) of patients receiving OPDIVO: Grade 5
(n=1), Grade 4 (n=1), Grade 3 (n=5), and Grade 2 (n=6). In
Checkmate 069, Grade 2 or higher immune-mediated nephritis or renal
dysfunction occurred in 2.1% (2/94) of patients. One patient died
without resolution of renal dysfunction.
Immune-Mediated Rash
Immune-mediated rash can occur with OPDIVO treatment. Severe
rash (including rare cases of fatal toxic epidermal necrolysis)
occurred in the clinical program of OPDIVO. Monitor patients for
rash. Administer corticosteroids for Grade 3 or 4 rash. Withhold
for Grade 3 and permanently discontinue for Grade 4. In Checkmate
037 (n=268), the incidence of rash was 21%; the incidence of Grade
3 or 4 rash was 0.4%. In Checkmate 057, immune-mediated rash
occurred in 6% (17/287) of patients receiving OPDIVO including four
Grade 3 cases. In Checkmate 025, rash occurred in 28% (112/406) of
patients receiving OPDIVO and 36% (143/397) of patients receiving
everolimus. Immune-mediated rash, defined as a rash treated with
systemic or topical corticosteroids, occurred in 7.4% (30/406) of
patients receiving OPDIVO: Grade 3 (n=4), Grade 2 (n=7), and Grade
1 (n=19). In Checkmate 069, immune-mediated rash occurred in 37%
(35/94) of patients receiving OPDIVO in combination with YERVOY:
Grade 3 (n=6), Grade 2 (n=10), and Grade 1 (n=19).
Immune-Mediated Encephalitis
Immune-mediated encephalitis can occur with OPDIVO treatment.
Withhold OPDIVO in patients with new-onset moderate to severe
neurologic signs or symptoms and evaluate to rule out other causes.
If other etiologies are ruled out, administer corticosteroids and
permanently discontinue OPDIVO for immune-mediated encephalitis.
Across clinical trials of 8490 patients receiving OPDIVO as a
single agent or in combination with YERVOY, <1% of patients were
identified as having encephalitis. In Checkmate 057, fatal limbic
encephalitis occurred in one patient (0.3%) receiving OPDIVO.
Other Immune-Mediated Adverse Reactions
Based on the severity of adverse reaction, permanently
discontinue or withhold treatment, administer high-dose
corticosteroids, and, if appropriate, initiate hormone-replacement
therapy. The following clinically significant immune-mediated
adverse reactions occurred in <2% of single-agent OPDIVO-treated
patients: uveitis, pancreatitis, abducens nerve paresis,
demyelination, polymyalgia rheumatica, autoimmune neuropathy, and
systemic inflammatory response syndrome. Across clinical trials of
OPDIVO administered as a single agent at doses 3 mg/kg and 10
mg/kg, additional clinically significant, immune-mediated adverse
reactions were identified: facial nerve paralysis, motor
dysfunction, vasculitis, and myasthenic syndrome. In Checkmate 069,
the following additional immune-mediated adverse reactions occurred
in 1% of patients treated with OPDIVO in combination with YERVOY:
Guillain-Barré syndrome and hypopituitarism. Across clinical trials
of OPDIVO in combination with YERVOY, the following additional
clinically significant, immune-mediated adverse reactions were
identified: uveitis, sarcoidosis, duodenitis, pancreatitis, and
gastritis.
Infusion Reactions
Severe infusion reactions have been reported in <1% of
patients in clinical trials of OPDIVO as a single agent.
Discontinue OPDIVO in patients with Grade 3 or 4 infusion
reactions. Interrupt or slow the rate of infusion in patients with
Grade 1 or 2. In Checkmate 057, Grade 2 infusion reactions occurred
in 1% (3/287) of patients receiving OPDIVO. In Checkmate 025,
hypersensitivity/infusion-related reactions occurred in 6.2%
(25/406) of patients receiving OPDIVO and 1.0% (4/397) of patients
receiving everolimus. In Checkmate 069, Grade 2 infusion reactions
occurred in 3% (3/94) of patients receiving OPDIVO in combination
with YERVOY. Discontinue OPDIVO in patients with severe or
life-threatening infusion reactions. Interrupt or slow the rate of
infusion in patients with mild or moderate infusion reactions.
Embryofetal Toxicity
Based on their mechanisms of action, OPDIVO and YERVOY 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 an OPDIVO- or YERVOY- containing regimen and for at
least 5 months after the last dose of OPDIVO.
Lactation
It is not known whether OPDIVO or YERVOY 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-containing regimen, advise
women to discontinue breastfeeding during treatment. Advise women
to discontinue nursing during treatment with YERVOY and for 3
months following the final dose.
Serious Adverse Reactions
In Checkmate 037, 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 Checkmate 057,
serious adverse reactions occurred in 47% of patients receiving
OPDIVO. The most frequent serious adverse reactions reported in ≥2%
of patients were pneumonia, pulmonary embolism, dyspnea, pleural
effusion, and respiratory failure. In Checkmate 025, serious
adverse reactions occurred in 47% of patients receiving OPDIVO. The
most frequent serious adverse reactions reported in at least 2% of
patients were acute kidney injury, pleural effusion, pneumonia,
diarrhea, and hypercalcemia. In Checkmate 069, serious adverse
reactions occurred in 62% of patients receiving OPDIVO; the most
frequent serious adverse events with OPDIVO in combination with
YERVOY, as compared to YERVOY alone, were colitis (17% vs 9%),
diarrhea (9% vs 7%), pyrexia (6% vs 7%), and pneumonitis (5% vs
0).
Common Adverse Reactions
In Checkmate 037, the most common adverse reaction (≥20%)
reported with OPDIVO was rash (21%). In Checkmate 057, the most
common adverse reactions (≥20%) reported with OPDIVO were fatigue
(49%), musculoskeletal pain (36%), cough (30%), decreased appetite
(29%), and constipation (23%). In Checkmate 025, the most common
adverse reactions (≥20%) reported in patients receiving OPDIVO vs
everolimus were asthenic conditions (56% vs 57%), cough (34% vs
38%), nausea (28% vs 29%), rash (28% vs 36%), dyspnea (27% vs 31%),
diarrhea (25% vs 32%), constipation (23% vs 18%), decreased
appetite (23% vs 30%), back pain (21% vs 16%), and arthralgia (20%
vs 14%). In Checkmate 069, the most common adverse reactions (≥20%)
reported in patients receiving OPDIVO in combination with YERVOY vs
YERVOY alone were rash (67% vs 57%), pruritus (37% vs 26%),
headache (24% vs 20%), vomiting (23% vs 15%), and colitis (22% vs
11%).
In a separate Phase 3 study of YERVOY 3 mg/kg, 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 U.S. Full Prescribing Information for OPDIVO and
YERVOY including Boxed WARNING for YERVOY regarding
immune-mediated adverse reactions.
About the Bristol-Myers Squibb and Ono
Pharmaceutical Collaboration
In 2011, through a collaboration with Ono Pharmaceutical Co.,
Bristol-Myers Squibb expanded its territorial rights to develop and
commercialize Opdivo globally except in Japan, South Korea and
Taiwan, where Ono had retained all rights to the compound at the
time. On July 23, 2014, Bristol-Myers Squibb and Ono Pharmaceutical
further expanded the companies’ strategic collaboration agreement
to jointly develop and commercialize multiple immunotherapies – as
single agents and combination regimens – for patients with cancer
in Japan, South Korea and Taiwan.
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 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. 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.
References
1. Opdivo Prescribing Information. Opdivo U.S. Product
Information. Last updated: November 23, 2015. Princeton, NJ:
Bristol-Myers Squibb Company.2. Motzer RJ, Escudier B, McDermott
DF, et al. Nivolumab versus everolimus in advanced renal-cell
carcinoma. N Engl J Med. 2015;373(19):1803-1813.3. American Cancer
Society. Kidney cancer (adult) - renal cell carcinoma.
www.cancer.org/acs/groups/cid/documents/webcontent/003107-pdf.pdf.
Updated March 3, 2015. Accessed October 26, 2015.
View source
version on businesswire.com: http://www.businesswire.com/news/home/20151123006375/en/
Bristol-Myers Squibb CompanyMedia:Jaisy Wagner Styles,
609-897-3958Cell:
610-291-5168jaisy.styles@bms.comorInvestors:Ranya Dajani,
609-252-5330ranya.dajani@bms.comorBill Szablewski,
609-252-5894william.szablewski@bms.com
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