Acceptance based on Phase 3 CheckMate -9DW
trial results demonstrating improved survival with Opdivo
(nivolumab) plus Yervoy (ipilimumab) compared to investigator’s
choice of lenvatinib or sorafenib in this patient
population
The U.S. Food and Drug Administration
assigned a target action date of April 21, 2025
Bristol Myers Squibb (NYSE: BMY) today announced that the U.S.
Food and Drug Administration (FDA) has accepted the supplemental
Biologics License Application (sBLA) for Opdivo® (nivolumab) plus
Yervoy® (ipilimumab) as potential first-line treatment for adult
patients with unresectable hepatocellular carcinoma (HCC), based on
results from the Phase 3 CheckMate -9DW trial. The FDA assigned a
Prescription Drug User Fee Act (PDUFA) goal date of April 21,
2025.
“HCC is the most common form of liver cancer and is often
diagnosed when surgery is no longer an option. With the number of
individuals diagnosed with HCC in the United States increasing over
the last decade, new treatment options are urgently needed,” said
Dana Walker, M.D., M.S.C.E., vice president, global program lead,
gastrointestinal and genitourinary cancers, Bristol Myers Squibb.
“Opdivo plus Yervoy showed superior survival benefit compared to
other available treatment options, and we look forward to working
with the FDA to advance our application to potentially bring a new
first-line treatment option to patients.”
The filing was based on the results from the Phase 3 CheckMate
-9DW study in which the combination demonstrated a statistically
significant and clinically meaningful improvement in overall
survival (OS) compared to investigator’s choice of lenvatinib or
sorafenib. The combination of Opdivo plus Yervoy has been an
established second-line treatment for patients with advanced HCC,
and these results support the combination becoming a potential new
treatment option in the first-line setting. The safety profile for
the combination of Opdivo plus Yervoy remained consistent with
previously reported data and was manageable with established
protocols, with no new safety signals identified. Results were
presented at the 2024 American Society of Oncology (ASCO®) Annual
Meeting.
Bristol Myers Squibb thanks the patients and investigators
involved with the Phase 3 CheckMate -9DW clinical trial.
About CheckMate -9DW
CheckMate -9DW is a Phase 3 randomized, open-label trial
evaluating the combination of Opdivo plus Yervoy compared to
investigator’s choice of lenvatinib or sorafenib monotherapy in
patients with unresectable or advanced hepatocellular carcinoma who
have not received prior systemic therapy.
668 patients were randomized to receive Opdivo plus Yervoy
(Opdivo 1mg/kg plus Yervoy 3 mg/kg Q3W for up to four doses,
followed by Opdivo monotherapy 480 mg for a maximum duration of 2
years) infusion, or single agent lenvatinib or sorafenib as oral
capsules in the control arm. The primary endpoint of the trial is
overall survival and key secondary endpoints include objective
response rate and time to symptom deterioration.
About Hepatocellular
Carcinoma
Liver cancer is the third most frequent cause of cancer death
worldwide. Hepatocellular carcinoma (HCC) is the most common type
of primary liver cancer and accounts for 75%-85% of all liver
cancers. HCC is often diagnosed in an advanced stage, where
effective treatment options are limited and are usually associated
with poor outcomes.
Up to 70% of patients experience recurrence within five years,
particularly those still considered to be at high risk after
surgery or ablation. While most cases of HCC are caused by
hepatitis B virus (HBV) or hepatitis C virus (HCV) infections,
metabolic syndrome and nonalcoholic steatohepatitis (NASH) are
rising in prevalence and expected to contribute to increased rates
of HCC.
Bristol Myers Squibb: Creating a Better
Future for People with Cancer
Bristol Myers Squibb is inspired by a single vision —
transforming patients’ lives through science. The goal of the
company’s cancer research is to deliver medicines that offer each
patient a better, healthier life and to make cure a possibility.
Building on a legacy across a broad range of cancers that have
changed survival expectations for many, Bristol Myers Squibb
researchers are exploring new frontiers in personalized medicine
and, through innovative digital platforms, are turning data into
insights that sharpen their focus. Deep understanding of causal
human biology, cutting-edge capabilities and differentiated
research programs uniquely position the company to approach cancer
from every angle.
Cancer can have a relentless grasp on many parts of a patient’s
life, and Bristol Myers Squibb is committed to taking actions to
address all aspects of care, from diagnosis to survivorship. As a
leader in cancer care, Bristol Myers Squibb is working to empower
all people with cancer to have a better future.
About Opdivo
Opdivo is a programmed death-1 (PD-1) immune checkpoint
inhibitor that is designed to uniquely harness the body’s own
immune system to help restore anti-tumor immune response. By
harnessing the body’s own immune system to fight cancer, Opdivo has
become an important treatment option across multiple cancers.
Opdivo’s leading global development program is based on Bristol
Myers Squibb’s scientific expertise in the field of Immuno-Oncology
and includes a broad range of clinical trials across all phases,
including Phase 3, in a variety of tumor types. To date, the Opdivo
clinical development program has treated more than 35,000 patients.
The Opdivo trials have contributed to gaining a deeper
understanding of the potential role of biomarkers in patient care,
particularly regarding how patients may benefit from Opdivo across
the continuum of PD-L1 expression.
In July 2014, Opdivo was the first PD-1 immune checkpoint
inhibitor to receive regulatory approval anywhere in the world.
Opdivo is currently approved in more than 65 countries, including
the United States, the European Union, Japan and China. In October
2015, the Company’s Opdivo and Yervoy combination regimen was the
first Immuno-Oncology combination to receive regulatory approval
for the treatment of metastatic melanoma and is currently approved
in more than 50 countries, including the United States and the
European Union.
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.
INDICATIONS
OPDIVO® (nivolumab), as a single agent, is indicated for the
treatment of adult and pediatric patients 12 years and older with
unresectable or metastatic melanoma.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab),
is indicated for the treatment of adult and pediatric patients 12
years and older with unresectable or metastatic melanoma.
OPDIVO® is indicated for the adjuvant treatment of adult and
pediatric patients 12 years and older with completely resected
Stage IIB, Stage IIC, Stage III, or Stage IV melanoma.
OPDIVO® (nivolumab), in combination with platinum-doublet
chemotherapy, is indicated as neoadjuvant treatment of adult
patients with resectable (tumors ≥4 cm or node positive) non-small
cell lung cancer (NSCLC).
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab),
is indicated for the first-line treatment of adult patients with
metastatic non-small cell lung cancer (NSCLC) whose tumors express
PD-L1 (≥1%) as determined by an FDA-approved test, with no EGFR or
ALK genomic tumor aberrations.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab)
and 2 cycles of platinum-doublet chemotherapy, is indicated for the
first-line treatment of adult patients with metastatic or recurrent
non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic
tumor aberrations.
OPDIVO® (nivolumab) is indicated for the treatment of adult
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.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab),
is indicated for the first-line treatment of adult patients with
unresectable malignant pleural mesothelioma (MPM).
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab),
is indicated for the first-line treatment of adult patients with
intermediate or poor risk advanced renal cell carcinoma (RCC).
OPDIVO® (nivolumab), in combination with cabozantinib, is
indicated for the first-line treatment of adult patients with
advanced renal cell carcinoma (RCC).
OPDIVO® (nivolumab) is indicated for the treatment of adult
patients with advanced renal cell carcinoma (RCC) who have received
prior anti-angiogenic therapy.
OPDIVO® (nivolumab) is indicated for the treatment of adult
patients with classical Hodgkin lymphoma (cHL) that has relapsed or
progressed after autologous hematopoietic stem cell transplantation
(HSCT) and brentuximab vedotin or after 3 or more lines of systemic
therapy that includes autologous HSCT. This indication is approved
under accelerated approval based on overall response rate.
Continued approval for this indication may be contingent upon
verification and description of clinical benefit in confirmatory
trials.
OPDIVO® (nivolumab) is indicated for the treatment of adult
patients with recurrent or metastatic squamous cell carcinoma of
the head and neck (SCCHN) with disease progression on or after
platinum-based therapy.
OPDIVO® (nivolumab) is indicated for the treatment of adult
patients with locally advanced or metastatic urothelial carcinoma
who have disease progression during or following
platinum-containing chemotherapy or have disease progression within
12 months of neoadjuvant or adjuvant treatment with
platinum-containing chemotherapy.
OPDIVO® (nivolumab), as a single agent, is indicated for the
adjuvant treatment of adult patients with urothelial carcinoma (UC)
who are at high risk of recurrence after undergoing radical
resection of UC.
OPDIVO® (nivolumab), in combination with cisplatin and
gemcitabine, is indicated as first-line treatment for adult
patients with unresectable or metastatic urothelial carcinoma.
OPDIVO® (nivolumab), as a single agent, is indicated for the
treatment of adult and pediatric (12 years and older) patients with
microsatellite instability-high (MSI-H) or mismatch repair
deficient (dMMR) metastatic colorectal cancer (CRC) that has
progressed following treatment with a fluoropyrimidine,
oxaliplatin, and irinotecan. This indication is approved under
accelerated approval based on overall response rate and duration of
response. Continued approval for this indication may be contingent
upon verification and description of clinical benefit in
confirmatory trials.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab),
is indicated for the treatment of adults and pediatric patients 12
years and older with microsatellite instability-high (MSI-H) or
mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC)
that has progressed following treatment with a fluoropyrimidine,
oxaliplatin, and irinotecan. This indication is approved under
accelerated approval based on overall response rate and duration of
response. Continued approval for this indication may be contingent
upon verification and description of clinical benefit in
confirmatory trials.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab),
is indicated for the treatment of adult patients with
hepatocellular carcinoma (HCC) who have been previously treated
with sorafenib. This indication is approved under accelerated
approval based on overall response rate and duration of response.
Continued approval for this indication may be contingent upon
verification and description of clinical benefit in the
confirmatory trials.
OPDIVO® (nivolumab) is indicated for the treatment of adult
patients with unresectable advanced, recurrent or metastatic
esophageal squamous cell carcinoma (ESCC) after prior
fluoropyrimidine- and platinum-based chemotherapy.
OPDIVO® (nivolumab) is indicated for the adjuvant treatment of
completely resected esophageal or gastroesophageal junction cancer
with residual pathologic disease in adult patients who have
received neoadjuvant chemoradiotherapy (CRT).
OPDIVO® (nivolumab), in combination with fluoropyrimidine- and
platinum-containing chemotherapy, is indicated for the first-line
treatment of adult patients with unresectable advanced or
metastatic esophageal squamous cell carcinoma (ESCC).
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab),
is indicated for the first-line treatment of adult patients with
unresectable advanced or metastatic esophageal squamous cell
carcinoma (ESCC).
OPDIVO® (nivolumab), in combination with fluoropyrimidine- and
platinum- containing chemotherapy, is indicated for the treatment
of adult patients with advanced or metastatic gastric cancer,
gastroesophageal junction cancer, and esophageal
adenocarcinoma.
IMPORTANT SAFETY
INFORMATION
Severe and Fatal Immune-Mediated Adverse Reactions
Immune-mediated adverse reactions listed herein may not include
all possible severe and fatal immune- mediated adverse
reactions.
Immune-mediated adverse reactions, which may be severe or fatal,
can occur in any organ system or tissue. While immune-mediated
adverse reactions usually manifest during treatment, they can also
occur after discontinuation of OPDIVO or YERVOY. Early
identification and management are essential to ensure safe use of
OPDIVO and YERVOY. Monitor for signs and symptoms that may be
clinical manifestations of underlying immune-mediated adverse
reactions. Evaluate clinical chemistries including liver enzymes,
creatinine, adrenocorticotropic hormone (ACTH) level, and thyroid
function at baseline and periodically during treatment with OPDIVO
and before each dose of YERVOY. In cases of suspected
immune-mediated adverse reactions, initiate appropriate workup to
exclude alternative etiologies, including infection. Institute
medical management promptly, including specialty consultation as
appropriate.
Withhold or permanently discontinue OPDIVO and YERVOY depending
on severity (please see section 2 Dosage and Administration in the
accompanying Full Prescribing Information). In general, if OPDIVO
or YERVOY interruption or discontinuation is required, administer
systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or
equivalent) until improvement to Grade 1 or less. Upon improvement
to Grade 1 or less, initiate corticosteroid taper and continue to
taper over at least 1 month. Consider administration of other
systemic immunosuppressants in patients whose immune-mediated
adverse reactions are not controlled with corticosteroid therapy.
Toxicity management guidelines for adverse reactions that do not
necessarily require systemic steroids (e.g., endocrinopathies and
dermatologic reactions) are discussed below.
Immune-Mediated Pneumonitis
OPDIVO and YERVOY can cause immune-mediated pneumonitis. The
incidence of pneumonitis is higher in patients who have received
prior thoracic radiation. In patients receiving OPDIVO monotherapy,
immune- mediated pneumonitis occurred in 3.1% (61/1994) of
patients, including Grade 4 (<0.1%), Grade 3 (0.9%), and Grade 2
(2.1%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg
every 3 weeks, immune- mediated pneumonitis occurred in 7% (31/456)
of patients, including Grade 4 (0.2%), Grade 3 (2.0%), and Grade 2
(4.4%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg
every 3 weeks, immune- mediated pneumonitis occurred in 3.9%
(26/666) of patients, including Grade 3 (1.4%) and Grade 2 (2.6%).
In NSCLC patients receiving OPDIVO 3 mg/kg every 2 weeks with
YERVOY 1 mg/kg every 6 weeks, immune- mediated pneumonitis occurred
in 9% (50/576) of patients, including Grade 4 (0.5%), Grade 3
(3.5%), and Grade 2 (4.0%). Four patients (0.7%) died due to
pneumonitis.
In Checkmate 205 and 039, pneumonitis, including interstitial
lung disease, occurred in 6.0% (16/266) of patients receiving
OPDIVO. Immune-mediated pneumonitis occurred in 4.9% (13/266) of
patients receiving OPDIVO, including Grade 3 (n=1) and Grade 2
(n=12).
Immune-Mediated Colitis
OPDIVO and YERVOY can cause immune-mediated colitis, which may
be fatal. A common symptom included in the definition of colitis
was diarrhea. Cytomegalovirus (CMV) infection/reactivation has been
reported in patients with corticosteroid-refractory immune-mediated
colitis. In cases of corticosteroid-refractory colitis, consider
repeating infectious workup to exclude alternative etiologies. In
patients receiving OPDIVO monotherapy, immune-mediated colitis
occurred in 2.9% (58/1994) of patients, including Grade 3 (1.7%)
and Grade 2 (1%). In patients receiving OPDIVO 1 mg/kg with YERVOY
3 mg/kg every 3 weeks, immune-mediated colitis occurred in 25%
(115/456) of patients, including Grade 4 (0.4%), Grade 3 (14%) and
Grade 2 (8%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1
mg/kg every 3 weeks, immune-mediated colitis occurred in 9%
(60/666) of patients, including Grade 3 (4.4%) and Grade 2
(3.7%).
Immune-Mediated Hepatitis and
Hepatotoxicity
OPDIVO and YERVOY can cause immune-mediated hepatitis. In
patients receiving OPDIVO monotherapy, immune-mediated hepatitis
occurred in 1.8% (35/1994) of patients, including Grade 4 (0.2%),
Grade 3 (1.3%), and Grade 2 (0.4%). In patients receiving OPDIVO 1
mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated hepatitis
occurred in 15% (70/456) of patients, including Grade 4 (2.4%),
Grade 3 (11%), and Grade 2 (1.8%). In patients receiving OPDIVO 3
mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated hepatitis
occurred in 7% (48/666) of patients, including Grade 4 (1.2%),
Grade 3 (4.9%), and Grade 2 (0.4%).
OPDIVO in combination with cabozantinib can cause hepatic
toxicity with higher frequencies of Grade 3 and 4 ALT and AST
elevations compared to OPDIVO alone. Consider more frequent
monitoring of liver enzymes as compared to when the drugs are
administered as single agents. In patients receiving OPDIVO and
cabozantinib, Grades 3 and 4 increased ALT or AST were seen in 11%
of patients.
Immune-Mediated
Endocrinopathies
OPDIVO and YERVOY can cause primary or secondary adrenal
insufficiency, immune-mediated hypophysitis, immune-mediated
thyroid disorders, and Type 1 diabetes mellitus, which can present
with diabetic ketoacidosis. Withhold OPDIVO and YERVOY depending on
severity (please see section 2 Dosage and Administration in the
accompanying Full Prescribing Information). For Grade 2 or higher
adrenal insufficiency, initiate symptomatic treatment, including
hormone replacement as clinically indicated. Hypophysitis can
present with acute symptoms associated with mass effect such as
headache, photophobia, or visual field defects. Hypophysitis can
cause hypopituitarism; initiate hormone replacement as clinically
indicated. Thyroiditis can present with or without endocrinopathy.
Hypothyroidism can follow hyperthyroidism; initiate hormone
replacement or medical management as clinically indicated. Monitor
patients for hyperglycemia or other signs and symptoms of diabetes;
initiate treatment with insulin as clinically indicated.
In patients receiving OPDIVO monotherapy, adrenal insufficiency
occurred in 1% (20/1994), including Grade 3 (0.4%) and Grade 2
(0.6%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg
every 3 weeks, adrenal insufficiency occurred in 8% (35/456),
including Grade 4 (0.2%), Grade 3 (2.4%), and Grade 2 (4.2%). In
patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3
weeks, adrenal insufficiency occurred in 7% (48/666) of patients,
including Grade 4 (0.3%), Grade 3 (2.5%), and Grade 2 (4.1%). In
patients receiving OPDIVO and cabozantinib, adrenal insufficiency
occurred in 4.7% (15/320) of patients, including Grade 3 (2.2%) and
Grade 2 (1.9%).
In patients receiving OPDIVO monotherapy, hypophysitis occurred
in 0.6% (12/1994) of patients, including Grade 3 (0.2%) and Grade 2
(0.3%).
In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3
weeks, hypophysitis occurred in 9% (42/456), including Grade 3
(2.4%) and Grade 2 (6%). In patients receiving OPDIVO 3 mg/kg with
YERVOY 1 mg/kg every 3 weeks, hypophysitis occurred in 4.4%
(29/666) of patients, including Grade 4 (0.3%), Grade 3 (2.4%), and
Grade 2 (0.9%).
In patients receiving OPDIVO monotherapy, thyroiditis occurred
in 0.6% (12/1994) of patients, including Grade 2 (0.2%). In
patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3
weeks, thyroiditis occurred in 2.7% (22/666) of patients, including
Grade 3 (4.5%) and Grade 2 (2.2%).
In patients receiving OPDIVO monotherapy, hyperthyroidism
occurred in 2.7% (54/1994) of patients, including Grade 3
(<0.1%) and Grade 2 (1.2%). In patients receiving OPDIVO 1 mg/kg
with YERVOY 3 mg/kg every 3 weeks, hyperthyroidism occurred in 9%
(42/456) of patients, including Grade 3 (0.9%) and Grade 2 (4.2%).
In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3
weeks, hyperthyroidism occurred in 12% (80/666) of patients,
including Grade 3 (0.6%) and Grade 2 (4.5%).
In patients receiving OPDIVO monotherapy, hypothyroidism
occurred in 8% (163/1994) of patients, including Grade 3 (0.2%) and
Grade 2 (4.8%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3
mg/kg every 3 weeks, hypothyroidism occurred in 20% (91/456) of
patients, including Grade 3 (0.4%) and Grade 2 (11%). In patients
receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks,
hypothyroidism occurred in 18% (122/666) of patients, including
Grade 3 (0.6%) and Grade 2 (11%).
In patients receiving OPDIVO monotherapy, diabetes occurred in
0.9% (17/1994) of patients, including Grade 3 (0.4%) and Grade 2
(0.3%), and 2 cases of diabetic ketoacidosis. In patients receiving
OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, diabetes occurred
in 2.7% (15/666) of patients, including Grade 4 (0.6%), Grade 3
(0.3%), and Grade 2 (0.9%).
Immune-Mediated Nephritis with Renal
Dysfunction
OPDIVO and YERVOY can cause immune-mediated nephritis. In
patients receiving OPDIVO monotherapy, immune-mediated nephritis
and renal dysfunction occurred in 1.2% (23/1994) of patients,
including Grade 4 (<0.1%), Grade 3 (0.5%), and Grade 2 (0.6%).
In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3
weeks, immune-mediated nephritis with renal dysfunction occurred in
4.1% (27/666) of patients, including Grade 4 (0.6%), Grade 3
(1.1%), and Grade 2 (2.2%).
Immune-Mediated Dermatologic Adverse
Reactions
OPDIVO can cause immune-mediated rash or dermatitis. Exfoliative
dermatitis, including Stevens-Johnson syndrome (SJS), toxic
epidermal necrolysis (TEN), and drug rash with eosinophilia and
systemic symptoms (DRESS) has occurred with PD-1/PD-L1 blocking
antibodies. Topical emollients and/or topical corticosteroids may
be adequate to treat mild to moderate nonexfoliative rashes.
YERVOY can cause immune-mediated rash or dermatitis, including
bullous and exfoliative dermatitis, SJS, TEN, and DRESS. Topical
emollients and/or topical corticosteroids may be adequate to treat
mild to moderate non-bullous/exfoliative rashes.
Withhold or permanently discontinue OPDIVO and YERVOY depending
on severity (please see section 2 Dosage and Administration in the
accompanying Full Prescribing Information).
In patients receiving OPDIVO monotherapy, immune-mediated rash
occurred in 9% (171/1994) of patients, including Grade 3 (1.1%) and
Grade 2 (2.2%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3
mg/kg every 3 weeks, immune-mediated rash occurred in 28% (127/456)
of patients, including Grade 3 (4.8%) and Grade 2 (10%). In
patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3
weeks, immune-mediated rash occurred in 16% (108/666) of patients,
including Grade 3 (3.5%) and Grade 2 (4.2%).
Other Immune-Mediated Adverse
Reactions
The following clinically significant immune-mediated adverse
reactions occurred at an incidence of <1% (unless otherwise
noted) in patients who received OPDIVO monotherapy or OPDIVO in
combination with YERVOY or were reported with the use of other
PD-1/PD-L1 blocking antibodies. Severe or fatal cases have been
reported for some of these adverse reactions: cardiac/vascular:
myocarditis, pericarditis, vasculitis; nervous system: meningitis,
encephalitis, myelitis and demyelination, myasthenic
syndrome/myasthenia gravis (including exacerbation), Guillain-Barré
syndrome, nerve paresis, autoimmune neuropathy; ocular: uveitis,
iritis, and other ocular inflammatory toxicities can occur;
gastrointestinal: pancreatitis to include increases in serum
amylase and lipase levels, gastritis, duodenitis; musculoskeletal
and connective tissue: myositis/polymyositis, rhabdomyolysis, and
associated sequelae including renal failure, arthritis, polymyalgia
rheumatica; endocrine: hypoparathyroidism; other
(hematologic/immune): hemolytic anemia, aplastic anemia,
hemophagocytic lymphohistiocytosis (HLH), systemic inflammatory
response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi
lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid
organ transplant rejection, other transplant (including corneal
graft) rejection.
In addition to the immune-mediated adverse reactions listed
above, across clinical trials of YERVOY monotherapy or in
combination with OPDIVO, the following clinically significant
immune-mediated adverse reactions, some with fatal outcome,
occurred in <1% of patients unless otherwise specified: nervous
system: autoimmune neuropathy (2%), myasthenic syndrome/myasthenia
gravis, motor dysfunction; cardiovascular: angiopathy, temporal
arteritis; ocular: blepharitis, episcleritis, orbital myositis,
scleritis; gastrointestinal: pancreatitis (1.3%); other
(hematologic/immune): conjunctivitis, cytopenias (2.5%),
eosinophilia (2.1%), erythema multiforme, hypersensitivity
vasculitis, neurosensory hypoacusis, psoriasis.
Some ocular IMAR cases can be associated with retinal
detachment. Various grades of visual impairment, including
blindness, can occur. If uveitis occurs in combination with other
immune-mediated adverse reactions, consider a
Vogt-Koyanagi-Harada–like syndrome, which has been observed in
patients receiving OPDIVO and YERVOY, as this may require treatment
with systemic corticosteroids to reduce the risk of permanent
vision loss.
Infusion-Related Reactions
OPDIVO and YERVOY can cause severe infusion-related reactions.
Discontinue OPDIVO and YERVOY in patients with severe (Grade 3) or
life-threatening (Grade 4) infusion-related reactions. Interrupt or
slow the rate of infusion in patients with mild (Grade 1) or
moderate (Grade 2) infusion-related reactions. In patients
receiving OPDIVO monotherapy as a 60-minute infusion,
infusion-related reactions occurred in 6.4% (127/1994) of patients.
In a separate trial in which patients received OPDIVO monotherapy
as a 60-minute infusion or a 30- minute infusion, infusion-related
reactions occurred in 2.2% (8/368) and 2.7% (10/369) of patients,
respectively. Additionally, 0.5% (2/368) and 1.4% (5/369) of
patients, respectively, experienced adverse reactions within 48
hours of infusion that led to dose delay, permanent discontinuation
or withholding of OPDIVO. In melanoma patients receiving OPDIVO 1
mg/kg with YERVOY 3 mg/kg every 3 weeks, infusion-related reactions
occurred in 2.5% (10/407) of patients. In HCC patients receiving
OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, infusion-related
reactions occurred in 8% (4/49) of patients. In RCC patients
receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks,
infusion-related reactions occurred in 5.1% (28/547) of patients.
In MSI- H/dMMR mCRC patients receiving OPDIVO 3 mg/kg with YERVOY 1
mg/kg every 3 weeks, infusion-related reactions occurred in 4.2%
(5/119) of patients. In MPM patients receiving OPDIVO 3 mg/kg every
2 weeks with YERVOY 1 mg/kg every 6 weeks, infusion-related
reactions occurred in 12% (37/300) of patients.
Complications of Allogeneic Hematopoietic Stem Cell
Transplantation
Fatal and other serious complications can occur in patients who
receive allogeneic hematopoietic stem cell transplantation (HSCT)
before or after being treated with OPDIVO or YERVOY.
Transplant-related complications include hyperacute
graft-versus-host-disease (GVHD), acute GVHD, chronic GVHD, hepatic
veno-occlusive disease (VOD) after reduced intensity conditioning,
and steroid-requiring febrile syndrome (without an identified
infectious cause). These complications may occur despite
intervening therapy between OPDIVO or YERVOY and allogeneic
HSCT.
Follow patients closely for evidence of transplant-related
complications and intervene promptly. Consider the benefit versus
risks of treatment with OPDIVO and YERVOY prior to or after an
allogeneic HSCT.
Embryo-Fetal Toxicity
Based on its mechanism of action and findings from animal
studies, OPDIVO and 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 OPDIVO and YERVOY and for at least 5 months after
the last dose.
Increased Mortality in Patients with Multiple Myeloma when
OPDIVO is Added to a Thalidomide Analogue and Dexamethasone
In randomized clinical trials in patients with multiple myeloma,
the addition of OPDIVO to a thalidomide analogue plus dexamethasone
resulted in increased mortality. Treatment of patients with
multiple myeloma with a PD-1 or PD-L1 blocking antibody in
combination with a thalidomide analogue plus dexamethasone is not
recommended outside of controlled clinical trials.
Lactation
There are no data on the presence of OPDIVO or YERVOY in human
milk, the effects on the breastfed child, or the effects on milk
production. Because of the potential for serious adverse reactions
in breastfed children, advise women not to breastfeed during
treatment and for 5 months after the last dose.
Serious Adverse Reactions
In Checkmate 037, serious adverse reactions occurred in 41% of
patients receiving OPDIVO (n=268). 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 066, serious adverse reactions occurred in 36% of
patients receiving OPDIVO (n=206). Grade 3 and 4 adverse reactions
occurred in 41% of patients receiving OPDIVO. The most frequent
Grade 3 and 4 adverse reactions reported in ≥2% of patients
receiving OPDIVO were gamma-glutamyltransferase increase (3.9%) and
diarrhea (3.4%). In Checkmate 067, serious adverse reactions (74%
and 44%), adverse reactions leading to permanent discontinuation
(47% and 18%) or to dosing delays (58% and 36%), and Grade 3 or 4
adverse reactions (72% and 51%) all occurred more frequently in the
OPDIVO plus YERVOY arm (n=313) relative to the OPDIVO arm (n=313).
The most frequent (≥10%) serious adverse reactions in the OPDIVO
plus YERVOY arm and the OPDIVO arm, respectively, were diarrhea
(13% and 2.2%), colitis (10% and 1.9%), and pyrexia (10% and 1.0%).
In Checkmate 238, serious adverse reactions occurred in 18% of
patients receiving OPDIVO (n=452). Grade 3 or 4 adverse reactions
occurred in 25% of OPDIVO-treated patients (n=452). The most
frequent Grade 3 and 4 adverse reactions reported in ≥2% of
OPDIVO-treated patients were diarrhea and increased lipase and
amylase. In Checkmate 816, serious adverse reactions occurred in
30% of patients (n=176) who were treated with OPDIVO in combination
with platinum-doublet chemotherapy. Serious adverse reactions in
>2% included pneumonia and vomiting. No fatal adverse reactions
occurred in patients who received OPDIVO in combination with
platinum-doublet chemotherapy. In Checkmate 227, serious adverse
reactions occurred in 58% of patients (n=576). The most frequent
(≥2%) serious adverse reactions were pneumonia, diarrhea/colitis,
pneumonitis, hepatitis, pulmonary embolism, adrenal insufficiency,
and hypophysitis. Fatal adverse reactions occurred in 1.7% of
patients; these included events of pneumonitis (4 patients),
myocarditis, acute kidney injury, shock, hyperglycemia,
multi-system organ failure, and renal failure. In Checkmate 9LA,
serious adverse reactions occurred in 57% of patients (n=358). The
most frequent (>2%) serious adverse reactions were pneumonia,
diarrhea, febrile neutropenia, anemia, acute kidney injury,
musculoskeletal pain, dyspnea, pneumonitis, and respiratory
failure. Fatal adverse reactions occurred in 7 (2%) patients, and
included hepatic toxicity, acute renal failure, sepsis,
pneumonitis, diarrhea with hypokalemia, and massive hemoptysis in
the setting of thrombocytopenia. In Checkmate 017 and 057, serious
adverse reactions occurred in 46% of patients receiving OPDIVO
(n=418). The most frequent serious adverse reactions reported in
≥2% of patients receiving OPDIVO were pneumonia, pulmonary
embolism, dyspnea, pyrexia, pleural effusion, pneumonitis, and
respiratory failure. In Checkmate 057, fatal adverse reactions
occurred; these included events of infection (7 patients, including
one case of Pneumocystis jirovecii pneumonia), pulmonary embolism
(4 patients), and limbic encephalitis (1 patient). In Checkmate
743, serious adverse reactions occurred in 54% of patients
receiving OPDIVO plus YERVOY. The most frequent serious adverse
reactions reported in ≥2% of patients were pneumonia, pyrexia,
diarrhea, pneumonitis, pleural effusion, dyspnea, acute kidney
injury, infusion-related reaction, musculoskeletal pain, and
pulmonary embolism. Fatal adverse reactions occurred in 4 (1.3%)
patients and included pneumonitis, acute heart failure, sepsis, and
encephalitis. In Checkmate 214, serious adverse reactions occurred
in 59% of patients receiving OPDIVO plus YERVOY (n=547). The most
frequent serious adverse reactions reported in ≥2% of patients were
diarrhea, pyrexia, pneumonia, pneumonitis, hypophysitis, acute
kidney injury, dyspnea, adrenal insufficiency, and colitis. In
Checkmate 9ER, serious adverse reactions occurred in 48% of
patients receiving OPDIVO and cabozantinib (n=320). The most
frequent serious adverse reactions reported in ≥2% of patients were
diarrhea, pneumonia, pneumonitis, pulmonary embolism, urinary tract
infection, and hyponatremia. Fatal intestinal perforations occurred
in 3 (0.9%) patients. In Checkmate 025, serious adverse reactions
occurred in 47% of patients receiving OPDIVO (n=406). The most
frequent serious adverse reactions reported in ≥2% of patients were
acute kidney injury, pleural effusion, pneumonia, diarrhea, and
hypercalcemia. In Checkmate 205 and 039, adverse reactions leading
to discontinuation occurred in 7% and dose delays due to adverse
reactions occurred in 34% of patients (n=266). Serious adverse
reactions occurred in 26% of patients. The most frequent serious
adverse reactions reported in ≥1% of patients were pneumonia,
infusion-related reaction, pyrexia, colitis or diarrhea, pleural
effusion, pneumonitis, and rash. Eleven patients died from causes
other than disease progression: 3 from adverse reactions within 30
days of the last OPDIVO dose, 2 from infection 8 to 9 months after
completing OPDIVO, and 6 from complications of allogeneic HSCT. In
Checkmate 141, serious adverse reactions occurred in 49% of
patients receiving OPDIVO (n=236). The most frequent serious
adverse reactions reported in ≥2% of patients receiving OPDIVO were
pneumonia, dyspnea, respiratory failure, respiratory tract
infection, and sepsis. In Checkmate 275, serious adverse reactions
occurred in 54% of patients receiving OPDIVO (n=270). The most
frequent serious adverse reactions reported in ≥2% of patients
receiving OPDIVO were urinary tract infection, sepsis, diarrhea,
small intestine obstruction, and general physical health
deterioration. In Checkmate 274, serious adverse reactions occurred
in 30% of patients receiving OPDIVO (n=351). The most frequent
serious adverse reaction reported in ≥2% of patients receiving
OPDIVO was urinary tract infection. Fatal adverse reactions
occurred in 1% of patients; these included events of pneumonitis
(0.6%). In Checkmate 901, serious adverse reactions occurred in 48%
of patients receiving OPDIVO in combination with chemotherapy. The
most frequent serious adverse reactions reporting in ≥2% of
patients who received OPDIVO with chemotherapy were urinary tract
infection (4.9%), acute kidney injury (4.3%), anemia (3%),
pulmonary embolism (2.6%), sepsis (2.3%), and platelet count
decreased (2.3%). Fatal adverse reactions occurred in 3.6% of
patients who received OPDIVO in combination with chemotherapy;
these included sepsis (1%). OPDIVO and/or chemotherapy were
discontinued in 30% of patients and were delayed in 67% of patients
for an adverse reaction. In Checkmate 142 in MSI-H/dMMR mCRC
patients receiving OPDIVO with YERVOY (n=119), serious adverse
reactions occurred in 47% of patients. The most frequent serious
adverse reactions reported in ≥2% of patients were
colitis/diarrhea, hepatic events, abdominal pain, acute kidney
injury, pyrexia, and dehydration. In Checkmate 040, serious adverse
reactions occurred in 59% of patients receiving OPDIVO with YERVOY
(n=49). Serious adverse reactions reported in ≥4% of patients were
pyrexia, diarrhea, anemia, increased AST, adrenal insufficiency,
ascites, esophageal varices hemorrhage, hyponatremia, increased
blood bilirubin, and pneumonitis. In Attraction-3, serious adverse
reactions occurred in 38% of patients receiving OPDIVO (n=209).
Serious adverse reactions reported in ≥2% of patients who received
OPDIVO were pneumonia, esophageal fistula, interstitial lung
disease, and pyrexia. The following fatal adverse reactions
occurred in patients who received OPDIVO: interstitial lung disease
or pneumonitis (1.4%), pneumonia (1.0%), septic shock (0.5%),
esophageal fistula (0.5%), gastrointestinal hemorrhage (0.5%),
pulmonary embolism (0.5%), and sudden death (0.5%). In Checkmate
577, serious adverse reactions occurred in 33% of patients
receiving OPDIVO (n=532). A serious adverse reaction reported in
≥2% of patients who received OPDIVO was pneumonitis. A fatal
reaction of myocardial infarction occurred in one patient who
received OPDIVO. In Checkmate 648, serious adverse reactions
occurred in 62% of patients receiving OPDIVO in combination with
chemotherapy (n=310). The most frequent serious adverse reactions
reported in ≥2% of patients who received OPDIVO with chemotherapy
were pneumonia (11%), dysphagia (7%), esophageal stenosis (2.9%),
acute kidney injury (2.9%), and pyrexia (2.3%). Fatal adverse
reactions occurred in 5 (1.6%) patients who received OPDIVO in
combination with chemotherapy; these included pneumonitis,
pneumatosis intestinalis, pneumonia, and acute kidney injury. In
Checkmate 648, serious adverse reactions occurred in 69% of
patients receiving OPDIVO in combination with YERVOY (n=322). The
most frequent serious adverse reactions reported in ≥2% who
received OPDIVO in combination with YERVOY were pneumonia (10%),
pyrexia (4.3%), pneumonitis (4.0%), aspiration pneumonia (3.7%),
dysphagia (3.7%), hepatic function abnormal (2.8%), decreased
appetite (2.8%), adrenal insufficiency (2.5%), and dehydration
(2.5%). Fatal adverse reactions occurred in 5 (1.6%) patients who
received OPDIVO in combination with YERVOY; these included
pneumonitis, interstitial lung disease, pulmonary embolism, and
acute respiratory distress syndrome. In Checkmate 649, serious
adverse reactions occurred in 52% of patients treated with OPDIVO
in combination with chemotherapy (n=782). The most frequent serious
adverse reactions reported in ≥2% of patients treated with OPDIVO
in combination with chemotherapy were vomiting (3.7%), pneumonia
(3.6%), anemia (3.6%), pyrexia (2.8%), diarrhea (2.7%), febrile
neutropenia (2.6%), and pneumonitis (2.4%). Fatal adverse reactions
occurred in 16 (2.0%) patients who were treated with OPDIVO in
combination with chemotherapy; these included pneumonitis (4
patients), febrile neutropenia (2 patients), stroke (2 patients),
gastrointestinal toxicity, intestinal mucositis, septic shock,
pneumonia, infection, gastrointestinal bleeding, mesenteric vessel
thrombosis, and disseminated intravascular coagulation. In
Checkmate 76K, serious adverse reactions occurred in 18% of
patients receiving OPDIVO (n=524). Adverse reactions which resulted
in permanent discontinuation of OPDIVO in >1% of patients
included arthralgia (1.7%), rash (1.7%), and diarrhea (1.1%). A
fatal adverse reaction occurred in 1 (0.2%) patient (heart failure
and acute kidney injury). The most frequent Grade 3-4 lab
abnormalities reported in ≥1% of OPDIVO-treated patients were
increased lipase (2.9%), increased AST (2.2%), increased ALT
(2.1%), lymphopenia (1.1%), and decreased potassium (1.0%).
Common Adverse Reactions
In Checkmate 037, the most common adverse reaction (≥20%)
reported with OPDIVO (n=268) was rash (21%). In Checkmate 066, the
most common adverse reactions (≥20%) reported with OPDIVO (n=206)
vs dacarbazine (n=205) were fatigue (49% vs 39%), musculoskeletal
pain (32% vs 25%), rash (28% vs 12%), and pruritus (23% vs 12%). In
Checkmate 067, the most common (≥20%) adverse reactions in the
OPDIVO plus YERVOY arm (n=313) were fatigue (62%), diarrhea (54%),
rash (53%), nausea (44%), pyrexia (40%), pruritus (39%),
musculoskeletal pain (32%), vomiting (31%), decreased appetite
(29%), cough (27%), headache (26%), dyspnea (24%), upper
respiratory tract infection (23%), arthralgia (21%), and increased
transaminases (25%). In Checkmate 067, the most common (≥20%)
adverse reactions in the OPDIVO arm (n=313) were fatigue (59%),
rash (40%), musculoskeletal pain (42%), diarrhea (36%), nausea
(30%), cough (28%), pruritus (27%), upper respiratory tract
infection (22%), decreased appetite (22%), headache (22%),
constipation (21%), arthralgia (21%), and vomiting (20%). In
Checkmate 238, the most common adverse reactions (≥20%) reported in
OPDIVO-treated patients (n=452) vs ipilimumab-treated patients
(n=453) were fatigue (57% vs 55%), diarrhea (37% vs 55%), rash (35%
vs 47%), musculoskeletal pain (32% vs 27%), pruritus (28% vs 37%),
headache (23% vs 31%), nausea (23% vs 28%), upper respiratory
infection (22% vs 15%), and abdominal pain (21% vs 23%). The most
common immune-mediated adverse reactions were rash (16%),
diarrhea/colitis (6%), and hepatitis (3%). In Checkmate 816, the
most common (>20%) adverse reactions in the OPDIVO plus
chemotherapy arm (n=176) were nausea (38%), constipation (34%),
fatigue (26%), decreased appetite (20%), and rash (20%). In
Checkmate 227, the most common (≥20%) adverse reactions were
fatigue (44%), rash (34%), decreased appetite (31%),
musculoskeletal pain (27%), diarrhea/colitis (26%), dyspnea (26%),
cough (23%), hepatitis (21%), nausea (21%), and pruritus (21%). In
Checkmate 9LA, the most common (>20%) adverse reactions were
fatigue (49%), musculoskeletal pain (39%), nausea (32%), diarrhea
(31%), rash (30%), decreased appetite (28%), constipation (21%),
and pruritus (21%). In Checkmate 017 and 057, the most common
adverse reactions (≥20%) in patients receiving OPDIVO (n=418) were
fatigue, musculoskeletal pain, cough, dyspnea, and decreased
appetite. In Checkmate 743, the most common adverse reactions
(≥20%) in patients receiving OPDIVO plus YERVOY were fatigue (43%),
musculoskeletal pain (38%), rash (34%), diarrhea (32%), dyspnea
(27%), nausea (24%), decreased appetite (24%), cough (23%), and
pruritus (21%). In Checkmate 214, the most common adverse reactions
(≥20%) reported in patients treated with OPDIVO plus YERVOY (n=547)
were fatigue (58%), rash (39%), diarrhea (38%), musculoskeletal
pain (37%), pruritus (33%), nausea (30%), cough (28%), pyrexia
(25%), arthralgia (23%), decreased appetite (21%), dyspnea (20%),
and vomiting (20%). In Checkmate 9ER, the most common adverse
reactions (≥20%) in patients receiving OPDIVO and cabozantinib
(n=320) were diarrhea (64%), fatigue (51%), hepatotoxicity (44%),
palmar-plantar erythrodysaesthesia syndrome (40%), stomatitis
(37%), rash (36%), hypertension (36%), hypothyroidism (34%),
musculoskeletal pain (33%), decreased appetite (28%), nausea (27%),
dysgeusia (24%), abdominal pain (22%), cough (20%) and upper
respiratory tract infection (20%). In Checkmate 025, the most
common adverse reactions (≥20%) reported in patients receiving
OPDIVO (n=406) vs everolimus (n=397) were fatigue (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 205 and 039, the most common
adverse reactions (≥20%) reported in patients receiving OPDIVO
(n=266) were upper respiratory tract infection (44%), fatigue
(39%), cough (36%), diarrhea (33%), pyrexia (29%), musculoskeletal
pain (26%), rash (24%), nausea (20%) and pruritus (20%). In
Checkmate 141, the most common adverse reactions (≥10%) in patients
receiving OPDIVO (n=236) were cough (14%) and dyspnea (14%) at a
higher incidence than investigator’s choice. In Checkmate 275, the
most common adverse reactions (≥20%) reported in patients receiving
OPDIVO (n=270) were fatigue (46%), musculoskeletal pain (30%),
nausea (22%), and decreased appetite (22%). In Checkmate 274, the
most common adverse reactions (≥20%) reported in patients receiving
OPDIVO (n=351) were rash (36%), fatigue (36%), diarrhea (30%),
pruritus (30%), musculoskeletal pain (28%), and urinary tract
infection (22%).In Checkmate 901, the most common adverse reactions
(≥20%) were nausea, fatigue, musculoskeletal pain, constipation,
decreased appetite, rash, vomiting, and peripheral neuropathy. In
Checkmate 142 in MSI- H/dMMR mCRC patients receiving OPDIVO as a
single agent (n=74), the most common adverse reactions (≥20%) were
fatigue (54%), diarrhea (43%), abdominal pain (34%), nausea (34%),
vomiting (28%), musculoskeletal pain (28%), cough (26%), pyrexia
(24%), rash (23%), constipation (20%), and upper respiratory tract
infection (20%). In Checkmate 142 in MSI-H/dMMR mCRC patients
receiving OPDIVO with YERVOY (n=119), the most common adverse
reactions (≥20%) were fatigue (49%), diarrhea (45%), pyrexia (36%),
musculoskeletal pain (36%), abdominal pain (30%), pruritus (28%),
nausea (26%), rash (25%), decreased appetite (20%), and vomiting
(20%). In Checkmate 040, the most common adverse reactions (≥20%)
in patients receiving OPDIVO with YERVOY (n=49), were rash (53%),
pruritus (53%), musculoskeletal pain (41%), diarrhea (39%), cough
(37%), decreased appetite (35%), fatigue (27%), pyrexia (27%),
abdominal pain (22%), headache (22%), nausea (20%), dizziness
(20%), hypothyroidism (20%), and weight decreased (20%). In
Attraction-3, the most common adverse reactions (≥20%) in
OPDIVO-treated patients (n=209) were rash (22%) and decreased
appetite (21%). In Checkmate 577, the most common adverse reactions
(≥20%) in patients receiving OPDIVO (n=532) were fatigue (34%),
diarrhea (29%), nausea (23%), rash (21%), musculoskeletal pain
(21%), and cough (20%). In Checkmate 648, the most common adverse
reactions (≥20%) in patients treated with OPDIVO in combination
with chemotherapy (n=310) were nausea (65%), decreased appetite
(51%), fatigue (47%), constipation (44%), stomatitis (44%),
diarrhea (29%), and vomiting (23%). In Checkmate 648, the most
common adverse reactions reported in ≥20% of patients treated with
OPDIVO in combination with YERVOY were rash (31%), fatigue (28%),
pyrexia (23%), nausea (22%), diarrhea (22%), and constipation
(20%). In Checkmate 649, the most common adverse reactions (≥20%)
in patients treated with OPDIVO in combination with chemotherapy
(n=782) were peripheral neuropathy (53%), nausea (48%), fatigue
(44%), diarrhea (39%), vomiting (31%), decreased appetite (29%),
abdominal pain (27%), constipation (25%), and musculoskeletal pain
(20%). In Checkmate 76K, the most common adverse reactions (≥20%)
reported with OPDIVO (n=524) were fatigue (36%), musculoskeletal
pain (30%), rash (28%), diarrhea (23%) and pruritis (20%).
Please see U.S. Full Prescribing Information for OPDIVO and
YERVOY.
Clinical Trials and Patient
Populations
Checkmate 227–previously untreated metastatic non-small cell
lung cancer, in combination with YERVOY; Checkmate 9LA–previously
untreated recurrent or metastatic non-small cell lung cancer in
combination with YERVOY and 2 cycles of platinum-doublet
chemotherapy by histology; Checkmate 649–previously untreated
advanced or metastatic gastric cancer, gastroesophageal junction
and esophageal adenocarcinoma; Checkmate 577–adjuvant treatment of
esophageal or gastroesophageal junction cancer; Checkmate
238–adjuvant treatment of patients with completely resected Stage
III or Stage IV melanoma; Checkmate 76K–adjuvant treatment of
patients 12 years of age and older with completely resected Stage
IIB or Stage IIC melanoma; Checkmate 274–adjuvant treatment of
urothelial carcinoma; Checkmate 275–previously treated advanced or
metastatic urothelial carcinoma; Checkmate 142–MSI-H or dMMR
metastatic colorectal cancer, as a single agent or in combination
with YERVOY; Checkmate 142–MSI-H or dMMR metastatic colorectal
cancer, as a single agent or in combination with YERVOY;
Attraction-3–esophageal squamous cell carcinoma; Checkmate
648–previously untreated, unresectable advanced recurrent or
metastatic esophageal squamous cell carcinoma; Checkmate
648–previously untreated, unresectable advanced recurrent or
metastatic esophageal squamous cell carcinoma; Checkmate
040–hepatocellular carcinoma, in combination with YERVOY; Checkmate
743–previously untreated unresectable malignant pleural
mesothelioma, in combination with YERVOY; Checkmate 037–previously
treated metastatic melanoma; Checkmate 066–previously untreated
metastatic melanoma; Checkmate 067–previously untreated metastatic
melanoma, as a single agent or in combination with YERVOY;
Checkmate 017–second-line treatment of metastatic squamous
non-small cell lung cancer; Checkmate 057–second-line treatment of
metastatic non-squamous non-small cell lung cancer; Checkmate
816–neoadjuvant non-small cell lung cancer, in combination with
platinum-doublet chemotherapy; Checkmate 901–Adult patients with
unresectable or metastatic urothelial carcinoma; Checkmate
141–recurrent or metastatic squamous cell carcinoma of the head and
neck; Checkmate 025–previously treated renal cell carcinoma;
Checkmate 214–previously untreated renal cell carcinoma, in
combination with YERVOY; Checkmate 9ER–previously untreated renal
cell carcinoma, in combination with cabozantinib; Checkmate
205/039–classical Hodgkin lymphoma.
About the Bristol Myers Squibb and Ono
Pharmaceutical Collaboration
In 2011, through a collaboration agreement 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, Ono and Bristol Myers
Squibb 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 us at BMS.com or
follow us on LinkedIn, Twitter, YouTube, Facebook and
Instagram.
Cautionary Statement Regarding
Forward-Looking Statements
This press release contains “forward-looking statements” within
the meaning of the Private Securities Litigation Reform Act of 1995
regarding, among other things, the research, development and
commercialization of pharmaceutical products. All statements that
are not statements of historical facts are, or may be deemed to be,
forward-looking statements. Such forward-looking statements are
based on current expectations and projections about our future
financial results, goals, plans and objectives and involve inherent
risks, assumptions and uncertainties, including internal or
external factors that could delay, divert or change any of them in
the next several years, that are difficult to predict, may be
beyond our control and could cause our future financial results,
goals, plans and objectives to differ materially from those
expressed in, or implied by, the statements. These risks,
assumptions, uncertainties and other factors include, among others,
that Opdivo (nivolumab) plus Yervoy (ipilimumab) may not receive
regulatory approval for the additional indication described in this
release in the currently anticipated timeline or at all, that any
marketing approvals, if granted, may have significant limitations
on their use, and, if approved, whether such combination treatment
for such additional indication described in this release will be
commercially successful. No forward-looking statement can be
guaranteed. It should also be noted that acceptance of the sBLA
does not change the standards for FDA approval. Forward-looking
statements in this press release should be evaluated together with
the many risks and uncertainties that affect Bristol Myers Squibb’s
business and market, particularly those identified in the
cautionary statement and risk factors discussion in Bristol Myers
Squibb’s Annual Report on Form 10-K for the year ended December 31,
2023, as updated by our subsequent Quarterly Reports on Form 10-Q,
Current Reports on Form 8-K and other filings with the Securities
and Exchange Commission. The forward-looking statements included in
this document are made only as of the date of this document and
except as otherwise required by applicable law, Bristol Myers
Squibb undertakes no obligation to publicly update or revise any
forward-looking statement, whether as a result of new information,
future events, changed circumstances or otherwise.
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