Applications based on results from CheckMate
-77T, the company’s second positive Phase 3 randomized trial with
an immunotherapy-based combination for the treatment of
non-metastatic non-small cell lung cancer
The perioperative Opdivo-based regimen
demonstrated significant improvement in event-free survival
compared to neoadjuvant chemotherapy and placebo followed by
surgery and adjuvant placebo
The U.S. Food and Drug Administration
assigned a target action date of October 8
Bristol Myers Squibb (NYSE: BMY) today announced two regulatory
acceptances for applications for neoadjuvant Opdivo (nivolumab)
with chemotherapy followed by surgery and adjuvant Opdivo for the
perioperative treatment of resectable stage IIA to IIIB non-small
cell lung cancer (NSCLC). The U.S. Food and Drug Administration
(FDA) accepted the supplemental Biologics Application (sBLA) and
assigned a Prescription Drug User Fee Act (PDUFA) goal date of
October 8, 2024. In late January, the European Medicines Agency
(EMA) validated the type II variation application which confirms
the submission is complete and begins the start of the EMA's
centralized review process.
"Between 30% to 55% of non-small cell lung cancer patients who
undergo surgery will experience disease recurrence. We are working
to expand options that improve outcomes for patients with
resectable disease, as part of our comprehensive approach to the
treatment of multiple types of cancer, including and especially in
earlier stages,” said Abderrahim Oukessou, M.D., vice president,
thoracic cancers global program lead, Bristol Myers Squibb. “With
CheckMate -77T, we have evaluated the potential for neoadjuvant
immunotherapy to induce pathological complete response and the role
of perioperative Opdivo treatment in reducing the likelihood that
the cancer will return and help make extended survival possible for
patients. The acceptance of these applications underscores our
impactful progress in addressing unmet needs across several
non-small cell lung cancer treatment settings and brings us one
step closer to offering a new perioperative Opdivo-based regimen to
patients who may benefit."
The submissions were based on results from the Phase 3 CheckMate
-77T trial, which represents the company’s second positive Phase 3
randomized trial with an immunotherapy-based combination for the
treatment of resectable NSCLC, showing statistically significant
and clinically meaningful improvements in event-free survival
(EFS), the study’s primary endpoint. The study also showed benefits
in key secondary endpoints including pathologic complete response
(pCR) and major pathologic response (MPR). Additionally, the
perioperative regimen had a safety profile consistent with
previously reported studies in NSCLC and no new safety signals were
identified. The EFS, pCR and MPR results from CheckMate -77T were
presented at the European Society of Medical Oncology (ESMO)
Congress 2023. The study remains ongoing to assess another
secondary endpoint of overall survival (OS).
Opdivo and Opdivo-based combinations have shown efficacy
benefits in the neoadjuvant, adjuvant or perioperative settings
across four cancers to date, including lung cancer, bladder cancer,
esophageal/gastroesophageal junction cancer and melanoma.
About CheckMate -77T
CheckMate -77T is a Phase 3 randomized, double-blind,
placebo-controlled, multi-center trial evaluating neoadjuvant
Opdivo with chemotherapy followed by surgery and adjuvant Opdivo
versus neoadjuvant chemotherapy and placebo followed by surgery and
adjuvant placebo in 452 patients with resectable stage IIA to IIIB
non-small cell lung cancer (NSCLC). The primary endpoint of the
trial is event-free survival (EFS). Secondary endpoints include
overall survival (OS), pathologic complete response (pCR) and major
pathologic response (MPR).
About Lung Cancer Lung
cancer is the leading cause of cancer deaths globally. Non-small
cell lung cancer (NSCLC) is one of the most common types of lung
cancer, representing up to 84% of diagnoses. Non-metastatic cases
account for the majority of NSCLC diagnoses (approximately 60%,
with up to half of these being resectable), and the proportion is
expected to grow over time with enhanced screening programs. While
many non-metastatic NSCLC patients are cured by surgery, 30% to 55%
develop recurrence and die of their disease despite resection,
contributing to a need for treatment options administered before
surgery (neoadjuvant) and/or after surgery (adjuvant) to improve
long-term outcomes.
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 platforms 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
September 2015, the Company’s Opdivo and Yervoy combination regimen
was the first Immuno-Oncology 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.
OPDIVO INDICATIONS
OPDIVO® (nivolumab), as a single agent, is indicated for the
treatment of adult and pediatric patients 12 years of age 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 of age 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), 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.
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 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 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 US 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 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
chemotherapy 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 application for Opdivo (nivolumab)
plus chemotherapy does not change the standards for FDA approval
and that the validation by the EMA of the application does not
change the standards for EMA 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, 2022, 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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