Approval is based on positive results from
the Phase 3 CheckMate -649 trial
Opdivo plus chemotherapy is the first
treatment regimen to demonstrate superior overall survival and
progression-free survival compared to chemotherapy alone in this
patient population
Bristol Myers Squibb Receives European
Commission Approval for Opdivo (nivolumab) + Chemotherapy
for Patients with HER2 Negative, Advanced or Metastatic Gastric,
Gastroesophageal Junction or Esophageal Adenocarcinoma whose Tumors
Express PD-L1 with CPS ≥ 5
Bristol Myers Squibb (NYSE: BMY) today announced that the
European Commission (EC) has approved Opdivo (nivolumab) in
combination with fluoropyrimidine- and platinum-based combination
chemotherapy for the first-line treatment of adult patients with
HER2-negative advanced or metastatic gastric, gastroesophageal
junction (GEJ), or esophageal adenocarcinoma (EAC) whose tumors
express PD-L1 with a combined positive score (CPS) ≥ 5.
The EC’s decision is based on results from the Phase 3 CheckMate
-649 trial, in which first-line treatment with Opdivo plus
leucovorin, 5-fluorouracil and oxaliplatin (FOLFOX) or capecitabine
and oxaliplatin (CapeOX) was compared with chemotherapy alone.
Results from the trial showed a statistically significant and
clinically meaningful improvement in overall survival (OS) and
progression-free survival (PFS) in patients with unresectable
advanced or metastatic gastric cancer (GC), GEJ cancer (GEJC) or
EAC whose tumors express PD-L1 with a CPS ≥ 5 (the primary
endpoints of the study). The statistically significant OS benefit
shown with Opdivo plus chemotherapy was also observed in PD-L1
positive patients with CPS ≥ 1 and in the all-randomized
population. The safety profile observed for Opdivo plus
chemotherapy in the CheckMate -649 trial was consistent with the
known safety profiles of the individual treatments.
“This approval marks a great achievement for many patients with
gastric, gastroesophageal junction and esophageal adenocarcinomas,
who now have a new treatment option that has demonstrated superior
overall survival compared to the long-standing standard of care,”
said Ian M. Waxman, M.D., development lead, gastrointestinal
cancers, Bristol Myers Squibb. “With limited advances for
HER2-negative gastric cancers made in the past ten years, we are
especially pleased to move the field forward and introduce this
Opdivo-based combination for patients in the European Union.”
The EC approval allows for the use of Opdivo in combination with
fluoropyrimidine and platinum-based combination chemotherapy for
the first-line treatment of adult patients with HER2-negative
advanced or metastatic gastric cancer, gastroesophageal junction
(GEJ), or esophageal adenocarcinoma (EAC), whose tumors express
PD-L1 with a combined positive score (CPS) ≥ 5 in the 27 member
states of the European Union, as well as Iceland, Liechtenstein,
and Norway.
CheckMate -649 Efficacy and Safety
Results in Patients with PD-L1 CPS ≥ 5
Results from CheckMate -649 include:
- OS (minimum follow‑up of 19.4 months): Median OS was
14.4 months in patients receiving Opdivo plus chemotherapy (95%
Confidence Interval [CI]: 13.1 to 16.3) compared to 11.1 months
(95% CI: 10.0 to 12.1) in patients receiving chemotherapy alone
(Hazard Ratio [HR] 0.69; 95% CI: 0.60 to 0.81).
- PFS (minimum follow‑up of 19.4 months): Median
PFS was 8.31 months in patients receiving Opdivo plus chemotherapy
(95% CI: 7.03 to 9.26) vs. 6.05 months (95% CI: 5.55 to 6.90) in
patients receiving chemotherapy alone (HR = 0.68; 95% CI: 0.59 to
0.79).
- Safety: The most frequent adverse reactions were
peripheral neuropathy (53%), nausea (48%), fatigue (44%), diarrhea
(39%), vomiting (31%), decreased appetite (29%), abdominal pain
(27%), constipation (25%), musculoskeletal pain (20%), pyrexia
(19%), rash (18%), stomatitis (17%), palmar-plantar
erythrodysaesthesia syndrome (13%), cough (13%), oedema (including
peripheral oedema) (12%), headache (11%), and upper respiratory
tract infection (10%).
About CheckMate -649
CheckMate -649 is a Phase 3 randomized, multi-center, open-label
study evaluating Opdivo plus chemotherapy or the Opdivo plus Yervoy
combination compared to chemotherapy alone in patients with
previously untreated, non-HER2-positive, advanced or metastatic
gastric cancer, gastroesophageal junction cancer or esophageal
adenocarcinoma. Patients in the Opdivo plus chemotherapy arm
received Opdivo 360 mg plus capecitabine and oxaliplatin (CapeOX)
every three weeks or Opdivo 240 mg plus 5-fluorouracil, leucovorin
and oxaliplatin (FOLFOX) every two weeks. Patients in the Opdivo
plus Yervoy arm received Opdivo 1 mg/kg plus Yervoy 3 mg/kg every
three weeks for four cycles followed by Opdivo 240 mg every two
weeks. Patients in the chemotherapy arm received FOLFOX or CapeOX
every two or three weeks, respectively. All patients continued
treatment for two years or until disease progression, unacceptable
toxicity or withdrawal of consent. The primary endpoints of the
trial are overall survival (OS) in PD-L1 positive patients with a
combined positive score (CPS) ≥ 5 treated with Opdivo plus
chemotherapy and PFS, as assessed by Blinded Independent Central
Review (BICR), in CPS ≥ 5 patients treated with Opdivo plus
chemotherapy compared to chemotherapy alone. Secondary endpoints
include OS in CPS ≥ 1 and all randomized patients treated with
Opdivo plus chemotherapy as well as OS and time to symptom
deterioration (TTSD) in patients treated with Opdivo plus Yervoy
compared to chemotherapy alone.
About Gastric Cancer
Gastric cancer, also known as stomach cancer, is the fifth most
common cancer and the fourth leading cause of cancer death
worldwide, with over 1,000,000 new cases and approximately 770,000
deaths in 2020. There are several cancers that can be classified as
gastric cancer, including certain types of cancers that form in the
gastroesophageal junction, the area of the digestive tract where
the esophagus and stomach connect. While GEJ cancer has a lower
prevalence than distal gastric cancer, it continues to rise.
About Esophageal Cancer
Esophageal cancer is the seventh most common cancer and the
sixth leading cause of death from cancer worldwide, with
approximately 600,000 new cases and over 540,000 deaths in 2020.
The two most common types of esophageal cancer are squamous cell
carcinoma and adenocarcinoma, which account for approximately 85%
and 15% of all esophageal cancers, respectively, though esophageal
tumor histology can vary by region with the highest rate of
esophageal adenocarcinoma occurring in North America (65%) and
Europe (~40%).
Bristol Myers Squibb: Creating a Better
Future for People with Cancer
Bristol Myers Squibb is inspired by a single vision —
transforming people’s 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 scientific expertise,
cutting-edge capabilities and discovery platforms enable the
company to look at 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. Because 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 patients with unresectable or metastatic melanoma.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab),
is indicated for the treatment of patients with unresectable or
metastatic melanoma.
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 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 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 patients with advanced
renal cell carcinoma (RCC).
OPDIVO® (nivolumab) is indicated for the treatment of 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 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 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 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 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 adjuvant treatment of
patients with melanoma with involvement of lymph nodes or
metastatic disease who have undergone complete resection.
OPDIVO® (nivolumab) is indicated for the treatment of 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 patients who have received
neoadjuvant chemoradiotherapy (CRT).
OPDIVO® (nivolumab), in combination with fluoropyrimidine- and
platinum-containing chemotherapy, is indicated for the treatment of
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 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 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 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 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.
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 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 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 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 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%).
Please see US Full Prescribing Information for OPDIVO and
YERVOY.
Clinical Trials and Patient Populations
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 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
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 743–previously
untreated unresectable malignant pleural mesothelioma, in
combination with YERVOY; Checkmate 214–previously untreated renal
cell carcinoma, in combination with YERVOY; Checkmate
9ER–previously untreated renal cell carcinoma, in combination with
cabozantinib; Checkmate 025–previously treated renal cell
carcinoma; Checkmate 205/039–classical Hodgkin lymphoma; Checkmate
141–recurrent or metastatic squamous cell carcinoma of the head and
neck; Checkmate 275–previously treated advanced or metastatic
urothelial carcinoma; Checkmate 274–adjuvant treatment of
urothelial carcinoma; Checkmate 142–MSI-H or dMMR metastatic
colorectal cancer, as a single agent or in combination with YERVOY;
Checkmate 040–hepatocellular carcinoma, in combination with YERVOY;
Checkmate 238–adjuvant treatment of melanoma;
Attraction-3–esophageal squamous cell carcinoma; Checkmate
577–adjuvant treatment of esophageal or gastroesophageal junction
cancer; Checkmate 649–previously untreated advanced or metastatic
gastric or gastroesophageal junction or esophageal
adenocarcinoma.
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
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Instagram.
Celgene and Juno Therapeutics are wholly owned subsidiaries of
Bristol-Myers Squibb Company. In certain countries outside the
U.S., due to local laws, Celgene and Juno Therapeutics are referred
to as, Celgene, a Bristol Myers Squibb company and Juno
Therapeutics, a Bristol Myers Squibb company.
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 historical performance and 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 the outcome of pricing and reimbursement
negotiations in individual countries in Europe may delay or limit
the commercial potential of Opdivo for the additional indications
described in this release, any marketing approvals, if granted, may
have significant limitation on their use, that continued approval
of such product candidate for such additional indications described
in this release may be contingent upon verification and description
of clinical benefit in confirmatory trials, and whether such
product candidate for such additional indications described in this
release will be commercially successful. No forward-looking
statement can be guaranteed. 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, 2020, 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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