WHIPPANY, N.J.
and PRINCETON, N.J. and OSAKA, Japan, July 18,
2019 /PRNewswire/ -- Bayer, Bristol-Myers Squibb
Company (NYSE: BMY) and Ono Pharmaceutical Co., Ltd. ("Ono")
announced today the three companies have entered into a clinical
collaboration agreement to evaluate the combination of Bayer's
kinase inhibitor Stivarga® (regorafenib) and
Bristol-Myers Squibb's / Ono's anti-PD-1 immune checkpoint
inhibitor, Opdivo® (nivolumab) in patients with
micro-satellite stable metastatic colorectal cancer (MSS mCRC), the
most common form of mCRC.1
Regorafenib as monotherapy has demonstrated an overall survival
benefit versus placebo in the pivotal Phase III CORRECT study and
has shown activity irrespective of micro-satellite status in a
retrospective analysis from this study, though with limited
responses observed.2,3 Despite progress in the treatment
of CRC, including the advance of effective immuno-oncology (I-O)
treatments for certain subsets of CRC, around 95% of mCRC patients
have MSS tumors, for which I-O monotherapy treatment approaches
have shown limited activity.4 Thus, the need for
additional treatment options including combination approaches
remains high.4 Encouraging early data have been seen
with the combination of regorafenib and nivolumab. In a Phase
1b investigator sponsored trial from
Japan called REGONIVO
(NCT03406871, EPOC1603), the combination of regorafenib and
nivolumab has shown promising preliminary efficacy
results.1 The detailed data of the study were presented
at the 2019 American Society of Clinical Oncology (ASCO) Annual
Meeting.
"The data seen in REGONIVO warrant further exploration of the
combination of regorafenib and nivolumab in patients with
colorectal cancer. Regorafenib has proven its efficacy and positive
safety profile as a third-line monotherapy and we are excited to
enter into a clinical collaboration to evaluate this combination
with the hope to deliver an additional therapeutic benefit to
patients," said Scott Z. Fields,
M.D., senior vice president and head of Oncology Development at
Bayer's Pharmaceuticals Division.
"We continue to invest in innovative approaches to maximize the
potential of our pipeline, and interrogate new combinations to help
more patients with cancers typically not responsive to I-O
therapy," said Fouad Namouni, M.D., head of development, oncology,
Bristol-Myers Squibb. "We are looking forward to a strong
collaboration to investigate nivolumab with regorafenib, with the
goal of serving more patients who have cancer."
"We have been actively engaged in the development of nivolumab
including combination therapies with other agents. We are excited
to initiate the clinical collaboration with Bayer and Bristol-Myers
Squibb to investigate this combination therapy as a new treatment
option for patients with colorectal cancer and other types of
cancer," said Kiyoaki Idemitsu, Corporate Officer, Executive
Director, Clinical Development, Ono.
Further terms of the clinical collaboration were not
disclosed.
About Colorectal Cancer5
Colorectal cancer
is a cancer that starts in the colon or the rectum. In the U.S., it
is currently the third most common cancer diagnosed and the second
leading cause of cancer-related deaths when estimates for men and
women are combined. In 2019, an estimated 145,600 Americans will be
diagnosed with colorectal cancer. General estimates predict that 1
in 23 will be diagnosed with the disease in their lifetime.
About Stivarga®
(regorafenib)6
In April
2017, Stivarga was approved for use in patients with
hepatocellular carcinoma who have been previously treated with
Nexavar® (sorafenib). In the
United States, Stivarga is also indicated for the treatment
of patients with metastatic colorectal cancer (CRC) who have been
previously treated with fluoropyrimidine-, oxaliplatin- and
irinotecan-based chemotherapy, an anti-VEGF therapy, and, if RAS
wild-type, an anti-EGFR therapy. It is also indicated for the
treatment of patients with locally advanced, unresectable or
metastatic gastrointestinal stromal tumor (GIST) who have been
previously treated with imatinib mesylate and sunitinib malate.
Regorafenib is a compound developed by Bayer. In 2011, Bayer
entered into an agreement with Onyx, now an Amgen subsidiary, under
which Onyx receives a royalty on all global net sales of
regorafenib in oncology.
Important Safety Information for Stivarga6
WARNING:
HEPATOTOXICITY
•Severe and
sometimes fatal hepatotoxicity has occurred in clinical
trials.
•Monitor hepatic
function prior to and during treatment.
•Interrupt and
then reduce or discontinue STIVARGA for hepatotoxicity as
manifested by elevated liver function tests or hepatocellular
necrosis, depending
upon severity and persistence.
|
Hepatotoxicity: Severe drug-induced liver injury with
fatal outcome occurred in STIVARGA-treated patients across all
clinical trials. In most cases, liver dysfunction occurred within
the first 2 months of therapy and was characterized by a
hepatocellular pattern of injury. In metastatic colorectal cancer
(mCRC), fatal hepatic failure occurred in 1.6% of patients in the
STIVARGA arm and in 0.4% of patients in the placebo arm. In
gastrointestinal stromal tumor (GIST), fatal hepatic failure
occurred in 0.8% of patients in the STIVARGA arm. In hepatocellular
carcinoma (HCC), there was no increase in the incidence of fatal
hepatic failure as compared to placebo.
Liver Function Monitoring: Obtain liver function tests
(ALT, AST, and bilirubin) before initiation of STIVARGA and monitor
at least every 2 weeks during the first 2 months of treatment.
Thereafter, monitor monthly or more frequently as clinically
indicated. Monitor liver function tests weekly in patients
experiencing elevated liver function tests until improvement to
less than 3 times the upper limit of normal (ULN) or baseline
values. Temporarily hold and then reduce or permanently discontinue
STIVARGA, depending on the severity and persistence of
hepatotoxicity as manifested by elevated liver function tests or
hepatocellular necrosis.
Infections: STIVARGA caused an increased risk of
infections. The overall incidence of infection (Grades 1-5) was
higher (32% vs 17%) in 1142 STIVARGA-treated patients as compared
to the control arm in randomized placebo-controlled trials. The
incidence of grade 3 or greater infections in STIVARGA treated
patients was 9%. The most common infections were urinary tract
infections (5.7%), nasopharyngitis (4.0%), mucocutaneous and
systemic fungal infections (3.3%) and pneumonia (2.6%). Fatal
outcomes caused by infection occurred more often in patients
treated with STIVARGA (1.0%) as compared to patients receiving
placebo (0.3%); the most common fatal infections were respiratory
(0.6% vs 0.2%). Withhold STIVARGA for Grade 3 or 4 infections, or
worsening infection of any grade. Resume STIVARGA at the same dose
following resolution of infection.
Hemorrhage: STIVARGA caused an increased incidence of
hemorrhage. The overall incidence (Grades 1-5) was 18.2% in 1142
patients treated with STIVARGA vs 9.5% with placebo in randomized,
placebo-controlled trials. The incidence of grade 3 or greater
hemorrhage in patients treated with STIVARGA was 3.0%. The
incidence of fatal hemorrhagic events was 0.7%, involving the
central nervous system or the respiratory, gastrointestinal, or
genitourinary tracts. Permanently discontinue STIVARGA in patients
with severe or life-threatening hemorrhage and monitor INR levels
more frequently in patients receiving warfarin.
Gastrointestinal Perforation or Fistula: Gastrointestinal
perforation occurred in 0.6% of 4518 patients treated with STIVARGA
across all clinical trials of STIVARGA administered as a single
agent; this included eight fatal events. Gastrointestinal fistula
occurred in 0.8% of patients treated with STIVARGA and in 0.2% of
patients in the placebo arm across randomized, placebo-controlled
trials. Permanently discontinue STIVARGA in patients who develop
gastrointestinal perforation or fistula.
Dermatological Toxicity: In randomized,
placebo-controlled trials, adverse skin reactions occurred in 71.9%
of patients with STIVARGA arm and 25.5% of patients in the placebo
arm including hand-foot skin reaction (HFSR) also known as
palmar-plantar erythrodysesthesia syndrome (PPES) and severe rash,
requiring dose modification. In the randomized, placebo-controlled
trials, the overall incidence of HFSR was higher in 1142
STIVARGA-treated patients (53% vs 8%) than in the placebo-treated
patients. Most cases of HFSR in STIVARGA-treated patients appeared
during the first cycle of treatment. The incidences of Grade 3 HFSR
(16% vs <1%), Grade 3 rash (3% vs <1%), serious adverse
reactions of erythema multiforme (<0.1% vs 0%), and
Stevens-Johnson syndrome (<0.1% vs 0%) were higher in
STIVARGA-treated patients. Across all trials, a higher incidence of
HFSR was observed in Asian patients treated with STIVARGA (all
grades: 72%; Grade 3:18%). Toxic epidermal necrolysis occurred in
0.02% of 4518 STIVARGA-treated patients across all clinical trials
of STIVARGA administered as a single agent. Withhold STIVARGA,
reduce the dose, or permanently discontinue depending on the
severity and persistence of dermatologic toxicity.
Hypertension: Hypertensive crisis occurred in 0.2% in
STIVARGA-treated patients and in none of the patients in placebo
arm across all randomized, placebo-controlled trials. STIVARGA
caused an increased incidence of hypertension (30% vs 8% in mCRC,
59% vs 27% in GIST, and 31% vs 6% in HCC). The onset of
hypertension occurred during the first cycle of treatment in most
patients who developed hypertension (67% in randomized,
placebo-controlled trials). Do not initiate STIVARGA until blood
pressure is adequately controlled. Monitor blood pressure weekly
for the first 6 weeks of treatment and then every cycle, or more
frequently, as clinically indicated. Temporarily or permanently
withhold STIVARGA for severe or uncontrolled hypertension.
Cardiac Ischemia and Infarction: STIVARGA increased the
incidence of myocardial ischemia and infarction (0.9% with STIVARGA
vs 0.2% with placebo) in randomized placebo-controlled trials.
Withhold STIVARGA in patients who develop new or acute cardiac
ischemia or infarction, and resume only after resolution of acute
cardiac ischemic events if the potential benefits outweigh the
risks of further cardiac ischemia.
Reversible Posterior Leukoencephalopathy Syndrome (RPLS):
Reversible posterior leukoencephalopathy syndrome (RPLS), a
syndrome of subcortial vasogenic edema diagnosed by characteristic
finding on MRI occurred in one of 4800 STIVARGA-treated patients
across all clinical trials. Perform an evaluation for RPLS in any
patient presenting with seizures, severe headache, visual
disturbances, confusion, or altered mental function. Discontinue
STIVARGA in patients who develop RPLS.
Wound Healing Complications: Treatment with STIVARGA
should be stopped at least 2 weeks prior to scheduled surgery.
Resuming treatment after surgery should be based on clinical
judgment of adequate wound healing. STIVARGA should be discontinued
in patients with wound dehiscence.
Embryo-Fetal Toxicity: STIVARGA can cause fetal harm when
administered to a pregnant woman. There are no available data on
STIVARGA use in pregnant women. Advise pregnant women of the
potential risk to a fetus. Advise females of reproductive potential
and males with female partners of reproductive potential to use
effective contraception during treatment with STIVARGA and for 2
months after the final dose.
Nursing Mothers: Because of the potential for serious
adverse reactions in breastfed infants from STIVARGA, do not
breastfeed during treatment with STIVARGA and for 2 weeks after the
final dose.
Most Frequently Observed Adverse Drug Reactions in mCRC
(≥30%): The most frequently observed adverse drug
reactions (≥30%) in STIVARGA-treated patients vs placebo-treated
patients in mCRC, respectively, were: asthenia/fatigue (64% vs
46%), pain (59% vs 48%), decreased appetite and food intake (47% vs
28%), HFSR/PPE (45% vs 7%), diarrhea (43% vs 17%), mucositis (33%
vs 5%), weight loss (32% vs 10%), infection (31% vs 17%),
hypertension (30% vs 8%), and dysphonia (30% vs 6%).
Most Frequently Observed Adverse Drug Reactions in GIST
(≥30%): The most frequently observed adverse drug reactions
(≥30%) in STIVARGA-treated patients vs placebo-treated patients in
GIST, respectively, were: HFSR/PPE (67% vs 12%), pain (60% vs 55%),
hypertension (59% vs 27%), asthenia/fatigue (52% vs 39%), diarrhea
(47% vs 9%), mucositis (40% vs 8%), dysphonia (39% vs 9%),
infection (32% vs 5%), decreased appetite and food intake (31% vs
21%), and rash (30% vs 3%).
Most Frequently Observed Adverse Drug Reactions in HCC
(≥30%): The most frequently observed adverse drug
reactions (≥30%) in STIVARGA-treated patients vs placebo-treated
patients in HCC, respectively, were: pain (55% vs 44%), HFSR/PPE
(51% vs 7%), asthenia/fatigue (42% vs 33%), diarrhea (41% vs 15%),
hypertension (31% vs 6%), infection (31% vs 18%), decreased
appetite and food intake (31% vs 15%).
Please see full Prescribing Information,
including Boxed Warning for Stivarga
(regorafenib).
About Oncology at Bayer
Bayer is committed to
delivering science for a better life by advancing a portfolio of
innovative treatments. The oncology franchise at Bayer includes
five marketed products and several other assets in various stages
of clinical development. Together, these products reflect the
company's approach to research, which prioritizes targets and
pathways with the potential to impact the way that cancer is
treated.
About Bayer
Bayer is a global enterprise with core
competencies in the life science fields of health care and
nutrition. Its products and services are designed to benefit people
by supporting efforts to overcome the major challenges presented by
a growing and aging global population. At the same time, the Group
aims to increase its earning power and create value through
innovation and growth. Bayer is committed to the principles of
sustainable development, and the Bayer brand stands for trust,
reliability and quality throughout the world. In fiscal 2018, the
Group employed around 117,000 people and had sales of 39.6
billion euros. Capital expenditures amounted to 2.6 billion
euros, R&D expenses to 5.2 billion euros. For more
information, go to www.bayer.us.
About Opdivo®
(nivolumab)
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 development program 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 enrolled more than 25,000 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.
U.S. FDA-APPROVED INDICATIONS FOR
OPDIVO®7
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) 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) is indicated for the treatment of
patients with metastatic small cell lung cancer (SCLC) with
progression after platinum-based chemotherapy and at least one
other line of therapy. 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) is indicated for the treatment of
patients with advanced renal cell carcinoma (RCC) who have received
prior anti-angiogenic therapy.
OPDIVO® (nivolumab), in combination with
YERVOY® (ipilimumab), is indicated for the treatment of
patients with intermediate or poor risk, previously untreated
advanced renal cell carcinoma (RCC).
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. This indication is approved under
accelerated approval based on tumor 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), 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) 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 tumor response rate and
durability 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.
IMPORTANT SAFETY INFORMATION
WARNING: IMMUNE-MEDIATED ADVERSE REACTIONS
YERVOY can result in severe and fatal immune-mediated adverse
reactions. These immune-mediated reactions may involve any organ
system; however, the most common severe immune-mediated adverse
reactions are enterocolitis, hepatitis, dermatitis (including toxic
epidermal necrolysis), neuropathy, and endocrinopathy. The majority
of these immune-mediated reactions initially manifested during
treatment; however, a minority occurred weeks to months after
discontinuation of YERVOY.
Assess patients for signs and symptoms of enterocolitis,
dermatitis, neuropathy, and endocrinopathy, and evaluate clinical
chemistries including liver function tests (LFTs),
adrenocorticotropic hormone (ACTH) level, and thyroid function
tests, at baseline and before each dose.
Permanently discontinue YERVOY and initiate systemic
high-dose corticosteroid therapy for severe immune-mediated
reactions.
Immune-Mediated Pneumonitis
OPDIVO can cause immune-mediated pneumonitis. Fatal cases have
been reported. Monitor patients for signs with radiographic imaging
and for symptoms of pneumonitis. Administer corticosteroids for
Grade 2 or more severe pneumonitis. Permanently discontinue for
Grade 3 or 4 and withhold until resolution for Grade 2. In
patients receiving OPDIVO monotherapy, fatal cases of
immune-mediated pneumonitis have occurred. Immune-mediated
pneumonitis occurred in 3.1% (61/1994) of patients. In
patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg,
immune-mediated pneumonitis occurred in 6% (25/407) of
patients. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY
1 mg/kg, immune-mediated pneumonitis occurred in 4.4% (24/547) of
patients. In MSI-H/dMMR mCRC patients receiving OPDIVO 3 mg/kg
with YERVOY 1 mg/kg, immune-mediated pneumonitis occurred in 1.7%
(2/119) of patients.
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: Grade 3 (n=1) and Grade 2
(n=12).
Immune-Mediated Colitis
OPDIVO can cause immune-mediated colitis. Monitor patients for
signs and symptoms of colitis. Administer corticosteroids for Grade
2 (of more than 5 days duration), 3, or 4 colitis. Withhold OPDIVO
monotherapy for Grade 2 or 3 and permanently discontinue for Grade
4 or recurrent colitis upon re-initiation of OPDIVO. When
administered with YERVOY, withhold OPDIVO and YERVOY for Grade 2
and permanently discontinue for Grade 3 or 4 or recurrent
colitis. In patients receiving OPDIVO monotherapy,
immune-mediated colitis occurred in 2.9% (58/1994) of
patients. In patients receiving OPDIVO 1 mg/kg with YERVOY 3
mg/kg, immune-mediated colitis occurred in 26% (107/407) of
patients including three fatal cases. In RCC patients
receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated
colitis occurred in 10% (52/547) of patients. In MSI-H/dMMR
mCRC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg,
immune-mediated colitis occurred in 7% (8/119) of patients.
In a separate Phase 3 study of YERVOY 3 mg/kg, severe,
life-threatening, or fatal (diarrhea of ≥7 stools above baseline,
fever, ileus, peritoneal signs; Grade 3-5) immune-mediated
enterocolitis occurred in 34 (7%) patients. Across all
YERVOY-treated patients in that study (n=511), 5 (1%) developed
intestinal perforation, 4 (0.8%) died as a result of complications,
and 26 (5%) were hospitalized for severe enterocolitis.
Immune-Mediated Hepatitis
OPDIVO can cause immune-mediated hepatitis. Monitor patients for
abnormal liver tests prior to and periodically during treatment.
Administer corticosteroids for Grade 2 or greater transaminase
elevations. For patients without HCC, withhold OPDIVO for
Grade 2 and permanently discontinue OPDIVO for Grade 3 or
4. For patients with HCC, withhold OPDIVO and administer
corticosteroids if AST/ALT is within normal limits at baseline and
increases to >3 and up to 5 times the upper limit of normal
(ULN), if AST/ALT is >1 and up to 3 times ULN at baseline and
increases to >5 and up to 10 times the ULN, and if AST/ALT is
>3 and up to 5 times ULN at baseline and increases to >8 and
up to 10 times the ULN. Permanently discontinue OPDIVO and
administer corticosteroids if AST or ALT increases to >10 times
the ULN or total bilirubin increases >3 times the ULN. In
patients receiving OPDIVO monotherapy, immune-mediated hepatitis
occurred in 1.8% (35/1994) of patients. In patients receiving
OPDIVO 1 mg/kg with YERVOY 3 mg/kg, immune-mediated hepatitis
occurred in 13% (51/407) of patients. In RCC patients
receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated
hepatitis occurred in 7% (38/547) of patients. In MSI-H/dMMR
mCRC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg,
immune-mediated hepatitis occurred in 8% (10/119) of
patients.
In Checkmate 040, immune-mediated hepatitis requiring systemic
corticosteroids occurred in 5% (8/154) of patients receiving
OPDIVO.
In a separate Phase 3 study of YERVOY 3 mg/kg, severe,
life-threatening, or fatal hepatotoxicity (AST or ALT elevations
>5x the ULN or total bilirubin elevations >3x the ULN; Grade
3-5) occurred in 8 (2%) patients, with fatal hepatic failure
in 0.2% and hospitalization in 0.4%.
Immune-Mediated Neuropathies
In a separate Phase 3 study of YERVOY 3 mg/kg, 1 case of fatal
Guillain-Barré syndrome and 1 case of severe (Grade 3) peripheral
motor neuropathy were reported.
Immune-Mediated Endocrinopathies
OPDIVO can cause immune-mediated hypophysitis, immune-mediated
adrenal insufficiency, autoimmune thyroid disorders, and Type 1
diabetes mellitus. Monitor patients for signs and symptoms of
hypophysitis, signs and symptoms of adrenal insufficiency, thyroid
function prior to and periodically during treatment, and
hyperglycemia. Administer hormone replacement as clinically
indicated and corticosteroids for Grade 2 or greater hypophysitis.
Withhold for Grade 2 or 3 and permanently discontinue for Grade 4
hypophysitis. Administer corticosteroids for Grade 3 or 4 adrenal
insufficiency. Withhold for Grade 2 and permanently discontinue for
Grade 3 or 4 adrenal insufficiency. Administer hormone-replacement
therapy for hypothyroidism. Initiate medical management for control
of hyperthyroidism. Withhold OPDIVO for Grade 3 and permanently
discontinue for Grade 4 hyperglycemia.
In patients receiving OPDIVO monotherapy, hypophysitis occurred
in 0.6% (12/1994) of patients. In patients receiving OPDIVO 1
mg/kg with YERVOY 3 mg/kg, hypophysitis occurred in 9% (36/407) of
patients. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY
1 mg/kg, hypophysitis occurred in 4.6% (25/547) of
patients. In MSI-H/dMMR mCRC patients receiving OPDIVO 3 mg/kg
with YERVOY 1 mg/kg, immune-mediated hypophysitis occurred in 3.4%
(4/119) of patients. In patients receiving OPDIVO monotherapy,
adrenal insufficiency occurred in 1% (20/1994) of patients. In
patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg, adrenal
insufficiency occurred in 5% (21/407) of patients. In RCC
patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, adrenal
insufficiency occurred in 7% (41/547) of patients. In
MSI-H/dMMR mCRC patients receiving OPDIVO 3 mg/kg with YERVOY 1
mg/kg, adrenal insufficiency occurred in 5.9% (7/119) of
patients. In patients receiving OPDIVO monotherapy,
hypothyroidism or thyroiditis resulting in hypothyroidism occurred
in 9% (171/1994) of patients. Hyperthyroidism occurred in 2.7%
(54/1994) of patients receiving OPDIVO monotherapy. In
patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg,
hypothyroidism or thyroiditis resulting in hypothyroidism occurred
in 22% (89/407) of patients. Hyperthyroidism occurred in 8%
(34/407) of patients receiving this dose of OPDIVO with
YERVOY. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1
mg/kg, hypothyroidism or thyroiditis resulting in hypothyroidism
occurred in 22% (119/547) of patients. Hyperthyroidism occurred in
12% (66/547) of patients receiving this dose of OPDIVO with
YERVOY. In MSI-H/dMMR mCRC patients receiving OPDIVO 3 mg/kg
with YERVOY 1 mg/kg, hypothyroidism or thyroiditis resulting in
hypothyroidism occurred in 15% (18/119) of patients.
Hyperthyroidism occurred in 12% (14/119) of patients. In
patients receiving OPDIVO monotherapy, diabetes occurred in 0.9%
(17/1994) of patients. In patients receiving OPDIVO 1 mg/kg
with YERVOY 3 mg/kg, diabetes occurred in 1.5% (6/407) of
patients. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY
1 mg/kg, diabetes occurred in 2.7% (15/547) of patients.
In a separate Phase 3 study of YERVOY 3 mg/kg, severe to
life-threatening immune-mediated endocrinopathies (requiring
hospitalization, urgent medical intervention, or interfering with
activities of daily living; Grade 3-4) occurred in 9 (1.8%)
patients. All 9 patients had hypopituitarism, and some had
additional concomitant endocrinopathies such as adrenal
insufficiency, hypogonadism, and hypothyroidism. Six of the 9
patients were hospitalized for severe endocrinopathies.
Immune-Mediated Nephritis and Renal Dysfunction
OPDIVO can cause immune-mediated nephritis. Monitor patients for
elevated serum creatinine prior to and periodically during
treatment. Administer corticosteroids for Grades 2-4 increased
serum creatinine. Withhold OPDIVO for Grade 2 or 3 and permanently
discontinue for Grade 4 increased serum creatinine. In
patients receiving OPDIVO monotherapy, immune-mediated nephritis
and renal dysfunction occurred in 1.2% (23/1994) of
patients. In patients receiving OPDIVO 1 mg/kg with YERVOY 3
mg/kg, immune-mediated nephritis and renal dysfunction occurred in
2.2% (9/407) of patients. In RCC patients receiving OPDIVO 3
mg/kg with YERVOY 1 mg/kg, immune-mediated nephritis and renal
dysfunction occurred in 4.6% (25/547) of patients. In
MSI-H/dMMR mCRC patients receiving OPDIVO 3 mg/kg with YERVOY 1
mg/kg, immune-mediated nephritis and renal dysfunction occurred in
1.7% (2/119) of patients.
Immune-Mediated Skin Adverse Reactions and
Dermatitis
OPDIVO can cause immune-mediated rash, including Stevens-Johnson
syndrome (SJS) and toxic epidermal necrolysis (TEN), some cases
with fatal outcome. Administer corticosteroids for Grade 3 or 4
rash. Withhold for Grade 3 and permanently discontinue for Grade 4
rash. For symptoms or signs of SJS or TEN, withhold OPDIVO and
refer the patient for specialized care for assessment and
treatment; if confirmed, permanently discontinue. In patients
receiving OPDIVO monotherapy, immune-mediated rash occurred in 9%
(171/1994) of patients. In patients receiving OPDIVO 1 mg/kg
with YERVOY 3 mg/kg, immune-mediated rash occurred in 22.6%
(92/407) of patients. In RCC patients receiving OPDIVO 3 mg/kg
with YERVOY 1 mg/kg, immune-mediated rash occurred in 16.6%
(91/547) of patients. In MSI-H/dMMR mCRC patients receiving
OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated rash occurred
in 14% (17/119) of patients.
In a separate Phase 3 study of YERVOY 3 mg/kg, severe,
life-threatening, or fatal immune-mediated dermatitis (eg,
Stevens-Johnson syndrome, toxic epidermal necrolysis, or rash
complicated by full thickness dermal ulceration, or necrotic,
bullous, or hemorrhagic manifestations; Grade 3-5) occurred in 13
(2.5%) patients. 1 (0.2%) patient died as a result of toxic
epidermal necrolysis. 1 additional patient required hospitalization
for severe dermatitis.
Immune-Mediated Encephalitis
OPDIVO can cause immune-mediated encephalitis. Evaluation of
patients with neurologic symptoms may include, but not be limited
to, consultation with a neurologist, brain MRI, and lumbar
puncture. Withhold OPDIVO in patients with new-onset moderate to
severe neurologic signs or symptoms and evaluate to rule out other
causes. If other etiologies are ruled out, administer
corticosteroids and permanently discontinue OPDIVO for
immune-mediated encephalitis. In patients receiving OPDIVO
monotherapy, encephalitis occurred in 0.2% (3/1994) of patients.
Fatal limbic encephalitis occurred in one patient after 7.2 months
of exposure despite discontinuation of OPDIVO and administration of
corticosteroids. Encephalitis occurred in one patient
receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg (0.2%) after
1.7 months of exposure. Encephalitis occurred in one RCC
patient receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg (0.2%) after
approximately 4 months of exposure. Encephalitis occurred in
one MSI-H/dMMR mCRC patient (0.8%) receiving OPDIVO 3 mg/kg with
YERVOY 1 mg/kg after 15 days of exposure.
Other Immune-Mediated Adverse Reactions
Based on the severity of the adverse reaction, permanently
discontinue or withhold OPDIVO, administer high-dose
corticosteroids, and, if appropriate, initiate hormone-replacement
therapy. Across clinical trials of OPDIVO monotherapy or in
combination with YERVOY, the following clinically significant
immune-mediated adverse reactions, some with fatal outcome,
occurred in <1.0% of patients receiving OPDIVO: myocarditis,
rhabdomyolysis, myositis, uveitis, iritis, pancreatitis, facial and
abducens nerve paresis, demyelination, polymyalgia rheumatica,
autoimmune neuropathy, Guillain-Barré syndrome, hypopituitarism,
systemic inflammatory response syndrome, gastritis, duodenitis,
sarcoidosis, histiocytic necrotizing lymphadenitis (Kikuchi
lymphadenitis), motor dysfunction, vasculitis, aplastic anemia,
pericarditis, and myasthenic syndrome.
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 may
require treatment with systemic steroids to reduce the risk of
permanent vision loss.
Infusion Reactions
OPDIVO can cause severe infusion reactions, which have been
reported in <1.0% of patients in clinical trials. Discontinue
OPDIVO in patients with Grade 3 or 4 infusion reactions.
Interrupt or slow the rate of infusion in patients with
Grade 1 or 2. In patients receiving OPDIVO monotherapy as a
60-minute infusion, infusion-related reactions occurred
in 6.4% (127/1994) of patients. In a separate study 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 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 RCC patients
receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, 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,
infusion-related reactions occurred in 4.2% (5/119) 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 a PD-1 receptor blocking
antibody. 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 PD-1 blockade and allogeneic
HSCT.
Follow patients closely for evidence of transplant-related
complications and intervene promptly. Consider the benefit versus
risks of treatment with a PD-1 receptor blocking antibody prior to
or after an allogeneic HSCT.
Embryo-Fetal Toxicity
Based on their mechanisms of action, OPDIVO and YERVOY can cause
fetal harm when administered to a pregnant woman. Advise pregnant
women of the potential risk to a fetus. Advise females of
reproductive potential to use effective contraception during
treatment with an OPDIVO- or YERVOY- containing regimen and for at
least 5 months after the last dose of OPDIVO.
Increased Mortality in Patients with Multiple Myeloma when
OPDIVO is Added to a Thalidomide Analogue and
Dexamethasone
In 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
It is not known whether OPDIVO or YERVOY is present in human
milk. Because many drugs, including antibodies, are excreted in
human milk and because of the potential for serious adverse
reactions in nursing infants from an OPDIVO-containing regimen,
advise women to discontinue breastfeeding during treatment. Advise
women to discontinue breastfeeding during treatment with YERVOY and
for 3 months following the final dose.
Serious Adverse Reactions
In Checkmate 037, serious adverse reactions occurred in 41% of
patients receiving OPDIVO (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 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 032, serious adverse reactions occurred
in 45% of patients receiving OPDIVO (n=245). The most frequent
serious adverse reactions reported in at least 2% of patients
receiving OPDIVO were pneumonia, dyspnea, pneumonitis, pleural
effusions, and dehydration. 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 214, serious adverse reactions
occurred in 59% of patients receiving OPDIVO plus YERVOY and in 43%
of patients receiving sunitinib. 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 patients treated with
sunitinib, they were pneumonia, pleural effusion, and
dyspnea. 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 142 in MSI-H/dMMR mCRC patients
receiving OPDIVO with YERVOY, 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 49% of patients (n=154). The most frequent serious
adverse reactions reported in ≥2% of patients were pyrexia,
ascites, back pain, general physical health deterioration,
abdominal pain, and pneumonia. In Checkmate 238, 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. Serious adverse reactions occurred in 18% of
OPDIVO-treated patients.
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 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
032, the most common adverse reactions (≥20%) in patients receiving
OPDIVO (n=245) were fatigue (45%), decreased appetite (27%),
musculoskeletal pain (25%), dyspnea (22%), nausea (22%), diarrhea
(21%), constipation (20%), and cough (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 214, the most common
adverse reactions (≥20%) reported in patients treated with
OPDIVO plus YERVOY (n=547) vs sunitinib (n=535) were fatigue (58%
vs 69%), rash (39% vs 25%), diarrhea (38% vs 58%), musculoskeletal
pain (37% vs 40%), pruritus (33% vs 11%), nausea (30% vs 43%),
cough (28% vs 25%), pyrexia (25% vs 17%), arthralgia (23% vs 16%),
decreased appetite (21% vs 29%), dyspnea (20% vs 21%), and vomiting
(20% vs 28%). 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 and dyspnea 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 142
in MSI-H/dMMR mCRC patients receiving OPDIVO as a single agent, 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, 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 (n=154) were fatigue (38%), musculoskeletal pain
(36%), abdominal pain (34%), pruritus (27%), diarrhea (27%), rash
(26%), cough (23%), and decreased appetite (22%). 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 a separate Phase 3 study of YERVOY 3 mg/kg, the most common
adverse reactions (≥5%) in patients who received YERVOY at
3 mg/kg were fatigue (41%), diarrhea (32%), pruritus (31%),
rash (29%), and colitis (8%).
Please see U.S. Full Prescribing Information
for OPDIVO and YERVOY, including Boxed
WARNING regarding immune-mediated adverse reactions for
YERVOY.
Checkmate 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
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
032–small cell lung cancer; Checkmate 025–previously
treated renal cell carcinoma; Checkmate 214–previously
untreated renal cell carcinoma, in combination with YERVOY;
Checkmate 205/039–classical Hodgkin lymphoma; Checkmate
141–recurrent or metastatic squamous cell carcinoma of the head
and neck; Checkmate 275–urothelial carcinoma; Checkmate
142–MSI-H or dMMR metastatic colorectal cancer, as a single
agent or in combination with YERVOY; Checkmate
040–hepatocellular carcinoma; Checkmate 238–adjuvant
treatment of melanoma.
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 and
Facebook.
About Bristol-Myers Squibb: Advancing Oncology
Research
At Bristol-Myers Squibb, patients are at the center
of everything we do. The focus of our research is to increase
quality, long-term survival for patients and make cure a
possibility. Through a unique multidisciplinary approach powered by
translational science, we harness our deep scientific experience in
oncology and Immuno-Oncology (I-O) research to identify novel
treatments tailored to individual patient needs. Our researchers
are developing a diverse, purposefully built pipeline designed to
target different immune system pathways and address the complex and
specific interactions between the tumor, its microenvironment and
the immune system. We source innovation internally, and in
collaboration with academia, government, advocacy groups and
biotechnology companies, to help make the promise of
transformational medicines, like I-O, a reality for patients.
Contact:
Bayer Media Inquiries:
Rose Talarico
862-404-5302
rose.talarico@bayer.com
Contacts:
Bristol-Myers Squibb Company Media
Inquiries:
Priyanka Shah
609-252-7956
priyanka.shah1@bms.com
Investors:
Tim
Power
609-252-7509
timothy.power@bms.com
ONO PHARMACEUTICAL CO., LTD.:
Corporate
Communications
Public_relations@ono.co.jp
Forward-Looking Statements
This release may contain forward-looking statements based on
current assumptions and forecasts made by Bayer management. Various
known and unknown risks, uncertainties and other factors could lead
to material differences between the actual future results,
financial situation, development or performance of the company and
the estimates given here. These factors include those discussed in
Bayer's public reports which are available on the Bayer website at
www.bayer.com. The company assumes no liability whatsoever to
update these forward-looking statements or to conform them to
future events or developments.
Bristol-Myers Squibb Forward-Looking Statement
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 and the collaboration.
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 expected benefits
of, and opportunities related to, the collaboration may not be
realized by Bristol-Myers Squibb or may take longer to realize than
anticipated, that Opdivo, alone or in combination with Stivarga,
may not receive regulatory approval for the additional indication
described in this release and, if approved, whether such product
candidate for such additional indication 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,
2018, 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.
© 2019 Bayer
BAYER, the Bayer Cross and Stivarga are registered trademarks
of Bayer.
References
- Fukuoka, S; Hara, H;
Takahashi, N et al. Regorafenib in combination with
nivolumab in patients with advanced gastric or colorectal cancer:
an, open-label, dose-finding, and dose-expansion phase 1b trial (REGONIVO, EPOC1603). American Society
of Clinical Oncology 2019; June 2,
2019. Chicago, Illinois.
Abstract 2522.
- Grothey, A; Cutsem, E; Sobrero, A; Siena, S et al.
Regorafenib monotherapy for previously treated metastatic
colorectal cancer (CORRECT): an international, multicentre,
randomised, placebo-controlled, phase 3 trial. Lancet.
2012;381(9863);303-312; January 2013.
https://doi.org/10.1016/S0140-6736(12)61900-X.
- Kochert, K; Beckmann, G; Teufel, M. Exploratory analysis of
baseline microsatellite instability (MSI) status in patients with
metastatic colorectal cancer (mCRC) treated with regorafenib (REG)
or placebo in the phase 3 CORRECT trial. Annals of Oncology.
September 2017.
https://doi.org/10.1093/annonc/mdx393.060.
- Prime Oncology. Immunotherapy Advances for Colorectal Carcinoma
in 2018: Newly Released Data From the Gastrointestinal Cancers
Symposium in San Francisco.
https://www.primeoncology.org/app/uploads/prime_sponsors/27/Gastrointestinal-symposium-CRC-immunotherapy-2018-prime-oncology.pdf.
Accessed July 2019.
- American Cancer Society. Key Statistics for Colorectal Cancer.
https://www.cancer.org/cancer/colon-rectal-cancer/about/key-statistics.html.
Accessed July 2019.
- Stivarga® (Regorafenib) tablets [Prescribing
Information]. Whippany, NJ: Bayer
HealthCare Pharmaceuticals, June
2019.
- OPDIVO (nivolumab) injection, for intravenous use [Prescribing
Information]. Princeton, NJ:
Bristol-Myers Squibb Company, December
2017.
PP-STI-US-0837-1
7/19
View original
content:http://www.prnewswire.com/news-releases/bayer-bristol-myers-squibb-and-ono-pharmaceutical-enter-into-a-clinical-collaboration-agreement-to-investigate-stivarga-regorafenib-and-opdivo-nivolumab-as-combination-therapy-in-patients-with-metastatic-colorectal-cancer-300887326.html
SOURCE Bayer