- Combination of regorafenib and nivolumab vs. regorafenib alone
to be evaluated in patients with micro-satellite stable metastatic
colorectal cancer
- Companies plan indication-seeking trial
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.
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.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20190718005229/en/
Bayer Media Inquiries: Rose Talarico 862-404-5302
rose.talarico@bayer.com
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
Bristol Myers Squibb (NYSE:BMY)
Historical Stock Chart
Von Mär 2024 bis Apr 2024
Bristol Myers Squibb (NYSE:BMY)
Historical Stock Chart
Von Apr 2023 bis Apr 2024