Novel combinations of binimetinib, Opdivo®
(nivolumab) and Yervoy® (ipilimumab) to be studied in
colorectal cancer patients
Array BioPharma (Nasdaq:ARRY) and Bristol-Myers Squibb Company
(NYSE:BMY) today announced the companies have entered into a
clinical research collaboration to investigate the safety,
tolerability and efficacy of Array’s investigational MEK inhibitor,
binimetinib in combination with Bristol-Myers Squibb’s Opdivo
(nivolumab) and Opdivo + Yervoy (ipilimumab) regimen as a potential
treatment for metastatic colorectal cancer in patients with
microsatellite stable tumors.
“Array is pleased to announce this new collaboration with
Bristol-Myers Squibb,” said Ron Squarer, CEO Array BioPharma.
“Based on emerging data, we believe that studying combinations of
targeted therapies, such as binimetinib, with immuno-oncology
agents, such as Opdivo and Yervoy, could provide important
scientific advances for patients fighting cancer.”
“Colorectal cancer remains a challenging tumor where
immunotherapy benefits have been limited to a subset of patients,”
said Fouad Namouni, M.D. head of Oncology Development,
Bristol-Myers Squibb. “We are committed to investigating a wide
range of oncology therapies, and look forward to studying the
combination of Array’s MEK inhibitor and our immunotherapies with
the goal of developing more treatment options for patients.”
The Phase 1/2 study is expected to establish recommended dose
regimens for further study and explore the preliminary anti-tumor
activity of combining binimetinib with Opdivo, as well as
binimetinib in combination with the Opdivo + Yervoy regimen.
Results from this first study, which is anticipated to begin in the
second half of 2017, will be used to determine optimal approaches
to further clinical development of these combinations.
Under the terms of the agreement, Array and Bristol-Myers Squibb
will jointly support the study with Array acting as the
sponsor.
About Colorectal Cancer
Worldwide, colorectal cancer is the third most common type of
cancer in men and the second most common in women, with
approximately 1.4 million new diagnoses in 2012. Of these, nearly
750,000 were diagnosed in men, and 614,000 in women. Globally in
2012, approximately 694,000 deaths were attributed to colorectal
cancer. In the U.S. alone, an estimated 135,430 patients will be
diagnosed with cancer of the colon or rectum in 2017, and
approximately 50,000 are estimated to die of their
disease. There is wide variation in 5-year survival rates
across the globe, with 5-year survival expected to be around 65% in
the developed world and dropping to around 20% in some developing
countries. The incidence of microsatellite stability in colorectal
tumors varies by stage, with nearly 80% of early stage, resectable
tumors and approximately 67% of advanced, metastatic tumors
exhibiting MSS.
About Binimetinib
MEK is a key protein kinase in the MAPK signaling pathway
(RAS-RAF-MEK-ERK). Research has shown this pathway regulates
several key cellular activities including proliferation,
differentiation, survival and angiogenesis. Inappropriate
activation of proteins in this pathway has been shown to occur in
many cancers, such as melanoma, colorectal and thyroid cancers.
Binimetinib is a late-stage small molecule MEK inhibitor which
targets key enzymes in this pathway.
Binimetinib is being studied in clinical trials in advanced
cancer patients, including the Phase 3 COLUMBUS trial in patients
with BRAF-mutant melanoma and the Phase 3 BEACON CRC trial in
patients with BRAF V600E-mutant colorectal cancer.
Bristol-Myers Squibb &
Immuno-Oncology: Advancing Oncology Research
At Bristol-Myers Squibb, patients are at the center of
everything we do. Our vision for the future of cancer care is
focused on researching and developing transformational
Immuno-Oncology (I-O) medicines for hard-to-treat cancers that
could potentially improve outcomes for these patients.
We are leading the scientific understanding of I-O through our
extensive portfolio of investigational compounds and approved
agents. Our differentiated clinical development program is studying
broad patient populations across more than 50 types of cancers with
14 clinical-stage molecules designed to target different immune
system pathways. Our deep expertise and innovative clinical trial
designs position us to advance I-O/I-O, I-O/chemotherapy,
I-O/targeted therapies and I-O/radiation therapies across multiple
tumors and potentially deliver the next wave of therapies with a
sense of urgency. We also continue to pioneer research that will
help facilitate a deeper understanding of the role of immune
biomarkers and how patients’ individual tumor biology can be used
as a guide for treatment decisions throughout their journey.
We understand making the promise of I-O a reality for the many
patients who may benefit from these therapies requires not only
innovation on our part but also close collaboration with leading
experts in the field. Our partnerships with academia, government,
advocacy and biotech companies support our collective goal of
providing new treatment options to advance the standards of
clinical practice.
About Opdivo
Opdivo is a programmed death-1 (PD-1) immune checkpoint
inhibitor that is designed to uniquely harness the body’s own
immune system to help restore anti-tumor immune response. By
harnessing the body’s own immune system to fight
cancer, Opdivo has become an important treatment option
across multiple cancers.
Opdivo’s leading global development program is based on
Bristol-Myers Squibb’s scientific expertise in the field of
Immuno-Oncology and includes a broad range of clinical trials
across all phases, including Phase 3, in a variety of tumor types.
To date, the Opdivo clinical development program has
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 60
countries, including the United States, the European Union and
Japan. In October 2015, the
company’s Opdivo and Yervoy combination regimen was
the first Immuno-Oncology combination to receive regulatory
approval for the treatment of metastatic melanoma and is currently
approved in more than 50 countries, including the United States and
the European Union.
About Yervoy
Yervoy, which is a recombinant, human monoclonal antibody,
blocks the cytotoxic T- lymphocyte-associated antigen-4 (CTLA-4).
CTLA-4 is a negative regulator of T-cell activation. Yervoy binds
to CTLA-4 and blocks the interaction of CTLA-4 with its ligands,
CD80/CD86. Blockade of CTLA-4 has been shown to augment T-cell
activation and proliferation. The mechanism of action of Yervoy
effect in patients with melanoma is indirect, possibly through
T-cell mediated anti-tumor immune responses. On March 25, 2011, the
FDA approved Yervoy 3 mg/kg monotherapy for patients with
unresectable or metastatic melanoma. Yervoy is now approved in more
than 40 countries. There is a broad, ongoing development program in
place for Yervoy spanning multiple tumor types. This includes Phase
3 trials in prostate and lung cancers.
U. S. FDA APPROVED INDICATIONS FOR
OPDIVO ®
OPDIVO® (nivolumab) as a single agent is indicated for the
treatment of patients with BRAF V600 mutation-positive unresectable
or metastatic melanoma. This indication is approved under
accelerated approval based on progression-free survival. Continued
approval for this indication may be contingent upon verification
and description of clinical benefit in the confirmatory trials
OPDIVO® (nivolumab) as a single agent is indicated for the
treatment of patients with BRAF V600 wild-type unresectable or
metastatic melanoma.
OPDIVO® (nivolumab), in combination with
YERVOY® (ipilimumab), is indicated for the treatment of
patients with unresectable or metastatic melanoma. This indication
is approved under accelerated approval based on progression-free
survival. Continued approval for this indication may be contingent
upon verification and description of clinical benefit in the
confirmatory trials.
OPDIVO® (nivolumab) is indicated for the treatment of 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 advanced renal cell carcinoma (RCC) who have received prior
anti-angiogenic therapy.
OPDIVO® (nivolumab) is indicated for the treatment
of adult patients with classical Hodgkin lymphoma (cHL)
that has relapsed or progressed after autologous hematopoietic
stem cell transplantation (HSCT)
and brentuximab vedotin or after 3 or more lines of
systemic therapy that includes autologous HSCT. This indication is
approved under accelerated approval based on overall response rate.
Continued approval for this indication may be contingent upon
verification and description of clinical benefit in confirmatory
trials.
OPDIVO® (nivolumab) is indicated for the treatment of patients
with recurrent or metastatic squamous cell carcinoma of the head
and neck (SCCHN) with disease progression on or after
platinum-based therapy.
OPDIVO® (nivolumab) is indicated for the treatment of patients
with locally advanced or metastatic urothelial carcinoma who have
disease progression during or following platinum-containing
chemotherapy or have disease progression within 12 months of
neoadjuvant or adjuvant treatment with platinum-containing
chemotherapy. 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.
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 with YERVOY, immune-mediated
pneumonitis occurred in 6% (25/407) 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 with YERVOY,
immune-mediated colitis occurred in 26% (107/407) of patients
including three fatal cases.
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. Withhold for Grade 2 and permanently
discontinue for Grade 3 or 4 immune-mediated hepatitis. In
patients receiving OPDIVO monotherapy, immune-mediated hepatitis
occurred in 1.8% (35/1994) of patients. In patients receiving
OPDIVO with YERVOY, immune-mediated hepatitis occurred in 13%
(51/407) of patients.
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 with YERVOY, hypophysitis occurred in 9% (36/407) of
patients. In patients receiving OPDIVO monotherapy,
adrenal insufficiency occurred in 1% (20/1994) of patients. In
patients receiving OPDIVO with YERVOY, adrenal insufficiency
occurred in 5% (21/407) 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 with YERVOY, hypothyroidism or thyroiditis
resulting in hypothyroidism occurred in 22% (89/407) of
patients. Hyperthyroidism occurred in 8% (34/407) of patients
receiving OPDIVO with YERVOY. In patients receiving
OPDIVO monotherapy, diabetes occurred in 0.9% (17/1994) of
patients. In patients receiving OPDIVO with YERVOY,
diabetes occurred in 1.5% (6/407) 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. 6 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 with YERVOY, immune-mediated
nephritis and renal dysfunction occurred in 2.2% (9/407) 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
with YERVOY, immune-mediated rash occurred in 22.6% (92/407)
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 with YERVOY (0.2%) after 1.7 months of
exposure.
Other Immune-Mediated Adverse Reactions
Based on the severity of adverse reaction, permanently
discontinue or withhold treatment, administer high-dose
corticosteroids, and, if appropriate, initiate hormone-replacement
therapy. Across clinical trials of OPDIVO the following clinically
significant immune-mediated adverse reactions occurred in <1.0%
of patients receiving OPDIVO: 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), myositis, myocarditis,
rhabdomyolysis, motor dysfunction, vasculitis,
and myasthenic syndrome.
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, infusion-related reactions occurred in
6.4% (127/1994) of patients. In patients receiving
OPDIVO with YERVOY, infusion-related reactions occurred
in 2.5% (10/407) of patients.
Complications of Allogeneic HSCT after OPDIVO
Complications, including fatal events, occurred in patients who
received allogeneic HSCT after OPDIVO. Outcomes were evaluated in
17 patients from Checkmate 205 and 039, who underwent allogeneic
HSCT after discontinuing OPDIVO (15 with reduced-intensity
conditioning, 2 with myeloablative conditioning).
Thirty-five percent (6/17) of patients died from complications of
allogeneic HSCT after OPDIVO. Five deaths occurred in the setting
of severe or refractory GVHD. Grade 3 or higher acute GVHD was
reported in 29% (5/17) of
patients. Hyperacute GVHD was reported in 20% (n=2)
of patients. A steroid-requiring febrile syndrome, without an
identified infectious cause, was reported in 35% (n=6) of patients.
Two cases of encephalitis were reported: Grade 3 (n=1) lymphocytic
encephalitis without an identified infectious cause, and Grade 3
(n=1) suspected viral encephalitis. Hepatic veno-occlusive
disease (VOD) occurred in one patient, who received
reduced-intensity conditioned allogeneic HSCT and died of GVHD
and multi-organ failure. Other cases of hepatic VOD after
reduced-intensity conditioned allogeneic HSCT have also been
reported in patients with lymphoma who received a PD-1 receptor
blocking antibody before transplantation. Cases of
fatal hyperacute GVHD have also been reported. These
complications may occur despite intervening therapy between PD-1
blockade and allogeneic HSCT.
Follow patients closely for early evidence of transplant-related
complications such as hyperacute GVHD, severe (Grade 3 to
4) acute GVHD, steroid-requiring febrile syndrome, hepatic VOD, and
other immune-mediated adverse reactions, and intervene
promptly.
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.
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 nursing 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 (73%
and 37%), adverse reactions leading to permanent discontinuation
(43% and 14%) or to dosing delays (55% and 28%), and Grade 3 or 4
adverse reactions (72% and 44%) 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 2.6%), colitis (10% and 1.6%), and pyrexia
(10% and 0.6%). 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 at least 2% of
patients receiving OPDIVO were pneumonia, pulmonary embolism,
dyspnea, pyrexia, pleural effusion, pneumonitis, and respiratory
failure. In Checkmate 025, serious adverse reactions occurred
in 47% of patients receiving OPDIVO (n=406). The most frequent
serious adverse reactions reported in ≥2% of patients were acute
kidney injury, pleural effusion, pneumonia, diarrhea, and
hypercalcemia. In Checkmate 205 and 039, adverse reactions
leading to discontinuation occurred in 7% and dose delays due
to adverse reactions occurred in 34% of patients
(n=266). Serious adverse reactions occurred in 26% of
patients. The most frequent serious adverse reactions reported
in ≥1% of patients were pneumonia, infusion-related reaction,
pyrexia, colitis or diarrhea, pleural effusion, pneumonitis,
and rash. Eleven patients died from causes other than
disease progression: 3 from adverse reactions within 30 days
of the last OPDIVO dose, 2 from infection 8 to 9 months after
completing OPDIVO, and 6 from complications of allogeneic
HSCT. In Checkmate 141, serious adverse reactions occurred in 49%
of patients receiving OPDIVO. The most frequent serious adverse
reactions reported in at least 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 at least 2% of
patients receiving OPDIVO were urinary tract infection, sepsis,
diarrhea, small intestine obstruction, and general physical health
deterioration.
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 (59%),
rash (53%), diarrhea (52%), nausea (40%), pyrexia (37%), vomiting
(28%), and dyspnea (20%). The most common (≥20%) adverse reactions
in the OPDIVO (n=313) arm were fatigue (53%), rash (40%), diarrhea
(31%), and nausea (28%). 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 025, the most common adverse
reactions (≥20%) reported in patients receiving OPDIVO (n=406)
vs everolimus (n=397) were asthenic conditions (56% vs
57%), cough (34% vs 38%), nausea (28% vs 29%), rash (28% vs 36%),
dyspnea (27% vs 31%), diarrhea (25% vs 32%), constipation (23% vs
18%), decreased appetite (23% vs 30%), back pain (21% vs 16%), and
arthralgia (20% vs 14%). In Checkmate 205 and 039, the most
common adverse reactions (≥20%) reported in patients receiving
OPDIVO (n=266) were upper respiratory tract infection
(44%), fatigue (39%), cough (36%), diarrhea
(33%), pyrexia (29%), musculoskeletal pain (26%), rash
(24%), nausea (20%) and pruritus (20%). In Checkmate 141, the most
common adverse reactions (≥10%) in patients receiving OPDIVO 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 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.
About Array BioPharma
Array BioPharma Inc. is a biopharmaceutical company focused on
the discovery, development and commercialization of targeted small
molecule drugs to treat patients afflicted with cancer. Seven
Array-owned or partnered drugs are advancing in registration
studies: binimetinib (MEK162), encorafenib (LGX818), selumetinib
(partnered with AstraZeneca), danoprevir (partnered with Roche),
larotrectinib (partnered with Loxo Oncology), tucatinib (partnered
with Cascadian Therapeutics) and ipatasertib (partnered with
Roche).
About the Bristol-Myers Squibb and Ono Pharmaceutical Co.,
Ltd. Collaboration
In 2011, through a collaboration agreement with Ono
Pharmaceutical Co., Ltd (Ono), 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, Bristol-Myers
Squibb and Ono 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.
Array BioPharma Forward-Looking Statement
This press release contains forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of
1995, including statements about the future development plans of
binimetinib and encorafenib, and the timing of the announcement of
further results of clinical trials for binimetinib and encorafenib;
expectations regarding the timing of regulatory filings for
binimetinib and encorafenib and regarding approval of binimetinib
and encorafenib for BRAF-mutant melanoma; expectations that events
will occur that will result in greater value for Array; and the
potential for the results of current and further clinical trials to
support regulatory approval or the marketing success of binimetinib
and encorafenib. These statements involve significant risks and
uncertainties, including those discussed in our most recent annual
report filed on Form 10-K, in our quarterly reports filed on Form
10-Q, and in other reports filed by Array with the Securities and
Exchange Commission. Because these statements reflect our current
expectations concerning future events, our actual results could
differ materially from those anticipated in these forward-looking
statements as a result of many factors. These factors include, but
are not limited to, the determination by the FDA that results from
clinical trials are not sufficient to support registration or
marketing approval of binimetinib and encorafenib; our ability to
effectively and timely conduct clinical trials in light of
increasing costs and difficulties in locating appropriate trial
sites and in enrolling patients who meet the criteria for certain
clinical trials; risks associated with our dependence on
third-party service providers to successfully conduct clinical
trials within and outside the United States; our ability to achieve
and maintain profitability and maintain sufficient cash resources;
and our ability to attract and retain experienced scientists and
management. We are providing this information as of May 30, 2017.
We undertake no duty to update any forward-looking statements to
reflect the occurrence of events or circumstances after the date of
such statements or of anticipated or unanticipated events that
alter any assumptions underlying such statements.
Bristol-Myers Squibb Forward-Looking Statement
This press release contains “forward-looking statements” as that
term is defined in the Private Securities Litigation Reform Act of
1995 regarding the research, development and commercialization of
pharmaceutical products. Such forward-looking statements are
based on current expectations and involve inherent risks and
uncertainties, including factors that could delay, divert or change
any of them, and could cause actual outcomes and results to differ
materially from current expectations. No forward-looking
statement can be guaranteed. Among other risks, there can be
no guarantee that binimetinib in combination with Opdivo or the
Opdivo+Yervoy regimen, will be successfully developed or approved
for any of the indications described in this
release. Forward-looking statements in this press release
should be evaluated together with the many uncertainties that
affect Bristol-Myers Squibb's business, particularly those
identified in the cautionary factors discussion in Bristol-Myers
Squibb's Annual Report on Form 10-K for the year ended December 31,
2016 in our Quarterly Reports on Form 10-Q and our Current Reports
on Form 8-K. Bristol-Myers Squibb undertakes no obligation to
publicly update any forward-looking statement, whether as a result
of new information, future events or otherwise.
View source
version on businesswire.com: http://www.businesswire.com/news/home/20170530005162/en/
Bristol-Myers SquibbMedia:Ken Dominski,
609-252-5251ken.dominski@bms.comorLisa McCormick Lavery,
609-252-7602lisa.mccormicklavery@bms.comorInvestors:Tim
Power, 609-252-7509timothy.power@bms.comorBill Szablewski,
609-252-5894william.szablewski@bms.comorArray BioPharmaTricia Haugeto,
303-386-1193thaugeto@arraybiopharma.com
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