Opdivo Study Demonstrates Superior Overall
Survival Compared to Therapy of Investigator’s Choice in Patients
with Recurrent or Metastatic Platinum-Refractory Squamous Cell
Carcinoma of the Head and Neck
Bristol-Myers Squibb Company (NYSE:BMY) today announced that a
randomized Phase 3 study evaluating Opdivo (nivolumab) versus
investigator’s choice in patients with recurrent or metastatic
platinum-refractory squamous cell carcinoma of the head and neck
(SCCHN) was stopped early because an assessment conducted by the
independent Data Monitoring Committee (DMC) concluded that the
study met its primary endpoint, demonstrating superior overall
survival (OS) in patients receiving Opdivo compared to the
control arm. The company looks forward to sharing these data with
health authorities soon.
“With the results of CheckMate -141, Opdivo moves closer to
providing a potential treatment option for patients with head and
neck cancer, a cancer with a high unmet need and limited treatment
options,” said Michael Giordano, M.D., senior vice president, head
of Oncology Development, Bristol-Myers Squibb. “We look
forward to continuing to advance the Opdivo clinical development
program in hard-to-treat cancers, such as head and neck
cancer.”
CheckMate -141 investigators have been informed of the decision
to stop the trial early and Bristol-Myers Squibb is working to
ensure that eligible patients be provided the opportunity to
continue or start treatment with Opdivo as part of the company’s
commitment to providing patient access to Opdivo, and
characterizing long-term survival. The company will complete a full
evaluation of the final CheckMate -141 data, and work with
investigators on the future presentation and publication of the
results.
About CheckMate -141
CheckMate -141 is a Phase 3, open-label, randomized study of
Opdivo versus investigator’s choice of therapy in previously
treated patients with SCCHN who have tumor progression on or within
6 months of platinum therapy in the primary, recurrent, or
metastatic setting. The trial randomized 361 patients 2:1 to
receive either Opdivo 3 mg/kg intravenously every two weeks or
investigator’s choice (cetuximab/methotrexate/docetaxel) until
documented disease progression or unacceptable toxicity. The
primary endpoint is OS. Secondary endpoints include objective
response rate and progression free survival.
About Head & Neck
Cancer
Head and neck cancer is the seventh most common cancer globally,
with an estimated 400,000 to 600,000 new cases per year and 223,000
to 300,000 deaths per year. The five-year survival rate is reported
as less than four percent for metastatic Stage IV disease. SCCHN
accounts for approximately 90 percent of all head and neck cancers
with global incidence expected to increase by 17 percent between
2012 and 2022. Risk factors for SCCHN include tobacco and alcohol
consumption and the increasing role of Human Papilloma Virus (HPV)
infection leading to rapid increase in oropharyngeal SCCHN in
Europe and North America. Quality of life is often impacted for
SCCHN patients as physiological function (breathing, swallowing,
eating, drinking), personal characteristics (appearance, speaking,
voice), sensory function (taste, smell, hearing), and
psychological/social function can be affected.
Bristol-Myers Squibb &
Immuno-Oncology: Advancing Oncology Research
At Bristol-Myers Squibb, we have a vision for the future of
cancer care that is focused on Immuno-Oncology, now considered a
major treatment choice alongside surgery, radiation, chemotherapy
and targeted therapies for certain types of cancer.
We have a comprehensive clinical portfolio of investigational
and approved Immuno-Oncology agents, many of which were discovered
and developed by our scientists. Our ongoing Immuno-Oncology
clinical program is looking at broad patient populations, across
multiple solid tumors and hematologic malignancies, and lines of
therapy and histologies, with the intent of powering our trials for
overall survival and other important measures like durability of
response. We pioneered the research leading to the first regulatory
approval for the combination of two Immuno-Oncology agents, and
continue to study the role of combinations in cancer.
We are also investigating other immune system pathways in the
treatment of cancer including CTLA-4, CD-137, KIR, SLAMF7, PD-1,
GITR, CSF1R, IDO, and LAG-3. These pathways may lead to potential
new treatment options – in combination or monotherapy – to help
patients fight different types of cancers.
Our collaboration with academia, as well as small and large
biotech companies is responsible for researching the potential
Immuno-Oncology and non-Immuno-Oncology combinations, with the goal
of providing new treatment options in clinical practice.
At Bristol-Myers Squibb, we are committed to changing survival
expectations in hard-to-treat cancers and the way patients live
with cancer.
About Opdivo
Cancer cells may exploit “regulatory” pathways, such as
checkpoint pathways, to hide from the immune system and shield the
tumor from immune attack. Opdivo is a PD-1 immune checkpoint
inhibitor that binds to the checkpoint receptor PD-1 expressed on
activated T-cells, and blocks the binding of PD-L1 and PD-L2,
preventing the PD-1 pathway’s suppressive signaling on the immune
system, including the interference with an anti-tumor immune
response.
Opdivo’s broad global development program is based on
Bristol-Myers Squibb’s understanding of the biology behind
Immuno-Oncology. Our company is at the forefront of researching the
potential of Immuno-Oncology to extend survival in hard-to-treat
cancers. This scientific expertise serves as the basis for the
Opdivo development program, which includes a broad range of Phase 3
clinical trials evaluating overall survival as the primary endpoint
across a variety of tumor types. The Opdivo trials have also
contributed toward the clinical and scientific understanding of the
role of biomarkers and how patients may benefit from Opdivo across
the continuum of PD-L1 expression. To date, the Opdivo clinical
development program has enrolled more than 18,000 patients.
Opdivo was the first PD-1 immune checkpoint inhibitor to receive
regulatory approval anywhere in the world in July 2014, and
currently has regulatory approval in 46 countries including the
United States, Japan, and in the European Union.
INDICATIONS
OPDIVO® (nivolumab) as a single agent is indicated for the
treatment of patients with BRAF V600 wild-type unresectable or
metastatic melanoma.
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 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.
IMPORTANT SAFETY
INFORMATION
Immune-Mediated Pneumonitis
Immune-mediated pneumonitis, including fatal cases, occurred
with OPDIVO treatment. Across the clinical trial experience with
solid tumors, fatal immune-mediated pneumonitis occurred with
OPDIVO. Monitor patients for signs with radiographic imaging and
symptoms of pneumonitis. Administer corticosteroids for Grade 2 or
greater pneumonitis. Permanently discontinue for Grade 3 or 4 and
withhold until resolution for Grade 2. In Checkmate 037, 066, and
067, immune-mediated pneumonitis occurred in 1.8% (14/787) of
patients receiving OPDIVO: Grade 3 (n=2) and Grade 2 (n=12). In
Checkmate 057, immune-mediated pneumonitis, including interstitial
lung disease, occurred in 3.4% (10/287) of patients: Grade 3 (n=5),
Grade 2 (n=2), and Grade 1 (n=3). In Checkmate 025, pneumonitis,
including interstitial lung disease, occurred in 5% (21/406) of
patients receiving OPDIVO and 18% (73/397) of patients receiving
everolimus. Immune-mediated pneumonitis occurred in 4.4% (18/406)
of patients receiving OPDIVO: Grade 4 (n=1), Grade 3 (n=4), Grade 2
(n=12), and Grade 1 (n=1).
Immune-Mediated Colitis
Immune-mediated colitis can occur with OPDIVO treatment. Monitor
patients for signs and symptoms of colitis. Administer
corticosteroids for Grade 2 (of more than 5 days duration), 3, or 4
colitis. As a single agent, withhold OPDIVO for Grade 2 or 3 and
permanently discontinue for Grade 4 or recurrent colitis upon
restarting OPDIVO. In Checkmate 037, 066, and 067, diarrhea or
colitis occurred in 31% (242/787) of patients receiving OPDIVO.
Immune-mediated colitis occurred in 4.1% (32/787) of patients:
Grade 3 (n=20), Grade 2 (n=10), and Grade 1 (n=2). In Checkmate
057, diarrhea or colitis occurred in 17% (50/287) of patients
receiving OPDIVO. Immune-mediated colitis occurred in 2.4% (7/287)
of patients: Grade 3 (n=3), Grade 2 (n=2), and Grade 1 (n=2). In
Checkmate 025, diarrhea or colitis occurred in 25% (100/406) of
patients receiving OPDIVO and 32% (126/397) of patients receiving
everolimus. Immune-mediated diarrhea or colitis occurred in 3.2%
(13/406) of patients receiving OPDIVO: Grade 3 (n=5), Grade 2
(n=7), and Grade 1 (n=1).
Immune-Mediated Hepatitis
Immune-mediated hepatitis can occur with OPDIVO treatment.
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
Checkmate 037, 066, and 067, immune-mediated hepatitis occurred in
2.3% (18/787) of patients receiving OPDIVO: Grade 4 (n=3), Grade 3
(n=11), and Grade 2 (n=4). In Checkmate 057, one patient (0.3%)
developed immune-mediated hepatitis. In Checkmate 025, there was an
increased incidence of liver test abnormalities compared to
baseline in AST (33% vs 39%), alkaline phosphatase (32% vs 32%),
ALT (22% vs 31%), and total bilirubin (9% vs 3.5%) in the OPDIVO
and everolimus arms, respectively. Immune-mediated hepatitis
requiring systemic immunosuppression occurred in 1.5% (6/406) of
patients receiving OPDIVO: Grade 3 (n=5) and Grade 2 (n=1).
Immune-Mediated Endocrinopathies
Hypophysitis, adrenal insufficiency, thyroid disorders, and type
1 diabetes mellitus can occur with OPDIVO treatment. Monitor
patients for signs and symptoms of hypophysitis, signs and symptoms
of adrenal insufficiency during and after treatment, thyroid
function prior to and periodically during treatment, and
hyperglycemia. Administer 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. Administer insulin for
type 1 diabetes. Withhold OPDIVO for Grade 3 and permanently
discontinue for Grade 4 hyperglycemia.
In Checkmate 037, 066, and 067, hypophysitis occurred in 0.9%
(7/787) of patients receiving OPDIVO: Grade 3 (n=2), Grade 2 (n=3),
and Grade 1 (n=2). In Checkmate 025, hypophysitis occurred in 0.5%
(2/406) of patients receiving OPDIVO: Grade 3 (n=1) and Grade 1
(n=1). In Checkmate 037, 066, and 067, adrenal insufficiency
occurred in 1% (8/787) of patients receiving OPDIVO: Grade 3 (n=2),
Grade 2 (n=5), and Grade 1 (n=1). In Checkmate 057, 0.3% (1/287) of
OPDIVO-treated patients developed adrenal insufficiency. In
Checkmate 025, adrenal insufficiency occurred in 2.0% (8/406) of
patients receiving OPDIVO: Grade 3 (n=3), Grade 2 (n=4), and Grade
1 (n=1). In Checkmate 037, 066, and 067, hypothyroidism or
thyroiditis occurred in 9% (73/787) of patients receiving OPDIVO:
Grade 3 (n=1), Grade 2 (n=37), Grade 1 (n=35). Hyperthyroidism
occurred in 4.4% (35/787) of patients receiving OPDIVO: Grade 3
(n=1), Grade 2 (n=12), and Grade 1 (n=22). In Checkmate 057, Grade
1 or 2 hypothyroidism, including thyroiditis, occurred in 7%
(20/287) and elevated thyroid stimulating hormone occurred in 17%
of patients receiving OPDIVO. Grade 1 or 2 hyperthyroidism occurred
in 1.4% (4/287) of patients. In Checkmate 025, thyroid disease
occurred in 11% (43/406) of patients receiving OPDIVO, including
one Grade 3 event, and in 3.0% (12/397) of patients receiving
everolimus. Hypothyroidism/thyroiditis occurred in 8% (33/406) of
patients receiving OPDIVO: Grade 3 (n=2), Grade 2 (n=17), and Grade
1 (n=14). Hyperthyroidism occurred in 2.5% (10/406) of patients
receiving OPDIVO: Grade 2 (n=5) and Grade 1 (n=5). In Checkmate
037, 066, and 067, diabetes mellitus or diabetic ketoacidosis
occurred in 0.8% (6/787) of patients receiving OPDIVO: Grade 3
(n=2), Grade 2 (n=3), and Grade 1 (n=1). In Checkmate 025,
hyperglycemic adverse events occurred in 9% (37/406) patients.
Diabetes mellitus or diabetic ketoacidosis occurred in 1.5% (6/406)
of patients receiving OPDIVO: Grade 3 (n=3), Grade 2 (n=2), and
Grade 1 (n=1).
Immune-Mediated Nephritis and Renal Dysfunction
Immune-mediated nephritis can occur with OPDIVO treatment.
Monitor patients for elevated serum creatinine prior to and
periodically during treatment. For Grade 2 or 3 increased serum
creatinine, withhold and administer corticosteroids; if worsening
or no improvement occurs, permanently discontinue. Administer
corticosteroids for Grade 4 serum creatinine elevation and
permanently discontinue. In Checkmate 037, 066, and 067, nephritis
and renal dysfunction of any grade occurred in 5% (40/787) of
patients receiving OPDIVO. Immune-mediated nephritis and renal
dysfunction occurred in 0.8% (6/787) of patients: Grade 3 (n=4) and
Grade 2 (n=2). In Checkmate 057, Grade 2 immune-mediated renal
dysfunction occurred in 0.3% (1/287) of patients receiving OPDIVO.
In Checkmate 025, renal injury occurred in 7% (27/406) of patients
receiving OPDIVO and 3.0% (12/397) of patients receiving
everolimus. Immune-mediated nephritis and renal dysfunction
occurred in 3.2% (13/406) of patients receiving OPDIVO: Grade 5
(n=1), Grade 4 (n=1), Grade 3 (n=5), and Grade 2 (n=6).
Immune-Mediated Rash
Immune-mediated rash can occur with OPDIVO treatment. Severe
rash (including rare cases of fatal toxic epidermal necrolysis)
occurred in the clinical program of OPDIVO. Monitor patients for
rash. Administer corticosteroids for Grade 3 or 4 rash. Withhold
for Grade 3 and permanently discontinue for Grade 4. In Checkmate
037, 066, and 067, immune-mediated rash occurred in 9% (72/787) of
patients receiving OPDIVO: Grade 3 (n=7), Grade 2 (n=15), and Grade
1 (n=50). In Checkmate 057, immune-mediated rash occurred in 6%
(17/287) of patients receiving OPDIVO including four Grade 3 cases.
In Checkmate 025, rash occurred in 28% (112/406) of patients
receiving OPDIVO and 36% (143/397) of patients receiving
everolimus. Immune-mediated rash, defined as a rash treated with
systemic or topical corticosteroids, occurred in 7% (30/406) of
patients receiving OPDIVO: Grade 3 (n=4), Grade 2 (n=7), and Grade
1 (n=19).
Immune-Mediated Encephalitis
Immune-mediated encephalitis can occur with OPDIVO treatment.
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
Checkmate 057, fatal limbic encephalitis occurred in one patient
(0.3%) receiving OPDIVO.
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. In < 1.0% of patients receiving OPDIVO, the following
clinically significant, immune-mediated adverse reactions occurred:
uveitis, pancreatitis, facial and abducens nerve paresis,
demyelination, polymyalgia rheumatica, autoimmune neuropathy,
Guillain-Barré syndrome, hypopituitarism, systemic inflammatory
response syndrome, gastritis, duodenitis, and sarcoidosis. Across
clinical trials of OPDIVO as a single agent administered at doses
of 3 mg/kg and 10 mg/kg, additional clinically significant,
immune-mediated adverse reactions were identified: motor
dysfunction, vasculitis, and myasthenic syndrome.
Infusion Reactions
Severe infusion reactions have been reported in <1.0% of
patients in clinical trials of OPDIVO. 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 Checkmate
037, 066, and 067, Grade 2 infusion related reactions occurred in
2.7% (21/787) of patients receiving OPDIVO: Grade 3 (n=2), Grade 2
(n=8), and Grade 1 (n=11). In Checkmate 057, Grade 2 infusion
reactions requiring corticosteroids occurred in 1.0% (3/287) of
patients receiving OPDIVO. In Checkmate 025,
hypersensitivity/infusion-related reactions occurred in 6% (25/406)
of patients receiving OPDIVO and 1.0% (4/397) of patients receiving
everolimus.
Embryo-fetal Toxicity
Based on its mechanism of action, OPDIVO 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-
containing regimen and for at least 5 months after the last dose of
OPDIVO.
Lactation
It is not known whether OPDIVO 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.
Serious Adverse Reactions
In Checkmate 067, serious adverse reactions (37%), adverse
reactions leading to permanent discontinuation (14%) or to dosing
delays (28%), and Grade 3 or 4 adverse reactions (72%) occurred in
the OPDIVO arm. The most frequent (≥10%) serious adverse reactions
in the OPDIVO arm were diarrhea (2.6%), colitis (1.6%), and pyrexia
(0.6%). In Checkmate 037, serious adverse reactions occurred in 41%
of patients receiving OPDIVO. 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. 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 057, serious adverse reactions occurred in 47% of
patients receiving OPDIVO. The most frequent serious adverse
reactions reported in ≥2% of patients were pneumonia, pulmonary
embolism, dyspnea, pleural effusion, and respiratory failure. In
Checkmate 025, serious adverse reactions occurred in 47% of
patients receiving OPDIVO. The most frequent serious adverse
reactions reported in ≥2% of patients were acute kidney injury,
pleural effusion, pneumonia, diarrhea, and hypercalcemia.
Common Adverse Reactions
In Checkmate 067, the most common (≥20%) adverse reactions in
the OPDIVO arm were fatigue (53%), rash (40%), diarrhea (31%), and
nausea (28%). In Checkmate 037, the most common adverse reaction
(≥20%) reported with OPDIVO was rash (21%). In Checkmate 066, the
most common adverse reactions (≥20%) reported with OPDIVO vs
dacarbazine were fatigue (49% vs 39%), musculoskeletal pain (32% vs
25%), rash (28% vs 12%), and pruritus (23% vs 12%). In Checkmate
057, the most common adverse reactions (≥20%) reported with OPDIVO
were fatigue (49%), musculoskeletal pain (36%), cough (30%),
decreased appetite (29%), and constipation (23%). In Checkmate 025,
the most common adverse reactions (≥20%) reported in patients
receiving OPDIVO vs everolimus 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%).
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, Bristol-Myers
Squibb and Ono Pharmaceutical 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.
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 www.bms.com, or
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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 Opdivo will receive regulatory approval for an additional
indication in SCCHN. 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,
2014 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.
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Bristol-Myers Squibb CompanyMedia:Carrie Fernandez,
609-419-5448Cell:
215-859-2605carrie.fernandez@bms.comorInvestors:Ranya Dajani,
609-252-5330ranya.dajani@bms.comorBill Szablewski,
609-252-5894william.szablewski@bms.com
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