Bristol-Myers
Squibb Company (NYSE:BMY) today announced results from CheckMate
-017, a Phase III, open-label, randomized study evaluating Opdivo
(n=135) versus docetaxel (n=137) in previously treated patients with
advanced squamous non-small cell lung cancer. At one year, Opdivo
demonstrated an overall survival rate of 42% versus 24% for docetaxel,
with a median overall survival of 9.2 months versus 6 months,
respectively. In the trial, Opdivo reduced the risk of death by
41%, based upon a hazard ratio of 0.59 (95% CI, 0.44-0.79; P = 0.00025).
The safety profile of Opdivo in CheckMate -017 was consistent
with prior studies and favorable versus docetaxel. Findings from
CheckMate -017 were published today in The New England Journal of
Medicine and presented during an oral abstract session at the 51st
Annual Meeting of the American Society of Clinical Oncology (Abstract
#8009).
“Historically, treatment options for lung cancer patients have been
limited. The Opdivo data presented today offer patients the first
major advance in the treatment of squamous non-small cell lung cancer in
more than a decade,” said David Spigel, MD, Sarah Cannon Research
Institute. “In this study, Opdivo not only demonstrated superior
overall survival and objective response rate versus chemotherapy, the
standard of care, but these benefits were sustained over time. The study
also showed that squamous non-small cell lung cancer has a unique
biology that resulted in similar efficacy across levels of PD-L1
expression.”
Opdivo demonstrated a consistent statistically significant
superiority over docetaxel across all secondary endpoints including
overall response rate and progression-free survival. Results showed that
at one year, Opdivo improved progression-free survival (21%)
versus docetaxel (6.4%). Median progression-free survival was 3.5 months
for Opdivo and 2.8 months for docetaxel, with a hazard ratio of
0.62 (95% CI, 0.47-0.81; P = 0.0004). Opdivo also
produced a significantly higher confirmed objective response rate (20%)
versus docetaxel (8.8%) (95% CI; P=0.0083). Responses for Opdivo
were ongoing and the median duration of response was not reached (range
2.9 to 21+ months) with at least 11 months of follow-up; the median
duration of response for docetaxel was 8.4 months (range 1.4+ to 15+
months).
“The results from CheckMate -017 are an important milestone in cancer
research. This study marked the first time a PD-1 immune checkpoint
inhibitor demonstrated a survival benefit in lung cancer, thereby
establishing a new treatment modality for the disease,” said Michael
Giordano, senior vice president, Head of Development, Oncology. “The
results announced today also build on and confirm our clinical research
approach to understanding the role of PD-L1 expression and degree of
benefit for Opdivo across histologies and etiologies in non-small
cell lung cancer. This is incredibly encouraging news as we continue to
study potential new options that may improve upon, and potentially
replace, the current standard of care.”
About CheckMate -017
CheckMate -017 was a Phase III, open-label, randomized clinical trial
that evaluated Opdivo 3 mg/kg intravenously over 60 minutes
every two weeks versus standard of care, docetaxel 75 mg/m2
intravenously administered every 3 weeks in patients with advanced
squamous non-small cell lung cancer who had progressed during or after
one prior platinum doublet-based chemotherapy regimen. The study’s
primary endpoint was overall survival and secondary endpoints included
progression-free survival and response rate. The trial included patients
regardless of their PD-L1 (programmed death ligand-1) expression status.
Of randomized patients in the trial (n=272), 83% (225) had quantifiable
PD-L1 expression. Rates of PD-L1 positivity were balanced between
treatment groups. Across pre-specified expression levels (1%, 5%, and
10%), Opdivo demonstrated superior benefit across all endpoints
independent of PD-L1 expression. Overall and progression-free survival
among PD-L1 subgroups favored Opdivo and was similar to the
primary population. Similar objective response rates were observed in
patients with high and low, or no PD-L1 expression, and were
consistently higher for Opdivo versus docetaxel.
The safety profile of Opdivo in CheckMate -017 was consistent
with prior studies and favorable versus docetaxel. Treatment-related
adverse events occurred less frequently with Opdivo (any grade,
58%; grade 3–4, 6.9%; no grade 5 events) than docetaxel (any grade, 86%;
grade 3–4, 55%; grade 5, 2.3%), including both hematologic and
non-hematologic toxicities.
About Non-Small Cell Lung Cancer
Lung cancer is the leading cause of cancer deaths globally, resulting in
more than 1.5 million deaths each year, according to the World Health
Organization. Lung cancer results in more deaths worldwide than
colorectal, breast and prostate cancers combined. Non-small cell lung
cancer is one of the most common types of the disease and accounts for
approximately 85 percent of cases. Survival rates vary depending on the
stage and type of the cancer when it is diagnosed. Globally, the
five-year survival rate for Stage I non-small cell lung cancer is
between 47 and 50 percent; for Stage IV non-small cell lung cancer, the
five-year survival rate drops to two percent.
About Opdivo
Bristol-Myers Squibb has a broad, global development program to study Opdivo
in multiple tumor types consisting of more than 50 trials – as
monotherapy or in combination with other therapies – in which more than
8,000 patients have been enrolled worldwide.
Opdivo became the first PD-1 immune checkpoint inhibitor to
receive regulatory approval anywhere in the world on July 4, 2014 when
Ono Pharmaceutical Co. announced that it received manufacturing and
marketing approval in Japan for the treatment of patients with
unresectable melanoma. In the U.S., the U.S. Food and Drug
Administration (FDA) granted its first approval for Opdivo for
the treatment of patients with unresectable or metastatic melanoma and
disease progression following Yervoy (ipilimumab) and, if BRAF
V600 mutation positive, a BRAF inhibitor. On March 4, 2015, Opdivo
received its second FDA approval for the treatment of patients with
metastatic squamous non-small cell lung cancer with progression on or
after platinum-based chemotherapy.
IMPORTANT SAFETY INFORMATION
Immune-Mediated Pneumonitis
-
Severe pneumonitis or interstitial lung disease, including fatal
cases, occurred with OPDIVO treatment. Across the clinical trial
experience in 691 patients with solid tumors, fatal immune-mediated
pneumonitis occurred in 0.7% (5/691) of patients receiving OPDIVO; no
cases occurred in Trial 3. In Trial 3, immune-mediated pneumonitis
occurred in 6% (7/117) of patients receiving OPDIVO including five
Grade 3 and two Grade 2 cases. Monitor patients for signs and symptoms
of pneumonitis. Administer corticosteroids for Grade 2 or greater
pneumonitis. Permanently discontinue OPDIVO for Grade 3 or 4 and
withhold OPDIVO until resolution for Grade 2.
Immune-Mediated Colitis
-
In Trial 3, diarrhea occurred in 21% (24/117) of patients receiving
OPDIVO. Grade 3 immune-mediated colitis occurred in 0.9% (1/117) of
patients. Monitor patients for immune-mediated colitis. Administer
corticosteroids for Grade 2 (of more than 5 days duration), 3, or 4
colitis. Withhold OPDIVO for Grade 2 or 3. Permanently discontinue
OPDIVO for Grade 4 colitis or recurrent colitis upon restarting OPDIVO.
Immune-Mediated Hepatitis
-
In Trial 3, the incidences of increased liver test values were AST
(16%), alkaline phosphatase (14%), ALT (12%), and total bilirubin
(2.7%). Monitor patients for abnormal liver tests prior to and
periodically during treatment. Administer corticosteroids for Grade 2
or greater transaminase elevations. Withhold OPDIVO for Grade 2 and
permanently discontinue OPDIVO for Grade 3 or 4 immune-mediated
hepatitis.
Immune-Mediated Nephritis and Renal Dysfunction
-
In Trial 3, the incidence of elevated creatinine was 22%.
Immune-mediated renal dysfunction (Grade 2) occurred in 0.9% (1/117)
of patients. Monitor patients for elevated serum creatinine prior to
and periodically during treatment. For Grade 2 or 3 serum creatinine
elevation, withhold OPDIVO and administer corticosteroids; if
worsening or no improvement occurs, permanently discontinue OPDIVO.
Administer corticosteroids for Grade 4 serum creatinine elevation and
permanently discontinue OPDIVO.
Immune-Mediated Hypothyroidism and Hyperthyroidism
-
In Trial 3, hypothyroidism occurred in 4.3% (5/117) of patients
receiving OPDIVO. Hyperthyroidism occurred in 1.7% (2/117) of patients
including one Grade 2 case. Monitor thyroid function prior to and
periodically during treatment. Administer hormone replacement therapy
for hypothyroidism. Initiate medical management for control of
hyperthyroidism.
Immune-Mediated Adverse Reactions
-
The following clinically significant immune-mediated adverse reactions
occurred in <2% of OPDIVO-treated patients: adrenal insufficiency,
uveitis, pancreatitis, facial and abducens nerve paresis,
demyeliniation, autoimmune neuropathy, motor dysfunction and
vasculitis. Across clinical trials of OPDIVO administered at doses 3
mg/kg and 10 mg/kg, additional clinically significant, immune-mediated
adverse reactions were identified: hypophysitis, diabetic
ketoacidosis, hypopituitarism, Guillain-Barré syndrome, and myasthenic
syndrome. Based on the severity of adverse reaction, withhold OPDIVO,
administer high-dose corticosteroids, and, if appropriate, initiate
hormone- replacement therapy.
Embryofetal 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 OPDIVO 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
OPDIVO, advise women to discontinue breastfeeding during treatment.
Serious Adverse Reactions
-
In Trial 3, serious adverse reactions occurred in 59% of patients
receiving OPDIVO. The most frequent serious adverse drug reactions
reported in ≥2% of patients were dyspnea, pneumonia, chronic
obstructive pulmonary disease exacerbation, pneumonitis,
hypercalcemia, pleural effusion, hemoptysis, and pain.
Common Adverse Reactions
-
The most common adverse reactions (≥20%) reported with OPDIVO in Trial
3 were fatigue (50%), dyspnea (38%), musculoskeletal pain (36%),
decreased appetite (35%), cough (32%), nausea (29%), and constipation
(24%).
Please see U.S. Full Prescribing Information for OPDIVO available at www.bms.com.
Immuno-Oncology at Bristol-Myers Squibb
Surgery, radiation, cytotoxic or targeted therapies have represented the
mainstay of cancer treatment over the last several decades, but
long-term survival and a positive quality of life have remained elusive
for many patients with advanced disease.
To address this unmet medical need, Bristol-Myers Squibb is leading
research in an innovative field of cancer research and treatment known
as Immuno-Oncology, which involves agents whose primary mechanism is to
work directly with the body’s immune system to fight cancer. The company
is exploring a variety of compounds and immunotherapeutic approaches for
patients with different types of cancer, including researching the
potential of combining Immuno-Oncology agents that target different
pathways in the treatment of cancer.
Bristol-Myers Squibb is committed to advancing the science of
Immuno-Oncology, with the goal of changing survival expectations and the
way patients live with cancer.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global pharmaceutical 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 follow us on Twitter at http://twitter.com/bmsnews.
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 lung cancer or, if
approved, that it will become commercially successful. 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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