Bristol-Myers
Squibb Company (NYSE:BMY) today announced that an open-label,
randomized Phase 3 study evaluating Opdivo versus docetaxel in
previously treated patients with advanced, squamous cell non-small cell
lung cancer (NSCLC) was stopped early because an assessment conducted by
the independent Data Monitoring Committee (DMC) concluded that the study
met its endpoint, demonstrating superior overall survival in patients
receiving Opdivo compared to the control arm. The company will
share these data – which for the first time indicate a survival
advantage with an anti-PD1 immune checkpoint inhibitor in lung cancer –
with health authorities.
CheckMate -017 investigators are being informed of the decision to stop
the comparative portion of the trial. Bristol-Myers Squibb is working to
ensure that eligible patients will be informed of the opportunity to
continue or start treatment with Opdivo in an open-label
extension 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 -017 data
and work with investigators on the future presentation and publication
of the results.
About the Study
CheckMate -017 is a Phase 3, open-label, randomized study of Opdivo
versus docetaxel in previously treated patients with advanced or
metastatic squamous cell NSCLC. The trial randomized 272 patients to
receive either nivolumab 3 mg/kg intravenously every two weeks or
docetaxel 75 mg/m2 intravenously every three weeks. The primary endpoint
is overall survival. Secondary endpoints include objective response rate
and progression free survival.
About Lung Cancer
Lung cancer is the leading cause of cancer deaths globally, resulting in
more than 1.5 million deaths each year according the World Health
Organization. NSCLC 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 NSCLC is between 47
and 50 percent; for Stage IV NSCLC, the five-year survival rate drops to
two percent. Historically, the expected one-year survival rate for
third-line squamous cell NSCLC patients is approximately 5.5% - 18%.
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 and
complementary 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 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 7,000
patients have been enrolled worldwide.
In the U.S., Opdivo is indicated 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. 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.
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 574 patients with solid tumors, fatal immune-mediated
pneumonitis occurred in 0.9% (5/574) of patients receiving OPDIVO; no
cases occurred in Trial 1. In Trial 1, pneumonitis, including
interstitial lung disease, occurred in 3.4% (9/268) of patients
receiving OPDIVO and none of the 102 patients receiving chemotherapy.
Immune-mediated pneumonitis occurred in 2.2% (6/268) of patients
receiving OPDIVO; one with Grade 3 and five with Grade 2. 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 1, diarrhea or colitis occurred in 21% (57/268) of patients
receiving OPDIVO and 18% (18/102) of patients receiving chemotherapy.
Immune-mediated colitis occurred in 2.2% (6/268) of patients receiving
OPDIVO; five with Grade 3 and one with Grade 2. 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 1, there was an increased incidence of liver test
abnormalities in the OPDIVO-treated group as compared to the
chemotherapy-treated group, with increases in AST (28% vs 12%),
alkaline phosphatase (22% vs 13%), ALT (16% vs 5%), and total
bilirubin (9% vs 0). Immune-mediated hepatitis occurred in 1.1%
(3/268) of patients receiving OPDIVO; two with Grade 3 and one with
Grade 2. 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 1, there was an increased incidence of elevated creatinine in
the OPDIVO-treated group as compared to the chemotherapy-treated group
(13% vs 9%). Grade 2 or 3 immune-mediated nephritis or renal
dysfunction occurred in 0.7% (2/268) 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 1, Grade 1 or 2 hypothyroidism occurred in 8% (21/268) of
patients receiving OPDIVO and none of the 102 patients receiving
chemotherapy. Grade 1 or 2 hyperthyroidism occurred in 3% (8/268) of
patients receiving OPDIVO and 1% (1/102) of patients receiving
chemotherapy. Monitor thyroid function prior to and periodically
during treatment. Administer hormone replacement therapy for
hypothyroidism. Initiate medical management for control of
hyperthyroidism.
Other Immune-Mediated Adverse Reactions
-
In Trial 1, the following clinically significant, immune-mediated
adverse reactions occurred in less than 1% of OPDIVO-treated patients:
pancreatitis, uveitis, demyelination, autoimmune neuropathy, adrenal
insufficiency, and facial and abducens nerve paresis. 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,
Guillian-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
-
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.
Common Adverse Reactions
The most common adverse reaction (≥20%) reported with OPDIVO was rash
(21%).
Please see US
Full Prescribing Information for OPDIVO.
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. Ono
Pharmaceutical received manufacturing and marketing approval in Japan
for Opdivo in July 2014 for the treatment of patients with
unresectable melanoma, making Opdivo the first PD-1 immune
checkpoint inhibitor to receive regulatory approval anywhere in the
world.
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 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, 2013 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.
Copyright Business Wire 2015