CheckMate -017, A Phase 3 Study of Opdivo (Nivolumab) Compared to Docetaxel in Patients with Second-Line Squamous Cell Non-sm...
January 11 2015 - 9:06PM
Business Wire
Opdivo demonstrates superior
overall survival in this Phase 3 trial
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.
Bristol-Myers Squibb CompanyMedia:Carrie
Fernandez, 609-419-5448Cell:
215-859-2605carrie.fernandez@bms.comorInvestors:Ranya
Dajani, 609-252-5330ranya.dajani@bms.comorRyan Asay,
609-252-5020ryan.asay@bms.com
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