Nivolumab is the first PD-1 immune checkpoint inhibitor to receive
a positive opinionfrom the CHMP in advanced non-small
cell lung cancer
Opinion based on overall survival benefit demonstrated in
CheckMate -017
CHMP positive opinion marks the second for nivolumab; positive
opinion for advanced melanoma was received in April 2015
Company Website:
http://www.bms.com
PRINCETON, N.J. -- (Business Wire)
Bristol-Myers
Squibb Company (NYSE:BMY) today announced that the Committee for
Medicinal Products for Human Use (CHMP) of the European Medicines Agency
(EMA) has adopted a positive opinion recommending that nivolumab, a
PD-1 immune checkpoint inhibitor, be granted approval for the treatment
of locally advanced or metastatic squamous non-small cell lung cancer
(NSCLC) after prior chemotherapy in adults. The CHMP positive opinion
will now be reviewed by the European Commission, which has the authority
to approve medicines for the European Union (EU).
“We are moving at a ground-breaking pace to deliver on a mission that
looks to transform cancer treatment options for patients,” said Michael
Giordano, senior vice president, Head of Development, Oncology. “Last
month, we received a CHMP positive opinion for nivolumab for the
treatment of advanced melanoma. Today’s announcement of a positive
opinion for nivolumab in NSCLC brings us closer to delivering on our
promise of changing the standard of care for lung cancer.”
Positive Opinion based on CheckMate -017 and
-063
The CHMP positive opinion is based on data from CheckMate -017 and
CheckMate -063, two trials that demonstrated the efficacy and safety of
nivolumab in patients with advanced or metastatic squamous NSCLC who had
progressed following previous chemotherapy treatment. CheckMate -017 was
a Phase III, randomized, open-label trial that included patients who had
experienced disease progression during or after one prior platinum
doublet-based chemotherapy regimen.
Results from a prespecified interim analysis of CheckMate -017,
demonstrated significantly superior overall survival (OS) with nivolumab
vs. docetaxel, with a 41% reduction in the risk of death (hazard ratio:
0.59 [95% CI: 0.44, 0.79; p=0.00025]). This benefit was observed
regardless of PD-L1 expression status. The estimated one-year survival
rate was nearly doubled with nivolumab (42% [95% CI: 34, 50]) compared
to docetaxel (24% [95% CI: 17, 31]). The median OS was 9.2 months in the
nivolumabarm (95% CI: 7.3, 13.3) and 6 months in the docetaxel
arm (95% CI: 5.1, 7.3).
A second study, CheckMate -063, was a Phase II single-arm,
multinational, multicenter trial that included patients with metastatic
squamous NSCLC who had progressed after receiving a platinum-based
therapy and at least one additional systemic treatment regimen (65% of
patients had received ≥ 3 prior therapies). In CheckMate -063, confirmed
objective response rate, the study’s primary endpoint, was 14.5%
(17/117) (95% CI = 8.7, 22.2) with an estimated one-year survival rate
of 40.8% (95% CI: 31.6, 49.7) and median overall survival of 8.2 months
(95% CI: 6.1, 10.9).
In both CheckMate -017 and -063, there was consistent nivolumab dosing
of 3 mg/kg every two weeks. The safety profile of nivolumab has been
evaluated in thousands of patients enrolled in the broader clinical
program and treatment-related adverse events (AEs) were generally
managed using established safety algorithms. In CheckMate -017, the
safety profile of nivolumab was consistent with prior studies and
favorable versus docetaxel. Treatment-related adverse events occurred
less frequently with nivolumab than docetaxel (grade 3–4, 6.9% vs. 55%,
respectively).
About Nivolumab
Bristol-Myers Squibb has a broad, global development program to study
nivolumab 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.
Nivolumab 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 nivolumab 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, nivolumab
received its second FDA approval for the treatment of patients with
metastatic squamous non-small cell lung cancer (NSCLC) with progression
on or after platinum-based chemotherapy.
In addition, nivolumab is being investigated in patients with advanced
non-squamous NSCLC. On April 17, 2015, an open-label, randomized Phase
III study (CheckMate -057) evaluating nivolumab versus docetaxel in
previously treated patients with advanced non-squamous 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 nivolumab compared to
docetaxel. The company plans to share these data with health authorities.
About 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. 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.
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 1 or Trial 3. 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. 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 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. 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 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. 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 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. 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 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. 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.
Other Immune-Mediated Adverse Reactions
-
In Trial 1 and 3 (n=385), 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 1, 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 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
1 were rash (21%) and in Trial 3 were fatigue (50%), dyspnea (38%),
musculoskeletal pain (36%), decreased appetite (35%), cough (32%),
nausea (29%), and constipation (24%).
Please see US
Full Prescribing Information for OPDIVO.
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 nivolumab will receive
regulatory approval in the European Union or, if approved, that it will
become a commercially successful product. 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.
View source version on businesswire.com: http://www.businesswire.com/news/home/20150522005319/en/
Contacts:
Bristol-Myers Squibb
Media:
Carrie Fernandez,
215-859-2605
carrie.fernandez@bms.com
or
Investors:
Ranya
Dajani, 609-252-5330
ranya.dajani@bms.com
Source: Bristol-Myers Squibb Company
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