CheckMate -057 demonstrates clear role for
PD-L1 expression in non-squamous NSCLC; PD-L1 expressers (>1%)
associated with doubling of median overall survival (17 to 19
months) compared with standard of care (8 to 9 months)
Opdivo demonstrated similar efficacy and
favorable tolerability profile versus standard of care in PD-L1
non-expressers
Opdivo decreased risk of progression or
death by 27% compared to standard of care
Safety and tolerability profile of
Opdivo is consistent with prior studies and favorable versus
current standard of care
Marks second positive Phase III trial
for Opdivo in previously-treated NSCLC
Bristol-Myers Squibb Company (NYSE:BMY) today announced that
Opdivo (nivolumab) is the first PD-1 inhibitor to demonstrate
superior overall survival versus standard of care (docetaxel) in an
open-label, randomized Phase III study (CheckMate -057) evaluating
previously-treated patients with advanced, non-squamous non-small
cell lung cancer (NSCLC). A 27% reduction in the risk of
progression or death – the primary study endpoint – was reported
for Opdivo (n=292) versus docetaxel (n=290) based upon a hazard
ratio of 0.73 (96% CI, 0.59-0.89; P = 0.0015). Opdivo was
associated with a doubling of overall median survival across the
continuum of PD-L1 expression, starting at 1% level of expression,
in the trial. The safety profile of Opdivo in CheckMate -057 was
favorable versus docetaxel with grade 3–5 treatment-related adverse
events reported in 10% of patients who were treated with Opdivo
versus 54% in the docetaxel arm.
These data will be featured today, May 29, during the 51st
Annual Meeting of the American Society of Clinical Oncology (ASCO)
press briefing at 1:00 – 2:00 PM CDT and presented during a
clinical science symposium on Saturday, May 30 from 8:51 – 9:03 AM
CDT (Late Breaking Abstract #109).
“CheckMate -057 results reported today mark a milestone in the
development of new treatment options for lung cancer, as Opdivo is
the first PD-1 inhibitor to show a significant improvement in
overall survival in a Phase III trial in non-squamous non-small
cell lung cancer compared with the current standard of care,
docetaxel,” said Luis Paz-Ares, MD, Hospital Universitario Doce de
Octubre, Madrid, Spain. “Our goal with clinical cancer research is
to always look for new options that may improve upon, or in some
cases replace, current standard of care. The CheckMate -057 results
represent progress toward establishing a new standard of care that
may replace docetaxel in PD-L1 expressers.”
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% of cases. Survival rates
vary depending on the stage and type of the cancer when it is
diagnosed.
“The survival results from this Phase III trial, as well as from
CheckMate -017 in squamous NSCLC, validate the Bristol-Myers Squibb
development strategy for Opdivo to improve survival expectations
for patients with lung cancer,” said Michael Giordano, senior vice
president, Head of Development, Oncology, Bristol-Myers Squibb.
“The CheckMate -057 results defined the role for PD-L1 expression,
based upon an overall survival endpoint and showed that patients
whose tumor expressed PD-L1 at 1% or greater levels achieved a
doubling of overall survival. This represents a significant
scientific advance in non-small cell lung cancer.”
About CheckMate -057
CheckMate -057 is a landmark Phase III, open-label, randomized
clinical trial that evaluated patients with advanced non-squamous
NSCLC who had progressed during or after one prior platinum
doublet-based chemotherapy regimen. The trial included patients
regardless of their PD-L1 status. Secondary endpoints included
objective response rate, progression-free survival and efficacy by
tumor PD-L1 expression. Patients enrolled in the trial were
administered Opdivo 3 mg/kg every two weeks versus standard of
care, docetaxel, at 75 mg/m2 every three weeks.
In addition to improving overall survival, Opdivo demonstrated a
superior objective response rate of 19% versus 12% for docetaxel (P
= 0.0246). The median duration of response for Opdivo was 17.2
months versus 5.6 months for docetaxel, and median time to response
of 2.1 months vs. 2.6 months, respectively.
CheckMate -057 also evaluated the efficacy of Opdivo by tumor
PD-L1 expression. Of randomized patients, 78% (455/582) had tumor
samples allowing the assessment of PD-L1 expression. Rates of PD-L1
expressing tumors were balanced between groups. Across
pre-specified 1%, 5%, and 10% expression levels, PD-L1 status was
predictive for benefit from Opdivo. In patients with PD-L1
expressing tumors, Opdivo demonstrated improved efficacy across all
endpoints at all expression levels (chart below).
Efficacy
Summary: Median Overall Survival by PD-L1
Expression
Opdivo Docetaxel
≥1% PD-L1 expression level
HR = 0.59 (95% CI, 0.43- 0.82)
17.2 months 9.0 months
<1% PD-L1 expression level
HR = 0.90 (95% CI, 0.66- 1.24)
10.4 months 10.1 months
≥5% PD-L1 expression level
HR = 0.43 (95% CI, 0.30-0.63)
18.2 months 8.1 months
<5% PD-L1 expression level
HR = 1.01 (95% CI, 0.77- 1.34)
9.7 months 10.1 months
≥10% PD-L1 expression level
HR = 0.40 (95% CI, 0.26-0.59)
19.4 months 8.0 months
<10% PD-L1 expression level
HR = 1.00 (95% CI, 0.76- 1.31)
9.9 months 10.3 months
The safety profile of Opdivo in CheckMate -057 was consistent
with prior studies and favorable versus docetaxel. Safety profile
also was similar across expressers and non-expressers.
Treatment-related adverse events were low in severity with Opdivo
and occurred less frequently (any grade: 69%; grade 3–4: 10%) than
docetaxel (any grade: 88%; grade 3–4: 54%), including both
hematologic and non-hematologic toxicities. Treatment-related
serious adverse events were reported less frequently with Opdivo
(any grade: 7.3%; grade 3–4: 5.2%) than docetaxel (any grade: 20%;
grade 3–4: 18%). Discontinuation due to treatment–related adverse
events was less frequent with Opdivo (5%) than docetaxel (15%).
Proven Efficacy Across Histologies in
Lung Cancer
CheckMate -057 is the second positive Phase III trial to
demonstrate superior overall survival for Opdivo in non-small cell
lung cancer. Earlier this year, the Phase III CheckMate -017 trial
was stopped early due to superior overall survival versus docetaxel
in previously-treated advanced squamous non-small cell lung cancer
and formed the basis of the company’s first indication in lung
cancer from the U.S. Food & Drug Administration’s (FDA)
approval for Opdivo. Trial results from CheckMate -017 will be
presented at ASCO during an oral abstract session on Sunday, May 31
from 4:30 – 4:42 PM CDT (Abstract #8009).
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 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 (NSCLC) 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.
View source
version on businesswire.com: http://www.businesswire.com/news/home/20150529005939/en/
Bristol-Myers Squibb CompanyMedia:Carrie Fernandez,
215-859-2605, carrie.fernandez@bms.comorInvestors:Ranya
Dajani, 609-252-5330, ranya.dajani@bms.comBill Szablewski,
609-252-5864, william.szablewski@bms.com
Bristol Myers Squibb (NYSE:BMY)
Historical Stock Chart
From Aug 2024 to Sep 2024
Bristol Myers Squibb (NYSE:BMY)
Historical Stock Chart
From Sep 2023 to Sep 2024