dimanche 28 février 2021


Opdivo (nivolumab) Demonstrates Long Term Survival Benefit in Patients with Previously Treated Non-Squamous Non-Small Cell Lung Cancer in CheckMate -057

Par Rédaction , dans Communiqués , le 28 septembre 2015

Sunday, September 27th 2015 at 10:01pm UTC

Opdivo is the first and only PD-1 inhibitor to demonstrate
superior overall survival versus docetaxel in non-squamous non-small
cell lung cancer, with an 18-month overall survival rate of 39%

Longer term data from CheckMate -057 show benefit
with
Opdivo in overall population with greater magnitude
of survival benefit among PD-L1 expressors

Safety and tolerability profile of Opdivo is
favorable versus docetaxel and consistent with prior
Opdivo
studies

Results from CheckMate -057 published in the New England Journal
of Medicine

PRINCETON, N.J.–(BUSINESS WIRE)– Bristol-Myers
Squibb Company
 (NYSE:BMY) today announced longer term (18 month)
survival data from CheckMate -057, an open-label, randomized Phase 3
study evaluating Opdivo (n=292) versus docetaxel (n=290) in
previously treated patients with advanced, non-squamous (NSQ) non-small
cell lung cancer (NSCLC). Opdivo continued to demonstrate
superior overall survival (OS) – the study’s primary endpoint – with an
estimated 39% of patients alive at 18 months (95% CI, 34-45) versus 23%
for docetaxel, based on a minimum follow-up of 17.1 months. Opdivo
also continued to demonstrate a reduction in the risk of death by 28% (a
hazard ratio of 0.72; 95% CI, 0.60 – 0.88). In the study, Grade 3-4
treatment-related adverse events were reported in 10% of patients
treated with Opdivo versus 54% in the docetaxel arm. These data
will be presented on Monday, September 28 during the 2015 European
Cancer Congress (ECC 2015) (Abstract # 3010) and published in the New
England Journal of Medicine
.

“These longer term survival results for nivolumab in advanced,
non-squamous non-small cell lung cancer support the potential for this
Immuno-Oncology agent in treating lung cancer patients,” said Leora
Horn, M.D., Vanderbilt-Ingram Cancer Center. “CheckMate -057 builds upon
its critical findings and now, data show a sustained survival benefit
for nivolumab in this hard-to-treat disease that is incredibly
encouraging for oncologists, and most importantly, for our patients.”

CheckMate -057 clinical results were first reported at the 51st Annual
Meeting of the American Society of Clinical Oncology, marking the first
time a PD-1 inhibitor demonstrated superior OS versus docetaxel in
previously treated patients with NSQ NSCLC. Data from this trial have
been accepted for regulatory review by the U.S. Food and Drug
Administration (FDA) and the European Medicines Agency to expand the
respective Opdivo indications to include previously treated
patients with NSQ NSCLC. This application has also been granted Priority
Review in the U.S., and Opdivo has received Breakthrough
Therapy Designation for this indication.

“At the core of our Immuno-Oncology approach is an unrelenting focus to
fundamentally change survival expectations for all cancer patients.
Today, we are driving insights into how advanced lung cancer may be
treated – from defining the role of PD-L1 expression to showing clinical
efficacy resulting in deep and durable responses for these patients,”
said Michael Giordano, senior vice president, head of Development,
Oncology. “The 18-month data from CheckMate -057 reinforce the potential
for Opdivo, across PD-L1 expression levels, to offer
patients durable overall survival benefit with lower incidence of
serious adverse events versus chemotherapy.”

About CheckMate -057

CheckMate -057 is a Phase 3, open-label, randomized clinical trial that
evaluated patients with advanced NSQ 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 (ORR) and progression-free survival
(PFS). Patients enrolled in the trial received Opdivo 3
mg/kg every two weeks versus standard of care, docetaxel, at 75 mg/m2
every three weeks. In the trial, Opdivo demonstrated continued
superior OS benefit, with an estimated 51% of patients alive at one year
versus 39% for docetaxel, and an estimated 39% of patients alive at 18
months (95% CI, 34-45) versus 23% for docetaxel, based on a minimum
follow-up of 17.1 months.

CheckMate -057 also evaluated the efficacy of Opdivo by
tumor PD-L1 expression. Of randomized patients, 78% (455/582) had tumor
samples evaluable for PD-L1 expression. Rates of PD-L1 expressing tumors
were balanced between groups. PD-L1 status was predictive for benefit
from Opdivo, across pre-specified 1%, 5%, and 10%
expression levels. In PD-L1 non-expressors, OS was similar between Opdivo
and docetaxel, with improved durability of responses seen in patients
treated with Opdivo versus docetaxel.

In addition, clinical results showed confirmed ORR was significantly
higher for Opdivo (19%) than docetaxel (12%). For patients
administered Opdivo, median duration of response was 17.2 months
and 5.6 months for docetaxel. One-year PFS was 19% for Opdivo
(95% CI, 14-23) and 8% for docetaxel (95% CI, 5-12). Median PFS was 2.3
months for Opdivo (95% CI, 2.2-3.3) and 4.2 months for docetaxel
(95% CI, 3.5-4.9).

The safety profile of Opdivo in CheckMate -057 was
consistent with prior studies and similar across expressors and
non-expressors. 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%; grade 3-4: 5%) 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%).

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. 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.

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 a
monotherapy or in combination with other therapies – in which more than
8,000 patients have been enrolled worldwide.

Opdivo is a programmed death-1 (PD-1) immune checkpoint
inhibitor that has received approval from the FDA as a monotherapy in
two cancer indications. 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 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. 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. On March 4, 2015, Opdivo received its second
FDA approval for the treatment of patients with metastatic squamous (SQ)
non-small cell lung cancer (NSCLC) with progression on or after
platinum-based chemotherapy. On July 20, 2015 the European Commission
approved Nivolumab BMS for the treatment of locally advanced or
metastatic SQ NSCLC after prior chemotherapy.

INDICATION

OPDIVO® (nivolumab) is indicated 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 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 U.S.
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 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.

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.
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.

Contacts

Media:
Carrie Fernandez, 215-859-2605
carrie.fernandez@bms.com
or
Investors:
Ranya
Dajani, 609-252-5330
ranya.dajani@bms.com
or
Bill
Szablewski, 609-252-5864
william.szablewski@bms.com

Source: Bristol-Myers Squibb

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