Opdivo is the first and only immuno-oncology therapy proven to extend survival in patients treated with one prior therapy
CheckMate -017 achieved the benchmark goal of improving overall survival in previously treated squamous non-small cell lung cancer (NSCLC)
Bristol-Myers
Squibb Company (NYSE:BMY) today announced that the U.S. Food and
Drug Administration (FDA) has approved Opdivo (nivolumab)
injection, for intravenous use, for the treatment of patients with
metastatic squamous non-small cell lung cancer (NSCLC) with progression
on or after platinum-based chemotherapy. Opdivo is the first and
only PD-1 (programmed death receptor-1) therapy to demonstrate overall
survival in previously treated metastatic squamous NSCLC. Opdivo demonstrated
significantly superior overall survival (OS) vs. docetaxel, with a 41%
reduction in the risk of death (hazard ratio: 0.59 [95% CI: 0.44, 0.79;
p=0.00025]), in a prespecified interim analysis of a Phase III clinical
trial. The median OS was 9.2 months in the Opdivo arm (95% CI:
7.3, 13.3) and 6 months in the docetaxel arm (95% CI: 5.1, 7.3).
“Bristol-Myers Squibb is committed to patients with lung cancer, and we
are pleased to offer Opdivo as the first immuno-oncology therapy
for patients who have previously treated metastatic squamous NSCLC,”
said Lamberto
Andreotti, chief executive officer, Bristol-Myers Squibb. “Because
lung cancer is one of the most commonly diagnosed cancers in the United
States, with high mortality, there is a significant need for treatments
that extend survival. We’re thankful to the many patients and healthcare
providers that partnered with us to develop a new treatment that has the
potential to address that unmet need.”
This approval is the second for Opdivo in the United States
within three months, and is based on the results of CheckMate -017 and
CheckMate -063.
Opdivo is associated with immune-mediated: pneumonitis, colitis,
hepatitis, nephritis and renal dysfunction, hypothyroidism and
hyperthyroidism, other adverse reactions; and embryofetal toxicity.
Please see the Important Safety Information section below.
Proven Superior Survival vs. Standard of Care in a Phase III Clinical
Trial
CheckMate -017 was a landmark Phase III, open-label, randomized,
multinational, multicenter clinical trial that evaluated Opdivo
(3 mg/kg intravenously over 60 minutes every two weeks) (n=135) vs.
standard of care, docetaxel (75 mg/m2 intravenously administered every 3
weeks) (n=137), in patients with metastatic squamous NSCLC who had
progressed during or after prior platinum doublet-based chemotherapy
regimen. This trial included patients regardless of their PD-L1
(programmed death ligand-1) status. The primary endpoint of this trial
was overall survival (OS).
In January, the trial was stopped based on an assessment conducted by
the independent Data Monitoring Committee (DMC), which concluded that
the study met its endpoint, demonstrating superior OS in patients
receiving Opdivo compared to docetaxel. The prespecified interim
analysis was conducted when 199 events (86% of the planned number of
events for final analysis) were observed (86 in the Opdivo arm
and 113 in the docetaxel arm).
Opdivo is the only FDA-approved monotherapy to demonstrate proven
superior OS compared to standard of care in more than 15 years in
previously treated metastatic squamous NSCLC. The median OS was 9.2
months in the Opdivo arm (95% CI: 7.3, 13.3) and 6 months in the
docetaxel arm (95% CI: 5.1, 7.3). The hazard ratio was 0.59 (95% CI:
0.44, 0.79; p=0.00025). This hazard ratio translates to a 41% reduction
in the risk of death with Opdivo compared to docetaxel.
“The FDA approval of Opdivo introduces an entirely new treatment
modality that has demonstrated unprecedented results for the treatment
of previously treated metastatic squamous NSCLC, with the potential to
replace chemotherapy for these patients,” said Dr. Suresh Ramalingam,
MD, Professor and Director of Medical Oncology, Winship Cancer Institute
of Emory University. “This milestone brings to fruition the long-held
hope that immuno-oncology medicines can be significantly effective in
this difficult-to-treat population.”
About the CheckMate -063 Trial and the Safety Profile of Opdivo
The safety profile of Opdivo in squamous NSCLC was established in
CheckMate -063, a Phase II single-arm, open-label, multinational,
multicenter trial of Opdivo, administered as a single agent in
patients with metastatic squamous NSCLC who have progressed after
receiving a platinum-based therapy and at least one additional systemic
treatment regimen (n=117). Patients received 3 mg/kg of Opdivo administered
intravenously over 60 minutes every 2 weeks. This trial included
patients regardless of their PD-L1 status. The most common
adverse reactions (reported in ≥20% of patients) were fatigue (50%),
dyspnea (38%), musculoskeletal pain (36%), decreased appetite (35%),
cough (32%), nausea (29%), and constipation (24%). Serious adverse
reactions occurred in 59% of patients receiving Opdivo. The most
frequent serious adverse reactions reported in ≥2% of patients were
dyspnea, pneumonia, chronic obstructive pulmonary disease exacerbation,
pneumonitis, hypercalcemia, pleural effusion, hemoptysis, and pain. Opdivo
was discontinued due to adverse reactions in 27% of patients.
Twenty-nine percent of patients receiving Opdivo had a drug delay
for an adverse reaction.
With at least 10 months of minimum follow up for all patients, the
confirmed objective response rate (ORR), the study’s primary endpoint,
was 15% (17/117) (95% CI = 9, 22) of which all were partial responses.
The median time to onset of response was 3.3 months (range: 1.7 to 8.8
months) after the start of Opdivo treatment. Seventy-six percent
of Opdivo responders (13/17 patients) had ongoing responses with
durability of response ranging from 1.9+ to 11.5+ months; 10 of these 17
(59%) patients had durable responses of 6 months or longer.
“The approval of Opdivo for the treatment of previously treated
metastatic squamous non-small cell lung cancer is a major advancement in
delivering extended survival for patients fighting this deadly disease,"
said Andrea Ferris, President and Chairman, Lungevity Foundation. “We
are very excited for an immuno-oncology therapy to enter the market and
offer options and hope for many of our patients. I applaud the FDA and
Bristol-Myers Squibb for their work in making this important and first
of its kind treatment available to patients so quickly.”
About Lung Cancer
Lung cancer is one of the leading causes of cancer deaths in the United
States. NSCLC is one of the most common types of the disease and
accounts for approximately 85 percent of cases. Squamous cell NSCLC
accounts for approximately 25 to 30 percent of all lung cancers.
Survival rates vary depending on the stage and type of the cancer and
when it is diagnosed. For Stage IV NSCLC, the five-year survival rate is
one percent.
About Bristol-Myers Squibb’s Patient Support Programs for Opdivo
Bristol-Myers Squibb remains committed to helping patients through
treatment with Opdivo. For support and assistance, patients and
physicians may call 1-855-OPDIVO-1. This number offers one-stop access
to a range of support services for patients and healthcare professionals
alike.
About Bristol-Myers Squibb’s Access Support
Bristol-Myers Squibb is committed to helping patients access Opdivo
and offers numerous programs to support patients and providers in
gaining access. BMS Access Support®, the Bristol-Myers Squibb
Reimbursement Services program, is designed to support access to BMS
medicines and expedite time to therapy through reimbursement support
including Benefit Investigations, Prior Authorization Facilitation,
Appeals Assistance, and assistance for patient out-of-pocket costs. BMS
Access Support assists patients and providers throughout the treatment
journey – whether it is at initial diagnosis or in support of transition
from a clinical trial. More information about our reimbursement support
services can be obtained by calling 1-800-861-0048 or by visiting www.bmsaccesssupport.com.
For healthcare providers seeking Opdivo specific reimbursement
information, please visit the BMS Access Support Product section by
visiting www.bmsaccesssupportopdivo.com.
About the Opdivo Clinical Development Program
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.
Indication and Important Safety Information for OPDIVO®
(nivolumab)
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 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.
Other 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 here.
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 CompanyMedia:Carrie Fernandez, 609-419-5448cell: 215-859-2605carrie.fernandez@bms.comorChrissy Trank, 609-419-5497cell: 732-551-5343christina.trank@bms.comorInvestors:John Elicker, 609-252-4611john.elicker@bms.comorRanya Dajani, 609-252-5330ranya.dajani@bms.com