Opdivo (nivolumab) Demonstrated Efficacy and Improved Survival in Patients with Previously
Treated Advanced Gastric Cancer in a Randomized Phase 3 Study
Opdivo demonstrated a 37% reduction in the risk of death compared to placebo
12-month overall survival rates were 26.6% in Opdivo-treated patients compared to 10.9% in
placebo-treated patients
Bristol-Myers Squibb Company (NYSE:BMY) announced today the results of ONO-4538-12 demonstrating Opdivo
(nivolumab) significantly reduced the risk of death by 37% (HR 0.63; p<0.0001) in patients with previously treated advanced
gastric cancer refractory to or intolerant of standard therapy, a condition without current standard-of-care treatments.
ONO-4538-12 is a Phase 3, randomized, double-blind, placebo-controlled clinical trial evaluating Opdivo’s efficacy and
safety in such patients. The primary endpoint of the study is overall survival (OS). Median OS was 5.32 months (95% CI: 4.63 to
6.41) for patients treated with Opdivo, compared to 4.14 months (95% CI: 3.42 to 4.86) (p<0.0001) for those treated with
placebo. In addition, the 12-month OS in the Opdivo group was 26.6% (95% CI: 21.1 to 32.4) versus 10.9% (95% CI: 6.2 to
17.0) in the placebo group. Patients treated with Opdivo also experienced an objective response rate of 11.2% (95% CI: 7.7
to 15.6) compared to 0% (95% CI: 0.0 to 2.8) with placebo and a median duration of response of 9.53 months (95% CI: 6.14 to 9.82),
which were secondary endpoints.
The safety profile of Opdivo was consistent with previously reported studies in solid tumors. Treatment-related adverse
events (TRAEs) of any grade and Grade 3/4 occurred in 42.7% versus 26.7% and 10.3% versus 4.3% of Opdivo-treated and
placebo-treated patients, respectively. The Grade 3/4 TRAEs reported in more than 2% of patients were diarrhea, fatigue, decreased
appetite, pyrexia, as well as increased AST and ALT in the Opdivo group, and fatigue and decreased appetite in the placebo
group. The Opdivo and placebo-treated patients had similar rates of TRAEs leading to discontinuation, 2.7% and 2.5%,
respectively.
The ONO-4538-12 data are being presented today in a late-breaking oral presentation from 2:00 – 3:30 p.m. PST (Abstract #2) at
the 2017 Gastrointestinal Cancers Symposium in San Francisco, Calif.
“ONO-4538-12 is the first randomized, Phase 3 Immuno-Oncology trial to demonstrate improved survival for patients with
previously treated advanced or recurrent gastric cancer. We find these results with Opdivo encouraging, as gastric cancer is
a leading cause of cancer death globally and unmet needs remain for patients with advanced forms of this disease who become
intolerant to chemotherapy or for whom such treatment has failed,” said Ian M. Waxman, M.D., development lead, Gastrointestinal
Oncology, Bristol-Myers Squibb.
“These results show a clinical benefit with Opdivo for patients with pretreated advanced or recurrent gastric cancer and
establish a strong basis for conducting additional studies with Opdivo as a treatment for patients with gastric cancer,”
added lead study investigator Yoon-Koo Kang, M.D., Ph.D., of the Department of Oncology at the University of Ulsan College of
Medicine, Asan Medical Center in Seoul, Korea.
About ONO-4538-12
ONO-4538-12 (NCT02267343) is a Phase 3, randomized, double-blind, placebo-controlled clinical trial conducted in Japan, Korea
and Taiwan, evaluating the efficacy and safety of Opdivo in patients with unresectable (unable to be removed with surgery)
previously treated advanced or recurrent gastric cancer, including gastroesophageal junction cancer, refractory to or intolerant of
standard therapy. This trial was conducted by Ono Pharmaceutical Co. Ltd. of Japan, Bristol-Myers Squibb’s development partner for
Opdivo.
In ONO-4538-12, Opdivo 3 mg/kg or placebo was administered every two weeks until disease progression or discontinuation
due to unacceptable toxicity. The primary endpoint, OS, was assessed for the superiority of Opdivo versus placebo. The
secondary endpoints included objective response rate, duration of response, progression free survival, best overall response, time
to response, disease control rate and safety measures.
About Gastric Cancer
Gastric cancer, also known as stomach cancer, is the fifth most common malignancy in the world, with more than 950,000 patients
diagnosed each year, and is the third leading cause of cancer-related death, with more than 720,000 deaths reported annually. The
prevalence of gastric cancer is higher in East Asian countries than in Western countries. While the five-year survival rate for
people with gastric cancer is 30.4%, this rate falls to approximately 5% for those whose gastric cancer has metastasized (or
spread). Because no standard-of-care treatment options exist for patients with unresectable advanced or recurrent gastric cancer
after chemotherapy, there remains an important unmet medical need for patients with this condition.
Bristol-Myers Squibb: At the Forefront of Immuno-Oncology Science & Innovation
At Bristol-Myers Squibb, patients are at the center of everything we do. Our vision for the future of cancer care is focused on
researching and developing transformational Immuno-Oncology (I-O) medicines that will raise survival expectations in hard-to-treat
cancers and will change the way patients live with cancer.
We are leading the scientific understanding of I-O through our extensive portfolio of investigational and approved agents,
including the first combination of two I-O agents in metastatic melanoma, and our differentiated clinical development program,
which is studying broad patient populations across more than 20 types of cancers with 11 clinical-stage molecules designed to
target different immune system pathways. Our deep expertise and innovative clinical trial designs uniquely position us to advance
the science of combinations across multiple tumors and potentially deliver the next wave of I-O combination regimens with a sense
of urgency. We also continue to pioneer research that will help facilitate a deeper understanding of the role of immune biomarkers
and inform which patients will benefit most from I-O therapies.
We understand making the promise of I-O a reality for the many patients who may benefit from these therapies requires not only
innovation on our part but also close collaboration with leading experts in the field. Our partnerships with academia, government,
advocacy and biotech companies support our collective goal of providing new treatment options to advance the standards of clinical
practice.
About Opdivo
Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own
immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo
has become an important treatment option across multiple cancers.
Opdivo’s leading global development program is based on Bristol-Myers Squibb’s scientific expertise in the field of
Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To
date, the Opdivo clinical development program has enrolled more than 25,000 patients. The Opdivo trials
have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how
patients may benefit from Opdivo across the continuum of PD-L1 expression.
In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the
world. Opdivo is currently approved in more than 60 countries, including the United States, the European Union and Japan. In
October 2015, the company’s Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to
receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including
the United States and the European Union.
U.S. FDA APPROVED INDICATIONS FOR OPDIVO ®
OPDIVO® (nivolumab) as a single agent is indicated for the treatment of patients with BRAF V600 mutation-positive
unresectable or metastatic melanoma. This indication is approved under accelerated approval based on progression-free survival.
Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory
trials.
OPDIVO® (nivolumab) as a single agent is indicated for the treatment of patients with BRAF V600 wild-type
unresectable or metastatic melanoma.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of patients
with unresectable or metastatic melanoma. This indication is approved under accelerated approval based on progression-free
survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the
confirmatory trials.
OPDIVO® (nivolumab) is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC)
with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease
progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO.
OPDIVO® (nivolumab) is indicated for the treatment of patients with advanced renal cell carcinoma (RCC) who have
received prior anti-angiogenic therapy.
OPDIVO® (nivolumab) is indicated for the treatment of patients with classical Hodgkin lymphoma (cHL) that has
relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and post-transplantation brentuximab
vedotin. This indication is approved under accelerated approval based on overall response rate. Continued approval for this
indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
OPDIVO® (nivolumab) is indicated for the treatment of patients with recurrent or metastatic squamous cell carcinoma
of the head and neck (SCCHN) with disease progression on or after platinum-based therapy.
IMPORTANT SAFETY INFORMATION
WARNING: IMMUNE-MEDIATED ADVERSE REACTIONS
YERVOY can result in severe and fatal immune-mediated adverse reactions. These immune-mediated reactions may involve any
organ system; however, the most common severe immune-mediated adverse reactions are enterocolitis, hepatitis, dermatitis (including
toxic epidermal necrolysis), neuropathy, and endocrinopathy. The majority of these immune-mediated reactions initially manifested
during treatment; however, a minority occurred weeks to months after discontinuation of YERVOY.
Assess patients for signs and symptoms of enterocolitis, dermatitis, neuropathy, and endocrinopathy and evaluate clinical
chemistries including liver function tests (LFTs), adrenocorticotropic hormone (ACTH) level, and thyroid function tests at baseline
and before each dose.
Permanently discontinue YERVOY and initiate systemic high-dose corticosteroid therapy for severe immune-mediated
reactions.
Immune-Mediated Pneumonitis
OPDIVO can cause immune-mediated pneumonitis. Fatal cases have been reported. Monitor patients for signs with radiographic
imaging and for symptoms of pneumonitis. Administer corticosteroids for Grade 2 or more severe pneumonitis. Permanently discontinue
for Grade 3 or 4 and withhold until resolution for Grade 2. In patients receiving OPDIVO monotherapy, fatal cases of
immune-mediated pneumonitis have occurred. Immune-mediated pneumonitis occurred in 3.1% (61/1994) of patients. In patients
receiving OPDIVO with YERVOY, immune-mediated pneumonitis occurred in 6% (25/407) of patients.
In Checkmate 205 and 039, pneumonitis, including interstitial lung disease, occurred in 4.9% (13/263) of patients receiving
OPDIVO. Immune-mediated pneumonitis occurred in 3.4% (9/263) of patients receiving OPDIVO: Grade 3 (n=1) and Grade 2 (n=8).
Immune-Mediated Colitis
OPDIVO can cause immune-mediated colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for
Grade 2 (of more than 5 days duration), 3, or 4 colitis. Withhold OPDIVO monotherapy for Grade 2 or 3 and permanently discontinue
for Grade 4 or recurrent colitis upon re-initiation of OPDIVO. When administered with YERVOY, withhold OPDIVO and YERVOY for Grade
2 and permanently discontinue for Grade 3 or 4 or recurrent colitis. In patients receiving OPDIVO monotherapy, immune-mediated
colitis occurred in 2.9% (58/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated colitis occurred in 26%
(107/407) of patients including three fatal cases.
In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening, or fatal (diarrhea of ≥7 stools above baseline, fever,
ileus, peritoneal signs; Grade 3-5) immune-mediated enterocolitis occurred in 34 (7%) patients. Across all YERVOY-treated patients
in that study (n=511), 5 (1%) developed intestinal perforation, 4 (0.8%) died as a result of complications, and 26 (5%) were
hospitalized for severe enterocolitis.
Immune-Mediated Hepatitis
OPDIVO can cause immune-mediated hepatitis. Monitor patients for abnormal liver tests prior to and periodically during
treatment. Administer corticosteroids for Grade 2 or greater transaminase elevations. Withhold for Grade 2 and permanently
discontinue for Grade 3 or 4 immune-mediated hepatitis. In patients receiving OPDIVO monotherapy, immune-mediated hepatitis
occurred in 1.8% (35/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated hepatitis occurred in 13%
(51/407) of patients.
In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening, or fatal hepatotoxicity (AST or ALT elevations >5x
the ULN or total bilirubin elevations >3x the ULN; Grade 3-5) occurred in 8 (2%) patients, with fatal hepatic failure in
0.2% and hospitalization in 0.4%.
Immune-Mediated Neuropathies
In a separate Phase 3 study of YERVOY 3 mg/kg, 1 case of fatal Guillain-Barré syndrome and 1 case of severe (Grade 3) peripheral
motor neuropathy were reported.
Immune-Mediated Endocrinopathies
OPDIVO can cause immune-mediated hypophysitis, immune-mediated adrenal insufficiency, autoimmune thyroid disorders, and Type 1
diabetes mellitus. Monitor patients for signs and symptoms of hypophysitis, signs and symptoms of adrenal insufficiency, thyroid
function prior to and periodically during treatment, and hyperglycemia. Administer hormone replacement as clinically indicated and
corticosteroids for Grade 2 or greater hypophysitis. Withhold for Grade 2 or 3 and permanently discontinue for Grade 4
hypophysitis. Administer corticosteroids for Grade 3 or 4 adrenal insufficiency. Withhold for Grade 2 and permanently discontinue
for Grade 3 or 4 adrenal insufficiency. Administer hormone-replacement therapy for hypothyroidism. Initiate medical management for
control of hyperthyroidism. Withhold OPDIVO for Grade 3 and permanently discontinue for Grade 4 hyperglycemia.
In patients receiving OPDIVO monotherapy, hypophysitis occurred in 0.6% (12/1994) of patients. In patients receiving OPDIVO with
YERVOY, hypophysitis occurred in 9% (36/407) of patients. In patients receiving OPDIVO monotherapy, adrenal insufficiency occurred
in 1% (20/1994) of patients. In patients receiving OPDIVO with YERVOY, adrenal insufficiency occurred in 5% (21/407) of patients.
In patients receiving OPDIVO monotherapy, hypothyroidism or thyroiditis resulting in hypothyroidism occurred in 9% (171/1994) of
patients. Hyperthyroidism occurred in 2.7% (54/1994) of patients receiving OPDIVO monotherapy. In patients receiving OPDIVO with
YERVOY, hypothyroidism or thyroiditis resulting in hypothyroidism occurred in 22% (89/407) of patients. Hyperthyroidism occurred in
8% (34/407) of patients receiving OPDIVO with YERVOY. In patients receiving OPDIVO monotherapy, diabetes occurred in 0.9% (17/1994)
of patients. In patients receiving OPDIVO with YERVOY, diabetes occurred in 1.5% (6/407) of patients.
In a separate Phase 3 study of YERVOY 3 mg/kg, severe to life-threatening immune-mediated endocrinopathies (requiring
hospitalization, urgent medical intervention, or interfering with activities of daily living; Grade 3-4) occurred in 9 (1.8%)
patients. All 9 patients had hypopituitarism, and some had additional concomitant endocrinopathies such as adrenal
insufficiency, hypogonadism, and hypothyroidism. 6 of the 9 patients were hospitalized for severe endocrinopathies.
Immune-Mediated Nephritis and Renal Dysfunction
OPDIVO can cause immune-mediated nephritis. Monitor patients for elevated serum creatinine prior to and periodically during
treatment. Administer corticosteroids for Grades 2-4 increased serum creatinine. Withhold OPDIVO for Grade 2 or 3 and permanently
discontinue for Grade 4 increased serum creatinine. In patients receiving OPDIVO monotherapy, immune-mediated nephritis and renal
dysfunction occurred in 1.2% (23/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated nephritis and renal
dysfunction occurred in 2.2% (9/407) of patients.
Immune-Mediated Skin Adverse Reactions and Dermatitis
OPDIVO can cause immune-mediated rash, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), some cases
with fatal outcome. Administer corticosteroids for Grade 3 or 4 rash. Withhold for Grade 3 and permanently discontinue for Grade 4
rash. For symptoms or signs of SJS or TEN, withhold OPDIVO and refer the patient for specialized care for assessment and treatment;
if confirmed, permanently discontinue. In patients receiving OPDIVO monotherapy, immune-mediated rash occurred in 9% (171/1994) of
patients. In patients receiving OPDIVO with YERVOY, immune-mediated rash occurred in 22.6% (92/407) of patients.
In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening, or fatal immune-mediated dermatitis (eg,
Stevens-Johnson syndrome, toxic epidermal necrolysis, or rash complicated by full thickness dermal ulceration, or necrotic,
bullous, or hemorrhagic manifestations; Grade 3-5) occurred in 13 (2.5%) patients. 1 (0.2%) patient died as a result of toxic
epidermal necrolysis. 1 additional patient required hospitalization for severe dermatitis.
Immune-Mediated Encephalitis
OPDIVO can cause immune-mediated encephalitis. Evaluation of patients with neurologic symptoms may include, but not be limited
to, consultation with a neurologist, brain MRI, and lumbar puncture. Withhold OPDIVO in patients with new-onset moderate to severe
neurologic signs or symptoms and evaluate to rule out other causes. If other etiologies are ruled out, administer corticosteroids
and permanently discontinue OPDIVO for immune-mediated encephalitis. In patients receiving OPDIVO monotherapy, encephalitis
occurred in 0.2% (3/1994) of patients. Fatal limbic encephalitis occurred in one patient after 7.2 months of exposure despite
discontinuation of OPDIVO and administration of corticosteroids. Encephalitis occurred in one patient receiving OPDIVO with YERVOY
(0.2%) after 1.7 months of exposure.
Other Immune-Mediated Adverse Reactions
Based on the severity of adverse reaction, permanently discontinue or withhold treatment, administer high-dose corticosteroids,
and, if appropriate, initiate hormone-replacement therapy. Across clinical trials of OPDIVO the following clinically significant
immune-mediated adverse reactions occurred in <1.0% of patients receiving OPDIVO: uveitis, iritis, pancreatitis, facial and
abducens nerve paresis, demyelination, polymyalgia rheumatica, autoimmune neuropathy, Guillain-Barré syndrome, hypopituitarism,
systemic inflammatory response syndrome, gastritis, duodenitis, sarcoidosis, histiocytic necrotizing lymphadenitis (Kikuchi
lymphadenitis), myositis, myocarditis, rhabdomyolysis, motor dysfunction, vasculitis, and myasthenic syndrome.
Infusion Reactions
OPDIVO can cause severe infusion reactions, which have been reported in <1.0% of patients in clinical trials. Discontinue
OPDIVO in patients with Grade 3 or 4 infusion reactions. Interrupt or slow the rate of infusion in patients with Grade 1 or 2. In
patients receiving OPDIVO monotherapy, infusion-related reactions occurred in 6.4% (127/1994) of patients. In patients receiving
OPDIVO with YERVOY, infusion-related reactions occurred in 2.5% (10/407) of patients.
Complications of Allogeneic HSCT after OPDIVO
Complications, including fatal events, occurred in patients who received allogeneic HSCT after OPDIVO. Outcomes were evaluated
in 17 patients from Checkmate 205 and 039, who underwent allogeneic HSCT after discontinuing OPDIVO (15 with reduced-intensity
conditioning, 2 with myeloablative conditioning). Thirty-five percent (6/17) of patients died from complications of allogeneic HSCT
after OPDIVO. Five deaths occurred in the setting of severe or refractory GVHD. Grade 3 or higher acute GVHD was reported in 29%
(5/17) of patients. Hyperacute GVHD was reported in 20% (n=2) of patients. A steroid-requiring febrile syndrome, without an
identified infectious cause, was reported in 35% (n=6) of patients. Two cases of encephalitis were reported: Grade 3 (n=1)
lymphocytic encephalitis without an identified infectious cause, and Grade 3 (n=1) suspected viral encephalitis. Hepatic
veno-occlusive disease (VOD) occurred in one patient, who received reduced-intensity conditioned allogeneic HSCT and died of GVHD
and multi-organ failure. Other cases of hepatic VOD after reduced-intensity conditioned allogeneic HSCT have also been reported in
patients with lymphoma who received a PD-1 receptor blocking antibody before transplantation. Cases of fatal hyperacute GVHD have
also been reported. These complications may occur despite intervening therapy between PD-1 blockade and allogeneic HSCT.
Follow patients closely for early evidence of transplant-related complications such as hyperacute GVHD, severe (Grade 3 to 4)
acute GVHD, steroid-requiring febrile syndrome, hepatic VOD, and other immune-mediated adverse reactions, and intervene
promptly.
Embryo-Fetal Toxicity
Based on their mechanisms of action, OPDIVO and YERVOY 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 an OPDIVO- or YERVOY- containing regimen and for at least 5 months after the last dose of OPDIVO.
Lactation
It is not known whether OPDIVO or YERVOY 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 an OPDIVO-containing regimen, advise
women to discontinue breastfeeding during treatment. Advise women to discontinue nursing during treatment with YERVOY and for 3
months following the final dose.
Serious Adverse Reactions
In Checkmate 037, serious adverse reactions occurred in 41% of patients receiving OPDIVO (n=268). 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 Checkmate 066, serious adverse reactions occurred in 36% of patients receiving OPDIVO (n=206). Grade 3 and 4 adverse reactions
occurred in 41% of patients receiving OPDIVO. The most frequent Grade 3 and 4 adverse reactions reported in ≥2% of patients
receiving OPDIVO were gamma-glutamyltransferase increase (3.9%) and diarrhea (3.4%). In Checkmate 067, serious adverse reactions
(73% and 37%), adverse reactions leading to permanent discontinuation (43% and 14%) or to dosing delays (55% and 28%), and Grade 3
or 4 adverse reactions (72% and 44%) all occurred more frequently in the OPDIVO plus YERVOY arm (n=313) relative to the OPDIVO arm
(n=313). The most frequent (≥10%) serious adverse reactions in the OPDIVO plus YERVOY arm and the OPDIVO arm, respectively, were
diarrhea (13% and 2.6%), colitis (10% and 1.6%), and pyrexia (10% and 0.6%). In Checkmate 017 and 057, serious adverse reactions
occurred in 46% of patients receiving OPDIVO (n=418). The most frequent serious adverse reactions reported in at least 2% of
patients receiving OPDIVO were pneumonia, pulmonary embolism, dyspnea, pyrexia, pleural effusion, pneumonitis, and respiratory
failure. In Checkmate 025, serious adverse reactions occurred in 47% of patients receiving OPDIVO (n=406). The most frequent
serious adverse reactions reported in ≥2% of patients were acute kidney injury, pleural effusion, pneumonia, diarrhea, and
hypercalcemia. In Checkmate 205 and 039, among all patients (safety population [n=263]), adverse reactions leading to
discontinuation (4.2%) or to dosing delays (23%) occurred. The most frequent serious adverse reactions reported in ≥1% of patients
were infusion-related reaction, pneumonia, pleural effusion, pyrexia, rash and pneumonitis. Ten patients died from causes other
than disease progression, including 6 who died from complications of allogeneic HSCT. Serious adverse reactions occurred in 21% of
patients in the safety population (n=263) and 27% of patients in the subset of patients evaluated for efficacy (efficacy population
[n=95]). In Checkmate 141, serious adverse reactions occurred in 49% of patients receiving OPDIVO. The most frequent serious
adverse reactions reported in at least 2% of patients receiving OPDIVO were pneumonia, dyspnea, respiratory failure, respiratory
tract infections, and sepsis.
Common Adverse Reactions
In Checkmate 037, the most common adverse reaction (≥20%) reported with OPDIVO (n=268) was rash (21%). In Checkmate 066, the
most common adverse reactions (≥20%) reported with OPDIVO (n=206) vs dacarbazine (n=205) were fatigue (49% vs 39%), musculoskeletal
pain (32% vs 25%), rash (28% vs 12%), and pruritus (23% vs 12%). In Checkmate 067, the most common (≥20%) adverse reactions in the
OPDIVO plus YERVOY arm (n=313) were fatigue (59%), rash (53%), diarrhea (52%), nausea (40%), pyrexia (37%), vomiting (28%), and
dyspnea (20%). The most common (≥20%) adverse reactions in the OPDIVO (n=313) arm were fatigue (53%), rash (40%), diarrhea (31%),
and nausea (28%). In Checkmate 017 and 057, the most common adverse reactions (≥20%) in patients receiving OPDIVO (n=418) were
fatigue, musculoskeletal pain, cough, dyspnea, and decreased appetite. In Checkmate 025, the most common adverse reactions (≥20%)
reported in patients receiving OPDIVO (n=406) vs everolimus (n=397) were asthenic conditions (56% vs 57%), cough (34% vs 38%),
nausea (28% vs 29%), rash (28% vs 36%), dyspnea (27% vs 31%), diarrhea (25% vs 32%), constipation (23% vs 18%), decreased appetite
(23% vs 30%), back pain (21% vs 16%), and arthralgia (20% vs 14%). In Checkmate 205 and 039, among all patients (safety population
[n=263]) and the subset of patients in the efficacy population (n=95), respectively, the most common adverse reactions (≥20%) were
fatigue (32% and 43%), upper respiratory tract infection (28% and 48%), pyrexia (24% and 35%), diarrhea (23% and 30%), and cough
(22% and 35%). In the subset of patients in the efficacy population (n=95), the most common adverse reactions also included rash
(31%), musculoskeletal pain (27%), pruritus (25%), nausea (23%), arthralgia (21%), and peripheral neuropathy (21%). In Checkmate
141, the most common adverse reactions (≥10%) in patients receiving OPDIVO were cough and dyspnea at a higher incidence than
investigator’s choice.
In a separate Phase 3 study of YERVOY 3 mg/kg, the most common adverse reactions (≥5%) in patients who received YERVOY at
3 mg/kg were fatigue (41%), diarrhea (32%), pruritus (31%), rash (29%), and colitis (8%).
Checkmate Trials and Patient Populations
Checkmate 067 - advanced melanoma alone or in combination with YERVOY; Checkmate 037 and 066 - advanced melanoma; Checkmate 017
- squamous non-small cell lung cancer (NSCLC); Checkmate 057 - non-squamous NSCLC; Checkmate 025 - renal cell carcinoma; Checkmate
205/039 - classical Hodgkin lymphoma; Checkmate 141 – squamous cell carcinoma of the head and neck.
Please see U.S. Full Prescribing Information, including Boxed WARNING regarding immune-mediated adverse reactions,
for YERVOY.
Please see U.S. 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 2014, Ono and Bristol-Myers Squibb 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 us
at BMS.com or follow us on LinkedIn, Twitter, YouTube and Facebook.
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
the additional indication described herein. 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, 2015 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 Company
Media:
Audrey Abernathy, 919-605-4521
audrey.abernathy@bms.com
or
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timothy.power@bms.com
or
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