In CheckMate -141, Opdivo (nivolumab) Demonstrated Sustained Overall Survival (OS) Advantage over Standard of Care in Patients with Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Patients treated with Opdivo experienced a 32%
reduction in the risk of death after two years minimum follow-up

Opdivo remains the only PD-1 inhibitor to demonstrate
statistically significant OS versus standard chemotherapy in the primary
analysis of a Phase 3 trial in these patients, with benefit maintained
with long-term follow-up

PRINCETON, N.J.–(BUSINESS WIRE)–$BMY #AACR18Bristol-Myers
Squibb Company
(NYSE: BMY) announced today two-year overall survival
(OS) data from CheckMate -141, a Phase 3 open-label, randomized trial
evaluating Opdivo (nivolumab) compared with investigator’s choice
chemotherapy (cetuximab, docetaxel or methotrexate) in patients with
recurrent or metastatic squamous cell carcinoma of the head and neck
(SCCHN) after failure on platinum-based therapy. Patients treated with Opdivo
experienced a 32% reduction in the risk of death after a minimum two
years of follow-up (HR 0.68; 95% CI: 0.54 to 0.86), with a median OS of
7.7 months (95% CI: 5.7 to 8.8) compared with 5.1 months (95% CI: 4.0 to
6.2) for standard chemotherapy. The two-year survival rate for Opdivo was
16.9% (95% CI: 12.4 to 22.0) versus 6.0% (95% CI: 2.7 to 11.3) for
standard chemotherapy. The safety profile for Opdivo at two-year
follow-up was consistent with previous analyses from the study.

These data will be presented today as an oral presentation (Abstract
#CT116) at 4:35 PM CDT, N Hall C (Level 1) during the Updates in
Immuno-Oncology Trials session at the 2018 American Association for
Cancer Research (AACR) Annual Meeting in Chicago.

“The introduction of Immuno-Oncology has the potential to change the
treatment landscape of squamous cell carcinoma of the head and neck,
compared with the standard of care,” said Robert L. Ferris, M.D., Ph.D.,
a cancer immunotherapist and Director, UPMC Hillman Cancer Center,
Pittsburgh, PA. “The sustained overall survival benefit demonstrated by
nivolumab in this study is encouraging in SCCHN, which historically has
a median survival of less than six months.”

The sustained Opdivo OS benefit was observed across PD-L1
expressors and non-expressors in patients with recurrent or
metastatic SCCHN. At the two-year follow-up in patients treated with Opdivo
whose tumors had PD-L1 expression ≥ 1%, risk of death was reduced by 45%
(HR 0.55; 95% CI: 0.39 to 0.78). For patients treated with Opdivo whose
tumors had PD-L1 expression <1%, risk of death at two years was reduced by 27% (HR 0.73; 95% CI: 0.49 to 1.09) versus standard chemotherapy.

Opdivo is the only I-O treatment for squamous cell carcinoma of
the head and neck to have shown a significant overall survival benefit
versus chemotherapy at the primary analysis. These two-year follow-up
data show a sustained long-term overall survival benefit for patients,
across PD-L1 expression levels and regardless of HPV status,” said
Shinta Cheng, M.D., Ph.D., development lead, Bristol-Myers Squibb.
“These data showing the durability of this benefit reinforce our ongoing
commitment to continuing research with the hope of delivering what
matters most to patients fighting cancer: long-term survival.”

There were no statistically significant differences between the two arms
for PFS (HR 0.87; 95% CI: 0.68 to 1.11) for Opdivo and
investigator’s choice, respectively. The safety profile of Opdivo
with a two-year follow-up was consistent with previous analyses
and with prior studies of Opdivo in patients with melanoma and
non-small cell lung cancer. Grade 3-4 treatment-related adverse
reactions occurred in 15.3% of patients receiving Opdivo
versus 36.9% of patients receiving investigator’s choice.

About CheckMate -141 (Abstract #CT116)

CheckMate -141 is a global phase 3, open-label, randomized trial
evaluating Opdivo versus investigator’s choice chemotherapy in
patients with recurrent or metastatic SCCHN who had tumor progression
during or within six months of receiving platinum-based therapy
administered in the adjuvant, neo-adjuvant, primary (unresectable
locally advanced) or metastatic setting. Patients were included
regardless of their HPV or PD-L1 status. Patients were randomized 2:1 to
receive Opdivo 3 mg/kg intravenously over 60 minutes every
two weeks (n=240), or investigator’s choice (n=121) of methotrexate 40
to 60 mg/m2 intravenously weekly, docetaxel 30 to 40 mg/m2
intravenously weekly, or cetuximab 400 mg/m2 intravenously
once then 250 mg/mweekly. The primary endpoint is
OS. The trial’s secondary endpoints include progression-free survival
(PFS) and objective response rate (ORR).

About Head & Neck Cancer

Cancers that are known as head and neck cancers usually begin in the
squamous cells that line the moist mucosal surfaces inside the head and
neck, such as inside the mouth, the nose and the throat. Head and neck
cancer is the seventh most common cancer globally, with an estimated
400,000 to 600,000 new cases per year and 223,000 to 300,000 deaths per
year. The five-year survival rate is reported as less than 4% for
metastatic Stage IV disease. Squamous cell carcinoma of the head and
neck (SCCHN) accounts for approximately 90% of all head and neck
cancers, with global incidence expected to increase by 17% between 2012
and 2022. Risk factors for SCCHN include tobacco and alcohol
consumption. The human papillomavirus (HPV) infection is also a risk
factor leading to rapid increase in oropharyngeal SCCHN in Europe and
North America. Quality of life is often impacted for SCCHN patients, as
physiological function (breathing, swallowing, eating, drinking),
personal characteristics (appearance, speaking, voice), sensory function
(smell and hearing), and psychological/social function can be affected.

Bristol-Myers Squibb & Immuno-Oncology:
Advancing Oncology Research

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 for
hard-to-treat cancers that could potentially improve outcomes for these
patients.

We are advancing the scientific understanding of I-O through our
extensive portfolio of investigational compounds and approved agents.
Our differentiated clinical development program is studying broad
patient populations across more than 50 types of cancers with 24
clinical-stage molecules designed to target different immune system
pathways. Our deep expertise and innovative clinical trial designs
position us to advance I-O/I-O, I-O/chemotherapy, I-O/targeted therapies
and I-O/radiation therapies across multiple tumors and potentially
deliver the next wave of therapies with a sense of urgency. Through our
leading translational capabilities, we are pioneering immune biology
research and identifying a number of potentially predictive biomarkers,
including PD-L1, TMB, MSI-H/dMMR and LAG-3, advancing the possibility of
precision medicine for more patients with cancer.

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), in combination with YERVOY®
(ipilimumab), is indicated for the treatment of patients with
intermediate or poor-risk, previously untreated advanced renal cell
carcinoma (RCC).

OPDIVO® (nivolumab) is indicated for the treatment of adult
patients with classical Hodgkin lymphoma (cHL) that has relapsed or
progressed after autologous hematopoietic stem cell transplantation
(HSCT) and brentuximab vedotin or after 3 or more lines of systemic
therapy that includes autologous HSCT. 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.

OPDIVO® (nivolumab) is indicated for the treatment of
patients with locally advanced or metastatic urothelial carcinoma who
have disease progression during or following platinum-containing
chemotherapy or have disease progression within 12 months of neoadjuvant
or adjuvant treatment with platinum-containing chemotherapy. This
indication is approved under accelerated approval based on tumor
response rate and duration of response. 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 adult
and pediatric (12 years and older) patients with microsatellite
instability high (MSI-H) or mismatch repair deficient (dMMR) metastatic
colorectal cancer (CRC) that has progressed following treatment with a
fluoropyrimidine, oxaliplatin, and irinotecan. This indication is
approved under accelerated approval based on overall response rate and
duration of response. 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 hepatocellular carcinoma (HCC) who have been previously
treated with sorafenib. 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.

OPDIVO® (nivolumab) is indicated for the adjuvant treatment
of patients with melanoma with involvement of lymph nodes or metastatic
disease who have undergone complete resection.

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 1 mg/kg with YERVOY 3 mg/kg, immune-mediated
pneumonitis occurred in 6% (25/407) of patients. In patients receiving
OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated pneumonitis occurred
in 4.4% (24/547) of patients.

In Checkmate 205 and 039, pneumonitis, including interstitial lung
disease, occurred in 6.0% (16/266) of patients receiving OPDIVO.
Immune-mediated pneumonitis occurred in 4.9% (13/266) of patients
receiving OPDIVO: Grade 3 (n=1) and Grade 2 (n=12).

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 1 mg/kg with YERVOY 3 mg/kg,
immune-mediated colitis occurred in 26% (107/407) of patients including
three fatal cases. In patients receiving OPDIVO 3 mg/kg with YERVOY 1
mg/kg, immune-mediated colitis occurred in 10% (52/547) of patients.

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. For patients without HCC, withhold OPDIVO for Grade 2 and
permanently discontinue OPDIVO for Grade 3 or 4. For patients with HCC,
withhold OPDIVO and administer corticosteroids if AST/ALT is within
normal limits at baseline and increases to >3 and up to 5 times the
upper limit of normal (ULN), if AST/ALT is >1 and up to 3 times ULN at
baseline and increases to >5 and up to 10 times the ULN, and if AST/ALT
is >3 and up to 5 times ULN at baseline and increases to >8 and up to 10
times the ULN. Permanently discontinue OPDIVO and administer
corticosteroids if AST or ALT increases to >10 times the ULN or total
bilirubin increases >3 times the ULN. In patients receiving OPDIVO
monotherapy, immune-mediated hepatitis occurred in 1.8% (35/1994) of
patients. In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg,
immune-mediated hepatitis occurred in 13% (51/407) of patients. In
patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated
hepatitis occurred in 7% (38/547) of patients.

In Checkmate 040, immune-mediated hepatitis requiring systemic
corticosteroids occurred in 5% (8/154) of patients receiving OPDIVO.

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 1 mg/kg with YERVOY
3 mg/kg, hypophysitis occurred in 9% (36/407) of patients. In patients
receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, hypophysitis occurred in
4.6% (25/547) of patients In patients receiving OPDIVO monotherapy,
adrenal insufficiency occurred in 1% (20/1994) of patients. In patients
receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg, adrenal insufficiency
occurred in 5% (21/407) of patients. In patients receiving OPDIVO 3
mg/kg with YERVOY 1 mg/kg, adrenal insufficiency occurred in 7% (41/547)
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 1 mg/kg with
YERVOY 3 mg/kg, hypothyroidism or thyroiditis resulting in
hypothyroidism occurred in 22% (89/407) of patients. Hyperthyroidism
occurred in 8% (34/407) of patients receiving this dose of OPDIVO with
YERVOY. In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg,
hypothyroidism or thyroiditis resulting in hypothyroidism occurred in
22% (119/547) of patients. Hyperthyroidism occurred in 12% (66/547) of
patients receiving this dose of OPDIVO with YERVOY. In patients
receiving OPDIVO monotherapy, diabetes occurred in 0.9% (17/1994) of
patients. In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg,
diabetes occurred in 1.5% (6/407) of patients. In patients receiving
OPDIVO 3 mg/kg with YERVOY 1 mg/kg, diabetes occurred in 2.7% (15/547)
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 1 mg/kg with YERVOY
3 mg/kg, immune-mediated nephritis and renal dysfunction occurred in
2.2% (9/407) of patients. In patients receiving OPDIVO 3 mg/kg with
YERVOY 1 mg/kg, immune-mediated nephritis and renal dysfunction occurred
in 4.6% (25/547) 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 1 mg/kg with YERVOY 3 mg/kg, immune-mediated rash
occurred in 22.6% (92/407) of patients. In patients receiving OPDIVO 3
mg/kg with YERVOY 1 mg/kg, immune-mediated rash occurred in 16.6%
(91/547) 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.

Contacts

Bristol-Myers Squibb
Media:
Audrey Abernathy,
919-605-4521
audrey.abernathy@bms.com
or
Investor:
Tim
Power, 609-252-7509
timothy.power@bms.com
Bill
Szablewski, 609-252-5894
william.szablewski@bms.com

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