Objective response rate (ORR) was 24% in 29
evaluable patients and increased in inflamed (PD-L1 positive)
tumors, with ORR of 41% in patients with ≥1% PD-L1
expression
No significant added toxicity over
Opdivo monotherapy observed
First disclosure of data for clinical
activity with the combination of anti-KIR and anti-PD-1 therapy
will include results for diverse biomarker subgroups
Bristol-Myers Squibb Company (NYSE:BMY) and Innate Pharma SA
(Euronext Paris: FR0010331421 – IPH) today announced an interim
efficacy analysis from a Phase 1/2 study of the combination of
lirilumab and Opdivo (nivolumab) in the cohort of advanced platinum
refractory squamous cell carcinoma of the head and neck (SCCHN),
including exploratory biomarker analyses of patient response by
level of PD-L1 expression. Among 29 evaluable patients with SCCHN,
the objective response rate (ORR), a secondary endpoint measured by
Response Evaluation Criteria In Solid Tumors (RECIST), was 24%
(n=7). Seventeen percent (n=5) of these evaluable patients had deep
responses, with reductions in tumor burden greater than 80%. Early
signals of enhanced clinical benefit were observed in PD-L1
positive tumors, with an ORR of 41% (7/17) in patients with ≥1%
PD-L1 expression.
Lirilumab is directed against the inhibitory killer-cell
immunoglobulin-like receptors (KIRs) expressed predominantly on
natural killer (NK) cells, which belong to the innate immune
system, while Opdivo blocks the inhibitory function of the PD-1
receptor on T cells. These data mark the first report of potential
efficacy with an anti-KIR antibody in combination with an anti-PD-1
therapy, and were presented at a late-breaking oral presentation
(abstract 456) at the Society for Immunotherapy of Cancer (SITC) 31
Annual Meeting on November 12 at 11:15 a.m. EST in National Harbor,
Maryland. Preliminary efficacy and exploratory biomarker analyses
of patient response by biomarker subgroups were presented.
The safety profile associated with lirilumab in combination with
Opdivo was generally consistent with that observed with Opdivo
monotherapy. The overall rate of treatment-related adverse events
(TRAEs) was reported as 72% (114/159) and the rate of Grade 3-4
TRAEs was 15% (24/159). Discontinuations due to TRAEs occurred in
8% of patients (12/159). These safety data were also reported at
the 2016 European Society for Medical Oncology (ESMO) Congress.
“The interim efficacy results indicate that targeting both the
KIR and PD-1 pathways with lirilumab and Opdivo, respectively, may
provide enhanced clinical activity, particularly in PD-L1 positive
tumors, with deep and durable responses in some patients," said Rom
Leidner, Medical Oncologist, Earle A. Chiles Research Institute,
Providence Cancer Center, and lead author of the study. "We look
forward to continuing the study of this novel combination in
patients with advanced platinum refractory squamous cell carcinoma
of the head and neck, which is the seventh-leading cause of cancer
globally.”
“The preliminary signals of anti-tumor activity we are seeing
with the combination of lirilumab and Opdivo in head and neck
cancer patients compare favorably to data previously presented on
Opdivo monotherapy in a similar patient population. We are
encouraged by the suggestion of enhanced benefit, particularly in
inflamed tumors as defined by increasing PD-L1 expression," said
Tim Reilly, head of Oncology Early Assets Development at
Bristol-Myers Squibb. "We aim to apply what we have been learning
about these complementary mechanisms and biomarker subgroups to
maximize the potential clinical benefit of lirilumab and Opdivo
across a range of tumor types and are excited about continuing to
expand our study of Opdivo with complementary pathways.”
“We are very encouraged by these interim efficacy data and are
eagerly awaiting the next steps of the clinical development of the
combination of lirilumab and Opdivo” said Pierre Dodion, Chief
Medical Officer of Innate Pharma. “These clinical data constitute
crucial progress that validates our pioneering work on the role of
innate immunity and NK cells in cancer. They support our ambition
to be at the forefront of developing novel combination
immunotherapies.”
About CA223-001: A Phase 1/2 Dose Escalation and Cohort
Expansion Study of the Safety, Tolerability and Efficacy of
Anti-KIR (Lirilumab) Administered in Combination With Anti-PD-1
(Nivolumab) in Advanced Refractory Solid Tumors
CA223-001 is a Phase 1/2 dose escalation and cohort expansion
study of lirilumab in combination with nivolumab in 159 patients
with advanced solid tumors. In this trial, patients received
lirilumab (0.1, 0.3, 1.0, or 3.0 mg/kg) once every 4 weeks and
nivolumab (3 mg/kg) once every 2 weeks.
During dose escalation, patients with advanced solid tumors who
progressed after ≥ 1 prior therapy received lirilumab 0.1–3.0 mg/kg
once every 4 weeks (Q4W) plus nivolumab 3.0 mg/kg Q2W. Cohort
expansion was initiated at the maximum dose of lirilumab 3.0 mg/kg
Q4W plus nivolumab 3.0 mg/kg Q2W in patients with advanced solid
tumors. The data reported at SITC pertain to an expansion cohort in
SCCHN. Key study endpoints include safety (primary), objective
response rate (ORR), disease control rate (DCR), duration of
response (DOR), and biomarker assessments.
The purpose of this Phase 1/2 open label study is to determine
the safety of the combination of lirilumab and nivolumab and to
explore the preliminary anti-tumor activity of the combination in
patients with a range of advanced solid tumors.
About Lirilumab (IPH2102/BMS-986015):
Lirilumab is a fully human monoclonal antibody that is designed
to act as a checkpoint inhibitor by blocking the interaction
between KIR2DL-1,-2,-3 inhibitory receptors and their ligands.
Blocking these receptors facilitates activation of NK cells and
potentially some subsets of T cells, ultimately leading to
destruction of tumor cells.
Lirilumab is licensed to Bristol-Myers Squibb Company. As part
of the agreement with Innate Pharma, Bristol-Myers Squibb holds
exclusive worldwide rights to develop, manufacture and
commercialize lirilumab and related compounds blocking KIR
receptors, for all indications. Under the agreement, Innate Pharma
conducts the development of lirilumab through Phase 2 in acute
myeloid leukemia (“AML”).
Innate Pharma is currently testing lirilumab in a randomized,
double-blind, placebo-controlled Phase 2 trial as maintenance
treatment in elderly patients with AML in first complete remission
(“EffiKIR” trial). In addition, lirilumab is also being evaluated
by Bristol-Myers Squibb in clinical trials in combination with
other agents in a variety of tumor types.
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 Papilloma Virus
(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 (taste, smell,
hearing), and psychological/social function can be affected.
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 57 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 47 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 for OPDIVO and
YERVOY, including Boxed WARNING regarding immune-mediated
adverse reactions for YERVOY.
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
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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 12 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.
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, Yervoy or any of the compounds mentioned in this
release will receive regulatory approval for an initial or
additional indication. 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.
About Innate Pharma
Innate Pharma S.A. is a clinical-stage biotechnology company
with a focus on discovering and developing first-in-class
therapeutic antibodies that harness the innate immune system to
improve cancer treatment and clinical outcomes for patients.
Innate Pharma specializes in immuno-oncology, a new therapeutic
field that is changing cancer treatment by mobilizing the power of
the body’s immune system to recognize and kill cancer cells.
The Company’s aim is to become a commercial stage
biopharmaceutical company in the area of immunotherapy and focused
on serious unmet medical needs in cancer. Innate Pharma has
pioneered the discovery and development of checkpoint inhibitors to
activate the innate immune system. Innate Pharma's innovative
approach has resulted in three first-in-class, clinical-stage
antibodies targeting natural killer cell receptors that may address
a broad range of solid and hematological cancer indications as well
as additional preclinical product candidates and technologies.
Targeting receptors involved in innate immunity also creates
opportunities for the Company to develop therapies for inflammatory
diseases.
The Company's expertise and understanding of natural killer cell
biology have enabled it to enter into major alliances with leaders
in the biopharmaceutical industry including AstraZeneca,
Bristol-Myers Squibb, Novo Nordisk A/S and Sanofi.
Based in Marseille, France, Innate Pharma has more than 140
employees and is listed on Euronext Paris. Learn more about Innate
Pharma at www.innate-pharma.com.
About Innate Pharma shares:
ISIN code FR0010331421 Ticker code IPH
Innate Pharma Forward-Looking Statements:
This press release contains certain forward-looking statements.
Although the company believes its expectations are based on
reasonable assumptions, these forward-looking statements are
subject to numerous risks and uncertainties, which could cause
actual results to differ materially from those anticipated. For a
discussion of risks and uncertainties which could cause the
company's actual results, financial condition, performance or
achievements to differ from those contained in the forward-looking
statements, please refer to the Risk Factors (“Facteurs de Risque")
section of the Document de Reference prospectus filed with the AMF,
which is available on the AMF website (http://www.amf-france.org)
or on Innate Pharma’s website.
This press release and the information contained herein do not
constitute an offer to sell or a solicitation of an offer to buy or
subscribe to shares in Innate Pharma in any country.
View source
version on businesswire.com: http://www.businesswire.com/news/home/20161112005007/en/
Bristol-Myers SquibbInvestors:Tim Power,
609-252-7509timothy.power@bms.comorBill Szablewski,
609-252-5894william.szablewski@bms.comorMedia:Sarah Koenig,
609-252-4145sarah.koenig@bms.comorInnate
PharmaInvestors:Laure-Hélène Mercier, +33 (0)4 30 30 30
87investors@innate-pharma.comorMedia:ATCG Press (France),
Marie Puvieux, +33 (0)6 10 54 36
72presse@atcg-partners.comorConsilium Strategic Communications
(ROW), Mary-Jane Elliott / Sue Stuart /Jessica Hodgson / Hendrik
Thys, +44 (0)20 3709 5700InnatePharma@consilium-comms.com
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