Advaxis, Inc. (NASDAQ:ADXS) and Bristol-Myers Squibb (NYSE:BMY)
today announced a clinical development collaboration to evaluate
ADXS-DUAL, an investigational immunotherapy targeting
HPV-associated cancers, and Bristol-Myers Squibb’s PD-1 immune
checkpoint inhibitor, Opdivo (nivolumab), as a potential
combination treatment option for women with metastatic cervical
cancer.
Expected to start by the end of this year, the study will
evaluate this combination regimen in women with persistent,
recurrent or metastatic (squamous or non-squamous cell) carcinoma
of the cervix who have failed at least one prior line of systemic
chemotherapy. Under the terms of the agreement, each party will
bear their own internal costs and provide its immunotherapy agents.
Advaxis will sponsor the study and pay third-party costs.
Advaxis developed ADXS-DUAL by building on the learnings from
the clinical development of axalimogene filolisbac and has
incorporated additional HPV target antigens into its Listeria
monocytogenes (Lm) bacterial vector.
“The additional HPV antigens have the potential to provide
coverage against numerous HPV types in cervical cancer and other
HPV-associated cancers,” said Daniel J. O’Connor, President and
Chief Executive Officer of Advaxis. “By studying the combination of
Opdivo and ADXS-DUAL, we hope to bring a new option to metastatic
cervical cancer patients with persistent, recurrent or metastatic
disease. We are looking forward to working with Bristol-Myers
Squibb to explore the potential of this combination.”
Opdivo was the first PD-1 immune checkpoint inhibitor to receive
regulatory approval anywhere in the world in July 2014, and
currently has regulatory approval in 57 countries including the
United States, Japan and in the European Union.
“Combining immunotherapy agents is at the core of
Bristol-Myers Squibb’s strategy, as it brings the opportunity to
improve anti-tumor efficacy,” said Fouad Namouni, M.D. head
of Oncology Development at Bristol-Myers Squibb. “We are
excited to work with Advaxis to explore the potential
of Opdivo and ADXS-DUAL to provide
a potential new option for metastatic cervical
cancer patients where there is a high unmet need.”
About Cervical Cancer
Cervical cancer is the fourth most common cancer affecting women
worldwide. An estimated 13,000 cases were diagnosed in the United
States in 2016, and 4,100 women will have this disease as their
cause of death each year, according to the National Cancer
Institute. Decades of research have shown that persistent HPV
infection, particularly with high-risk virus types such as HPV-16
and HPV-18, is the most important factor in the development of
cervical cancer. The prognosis for women with advanced and
recurrent cervical cancer remains poor, with median survival of
only six to seven months following initiation of palliative
treatment with chemotherapy. According to the American Cancer
Society, the five-year survival rate for Stage IV disease is at 15
to 16 percent. There is no approved therapy following failure of
first-line treatment, and there has been limited advancement in
developing new therapeutics for advanced cervical cancer over the
last 30 years.
About ADXS-DUAL
ADXS-DUAL, an investigational agent, is the next generation of
Advaxis’ immunotherapy targeting HPV-associated cancers.
Axalimogene filolisbac, which is being evaluated as a monotherapy
for patients with high-risk locally advanced cervical cancer in the
global Phase 3 AIM2CERV trial, is an irreversibly attenuated
Listeria monocytogenes-listeriolysin O immunotherapy bioengineered
to secrete an HPV-E7 protein fused with a truncated fragment of
listeriolysin O (tLLO). Studies have shown that it targets
HPV-transformed cells, inducing antitumor T-cell immunity and
breaking immune tolerance in the tumor microenvironment. ADXS-DUAL,
the second generation of axalimogene filolisbac, is an Lm-based
immunotherapy that secretes a fusion protein containing E7 protein
antigens from both major families of HPV.
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 leading 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
14 clinical-stage molecules designed to target different immune
system pathways. Our deep expertise and innovative clinical trial
designs position us to advance the 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. We also continue to pioneer research that will
help facilitate a deeper understanding of the role of immune
biomarkers and how a patient’s tumor biology can be used as a guide
for treatment decisions throughout their journey.
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 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.
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 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 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, adverse reactions
leading to discontinuation occurred in 7% and dose delays due
to adverse reactions occurred in 34% of patients
(n=266). Serious adverse reactions occurred in 26% of
patients. The most frequent serious adverse reactions reported
in ≥1% of patients were pneumonia, infusion-related reaction,
pyrexia, colitis or diarrhea, pleural effusion, pneumonitis,
and rash. Eleven patients died from causes other than
disease progression: 3 from adverse reactions within 30 days
of the last OPDIVO dose, 2 from infection 8 to 9 months after
completing OPDIVO, and 6 from complications of allogeneic
HSCT. 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 infection, and sepsis. In Checkmate 275, serious adverse
reactions occurred in 54% of patients receiving OPDIVO (n=270). The
most frequent serious adverse reactions reported in at least 2% of
patients receiving OPDIVO were urinary tract infection, sepsis,
diarrhea, small intestine obstruction, and general physical health
deterioration.
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, the most
common adverse reactions (≥20%) reported in patients receiving
OPDIVO (n=266) were upper respiratory tract infection
(44%), fatigue (39%), cough (36%), diarrhea
(33%), pyrexia (29%), musculoskeletal pain (26%), rash
(24%), nausea (20%) and pruritus (20%). 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 Checkmate 275, the most common adverse reactions (≥
20%) reported in patients receiving OPDIVO (n=270) were fatigue
(46%), musculoskeletal pain (30%), nausea (22%), and decreased
appetite (22%).
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%).
Please see U.S. Full Prescribing Information
for OPDIVO and YERVOY, including Boxed
WARNING regarding immune-mediated adverse reactions for
YERVOY.
About Advaxis, Inc.
Located in Princeton, N.J., Advaxis, Inc. is a biotechnology
company developing multiple cancer immunotherapies based on its
proprietary Lm Technology™. The Lm Technology, using
bioengineered live attenuated Listeria monocytogenes (Lm)
bacteria, is the only known cancer immunotherapy agent shown in
preclinical studies to both generate cancer fighting T cells
directed against cancer antigens and neutralize Tregs and
myeloid-derived suppressor cells (MDSCs) that protect the tumor
microenvironment from immunologic attack and contribute to tumor
growth. Advaxis' lead Lm Technology immunotherapy,
axalimogene filolisbac, is designed to target HPV-associated
cancers and is in clinical trials for three potential indications:
Phase 3 in invasive cervical cancer, Phase 2 in head and neck
cancer, and Phase 2 in anal cancer. The FDA has granted axalimogene
filolisbac orphan drug designation for each of these three clinical
settings, as well as Fast Track designation for adjuvant therapy
for HRLACC patients and a SPA for the Phase 3 AIM2CERV trial in
high-risk, locally advanced cervical cancer patients. Axalimogene
filolisbac has also been classified as an advanced therapy
medicinal product for the treatment of cervical cancer by the EMA’s
CAT. Advaxis has two additional immunotherapy products: ADXS-PSA in
prostate cancer and ADXS-HER2 in HER2 expressing solid tumors, in
human clinical development. In addition, Advaxis and Amgen are
developing ADXS-NEO, a preclinical investigational cancer
immunotherapy treatment designed to activate a patient's immune
system to respond against the unique mutations, or neoepitopes,
contained in and identified from each individual patient's tumor,
with plans to enter the clinic in 2017.
To learn more about Advaxis, visit www.advaxis.com and connect
on Twitter, LinkedIn, Facebook, and YouTube.
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.
About the Bristol-Myers Squibb and Ono Pharmaceutical Co.,
Ltd. Collaboration
In 2011, through a collaboration agreement with Ono
Pharmaceutical Co., Ltd (Ono), Bristol-Myers Squibb expanded its
territorial rights to develop and commercialize Opdivo globally
except in Japan, South Korea and Taiwan, where Ono had retained all
rights to the compound at the time. On July 23, 2014, Bristol-Myers
Squibb and Ono 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.
Advaxis Forward-Looking Statement
This press release contains forward-looking statements,
including, but not limited to, statements regarding Advaxis’
ability to develop the next generation of cancer immunotherapies,
and the safety and efficacy of Advaxis’ proprietary immunotherapy,
axalimogene filolisbac. These forward-looking statements are
subject to a number of risks including the risk factors set forth
from time to time in Advaxis’ SEC filings including, but not
limited to, its report on Form 10-K for the fiscal year ended
October 31, 2016, which is available at http://www.sec.gov.
Any forward-looking statements set forth in this presentation
speak only as of the date of this presentation. We do not intend to
update any of these forward-looking statements to reflect events or
circumstances that occur after the date hereof other than as
required by law.
You are cautioned not to place undue reliance on any
forward-looking statements.
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 ADXS-DUAL in combination with Opdivo, will be
successfully developed or approved for any of the indications
described in this release. 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, 2016 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.
View source
version on businesswire.com: http://www.businesswire.com/news/home/20170530005179/en/
Advaxis, Inc.Ranya Dajani, 609-250-7559Vice President, Business
Developmentdajani@advaxis.comorMedia:JPA Health CommunicationsDavid
Connolly, 617-945-9316dconnolly@jpa.comorBristol-Myers
Squibb:Media:Lisa McCormick Lavery,
609-252-7602lisa.mccormicklavery@bms.comorKen Dominski,
609-252-5251ken.dominski@bms.comorInvestors:Tim Power,
609-252-7509timothy.power@bms.comorBill Szablewski,
609-252-5894william.szablewski@bms.com
Ayala Pharmaceuticals (CE) (USOTC:ADXS)
Historical Stock Chart
From Aug 2024 to Sep 2024
Ayala Pharmaceuticals (CE) (USOTC:ADXS)
Historical Stock Chart
From Sep 2023 to Sep 2024