- Evaluation of IPI-549 as a monotherapy continuing, with combination portion of Phase 1 study expected to begin this fall
- Study to evaluate potential of IPI-549 plus Opdivo to target immune-suppressive cells in the tumor microenvironment
Bristol-Myers
Squibb Company (NYSE: BMY) and Infinity
Pharmaceuticals, Inc. (NASDAQ: INFI) today announced a clinical
trial collaboration to evaluate Bristol-Myers Squibb’s
Opdivo
in combination with Infinity’s IPI-549 in patients with advanced solid
tumors. The dose-escalation portion exploring IPI-549 as a monotherapy
in Infinity’s Phase 1 study is continuing, and the first dose-escalation
cohort studying IPI-549 in combination with Opdivo, a PD-1 immune
checkpoint inhibitor, is expected to begin this fall. IPI-549 is
an oral immuno-oncology development candidate that is designed to
selectively inhibit phosphoinositide-3-kinase (PI3K)-gamma and is the
only investigational PI3K-gamma inhibitor in clinical development.
Preclinical data suggest that IPI-549 may enhance the effects of
checkpoint inhibitors and may also reverse tumor resistance to
checkpoint inhibitors by targeting immune cells and altering the
immune-suppressive microenvironment, promoting an anti-tumor immune
response. Opdivo is designed to overcome immune suppression. The
combination phase of this ongoing Phase 1 study in patients with
advanced solid tumors will explore the potential of combining these two
agents to drive improved and sustained efficacy and tolerability above
the current standard of care by targeting the immune-suppressive cells
in the tumor microenvironment.
“Targeting the tumor microenvironment is an important part of our
Immuno-Oncology strategy as we continue to advance research for cancers
with limited treatment options,” stated Fouad Namouni, M.D., Head of
Oncology Development, Bristol-Myers Squibb. “Our agreement with Infinity
builds on our continued focus to bring forward potential novel
combination treatment options for patients with cancer.”
“We are excited to explore the potential clinical benefits of combining
IPI-549 with Opdivo in the next phase of our ongoing Phase 1
study, which is expected to begin this fall,” stated Julian Adams,
president of research and development at Infinity. “Our preclinical
research demonstrates that IPI-549 may enhance the effects of and
reverse tumor resistance to checkpoint inhibitors, providing a strong
rationale for evaluating this combination in patients with advanced
forms of solid tumors.”
The ongoing Phase 1 clinical study of IPI-549 is designed to explore the
activity, safety, tolerability, pharmacokinetics and pharmacodynamics of
IPI-549 as a monotherapy and in combination with Opdivo in
approximately 175 patients with advanced solid tumors. Once the
dose-escalation phase evaluating Opdivo plus IPI-549 is
completed, an expansion phase is planned to evaluate the combination in
patients with selected solid tumors, including non-small cell lung
cancer (NSCLC), melanoma and squamous cell carcinoma of the head and
neck (SCCHN).
Although there has been great progress in the treatment of cancer, there
remains a need for additional treatment options. NSCLC, melanoma and
SCCHN, which will comprise three of the expansion cohorts in this Phase
1 study, account for more than 17 percent of all new cancer cases in the
U.S.
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 54 countries including the United
States, Japan, and in the European Union.
About IPI-549
IPI-549 is an investigational, orally administered immuno-oncology
development candidate that is designed to selectively inhibit
PI3K-gamma. In preclinical studies, IPI-549 inhibited immune suppressive
macrophages within the tumor microenvironment, whereas other
immunotherapies such as checkpoint modulators more directly target
immune effector cell function. As such, IPI-549 represents a potentially
complementary approach to restoring anti-tumor immunity in combination
with other immunotherapies such as checkpoint inhibitors. IPI-549 is an
investigational compound and its safety and efficacy has not been
evaluated by the U.S. Food and Drug Administration or any other health
authority.
Bristol-Myers Squibb & Immuno-Oncology:
Advancing Oncology Research
At Bristol-Myers Squibb, we have a vision for the future of cancer care
that is focused on Immuno-Oncology, now considered a major treatment
choice alongside surgery, radiation, chemotherapy and targeted therapies
for certain types of cancer.
We have a comprehensive clinical portfolio of investigational and
approved Immuno-Oncology agents, many of which were discovered and
developed by our scientists. Our ongoing Immuno-Oncology clinical
program is looking at broad patient populations, across multiple solid
tumors and hematologic malignancies, and lines of therapy and
histologies, with the intent of powering our trials for overall survival
and other important measures like durability of response. We pioneered
the research leading to the first regulatory approval for the
combination of two Immuno-Oncology agents and continue to study the role
of combinations in cancer.
We are also investigating other immune system pathways in the treatment
of cancer including CTLA-4, CD-137, KIR, SLAMF7, PD-1, GITR, CSF1R, IDO
and LAG-3. These pathways may lead to potential new treatment options –
in combination or monotherapy – to help patients fight different types
of cancers.
Our collaboration with academia, as well as small and large biotech and
pharmaceutical companies, to research the potential of Immuno-Oncology
and non-Immuno-Oncology combinations helps achieve our goal of providing
new treatment options in clinical practice.
At Bristol-Myers Squibb, we are committed to changing survival
expectations in hard-to-treat cancers and the way patients live with
cancer.
About Opdivo
Cancer cells may exploit “regulatory” pathways, such as checkpoint
pathways, to hide from the immune system and shield the tumor from
immune attack. Opdivo is a PD-1 immune checkpoint inhibitor that
binds to the checkpoint receptor PD-1 expressed on activated T-cells,
and blocks the binding of PD-L1 and PD-L2, preventing the PD-1 pathway’s
suppressive signaling on the immune system, including the interference
with an anti-tumor immune response.
Opdivo’s broad global development program is based on
Bristol-Myers Squibb’s understanding of the biology behind
Immuno-Oncology. Our company is at the forefront of researching the
potential of Immuno-Oncology to extend survival in hard-to-treat
cancers. This scientific expertise serves as the basis for the Opdivo
development program, which includes a broad range of Phase 3 clinical
trials evaluating overall survival as the primary endpoint across a
variety of tumor types. The Opdivo trials have also contributed
toward the clinical and scientific understanding of the role of
biomarkers and how patients may benefit from Opdivo across the
continuum of PD-L1 expression. To date, the Opdivo clinical
development program has enrolled more than 18,000 patients.
U.S. INDICATIONS & IMPORTANT SAFETY INFORMATION
INDICATIONS
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.
Please refer to the end of the Important Safety Information for a
brief description of the patient populations studied in the Checkmate
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 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]).
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 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.
Please see U.S. Full Prescribing Information for OPDIVO
and YERVOY,
including Boxed WARNING regarding immune-mediated adverse reactions
for YERVOY.
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.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission
is to discover, develop and deliver innovative medicines that help
patients prevail over serious diseases. For more information about
Bristol-Myers Squibb, visit us at BMS.com or
follow us on LinkedIn, Twitter,
YouTube
and Facebook.
Bristol-Myers Squibb Forward-Looking Statement
This press release contains "forward-looking statements" as that term
is defined in the Private Securities Litigation Reform Act of 1995
regarding the research, development and commercialization of
pharmaceutical products. Such forward-looking statements are based on
current expectations and involve inherent risks and uncertainties,
including factors that could delay, divert or change any of them, and
could cause actual outcomes and results to differ materially from
current expectations. No forward-looking statement can be guaranteed.
Among other risks, there can be no guarantee that Opdivo in combination
with IPI-549, will receive regulatory approval for the treatment of
cancer. 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.
Infinity’s Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within the
meaning of The Private Securities Litigation Reform Act of 1995. Such
forward-looking statements include those regarding: the therapeutic
potential of PI3K-gamma selective inhibition and IPI-549, alone and in
combination with checkpoint inhibitors, including Opdivo; and clinical
trial plans regarding IPI-549. Such statements are subject to numerous
important factors, risks and uncertainties that may cause actual events
or results to differ materially from Infinity’s current expectations.
For example, there can be no guarantee that IPI-549 will successfully
complete necessary preclinical and clinical development phases, or that
development of any of Infinity’s product candidates will continue.
Management’s expectations and, therefore, any forward-looking statements
in this press release could also be affected by risks and uncertainties
relating to a number of other factors, including the following:
Infinity’s results of clinical trials and preclinical studies, including
subsequent analysis of existing data and new data received from ongoing
and future studies; the content and timing of decisions made by the
U.S. FDA and other regulatory authorities; Infinity’s ability to obtain
and maintain requisite regulatory approvals and to enroll patients in
its clinical trials; unplanned cash requirements and expenditures;
development of agents by Infinity’s competitors for diseases in which
Infinity is currently developing or intends to develop IPI-549; and
Infinity’s ability to obtain, maintain and enforce patent and other
intellectual property protection for any product candidates it is
developing. These and other risks which may impact management’s
expectations are described in greater detail under the caption “Risk
Factors” included in Infinity’s Annual Report on Form 10-K for the year
ended December 31, 2015, in our quarterly report on Form 10-Q, and other
filings filed by Infinity with the SEC. Any forward-looking statements
contained in this press release speak only as of the date hereof, and
Infinity expressly disclaims any obligation to update any
forward-looking statements, whether as a result of new information,
future events or otherwise.
Bristol-Myers Squibb Media: Lisa McCormick Lavery, 609-252-7602, lisa.mccormicklavery@bms.com Ken Dominski, 609-252-5251, ken.dominski@bms.com Investors: Tim Power, 609-252-7509, timothy.power@bms.com Bill Szablewski, 609-252-5894, william.szablewski@bms.com or Infinity Pharmaceuticals, Inc. Jaren MaddenSenior Director, Investor Relations and Corporate Communications617-453-1336 or Jaren.Madden@infi.com