-- Plans to Initiate MARIO-275, a Randomized,
Global Phase 2 Study in 1H’19--
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
urothelial cancer. 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.
Infinity will operationalize MARIO-275: MAcrophage Reprogramming in Immuno-Oncology, a
global, randomized Phase 2 study to evaluate the effect of adding
IPI-549 to Opdivo in checkpoint-naïve advanced urothelial cancer
patients who have progressed or recurred following treatment with
platinum-based chemotherapy. Approximately 150 patients will be
randomized between combination therapy and Opdivo monotherapy. The
primary endpoint of the trial will be overall response rate, which
will be assessed in the overall population as well as in subsets of
patients with different baseline levels of myeloid derived
suppressor cells (MDSCs). Opdivo is approved for use by the FDA as
a single agent in patients with locally advanced or metastatic
urothelial cancer who have progressed or recurred following
treatment with platinum-based chemotherapy or who have disease
progression within 12 months of neoadjuvant or adjuvant treatment
with platinum-containing chemotherapy. In exploratory analyses of
the CheckMate -275 data, high levels of MDSCs were associated with
shorter overall survival in patients treated with Opdivo2. In
Infinity’s MARIO-1 trial, MDSCs were reduced in the majority of
patients treated with IPI-549 monotherapy.3 IPI-549 in combination
with Opdivo has been administered to over 80 patients and
demonstrated early evidence of clinical activity with
translational studies demonstrating evidence of on-mechanism
IPI-549-mediated effects.4
"The expansion of our relationship with Infinity underscores our
efforts to follow the science and support potential novel
combination therapies in immuno-oncology for cancer patients with
limited treatment options," said Fouad Namouni, M.D., head of
Oncology Development, Bristol-Myers Squibb. "Our goal is to
determine whether targeting the tumor microenvironment with IPI-549
will enhance the activity of Opdivo for people with urothelial
cancer and potentially in other tumor types where MDSCs suppress
the immune response.”
"We are excited to advance the development of IPI-549 further
into the checkpoint inhibitor treatment-naïve setting with this
randomized study in collaboration with the team at Bristol-Myers
Squibb.,” said Dr. Sam Agresta, Chief Medical Officer of Infinity.
"There continues to be a significant unmet need for additional
treatment options for people living with urothelial cancer, and we
are excited to evaluate the potential of this combination.”
Infinity is continuing to evaluate IPI-549 in combination with
Opdivo in MARIO-1, a Phase 1/1b study in patients with advanced
solid tumors.
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 Opdivo
Opdivo is a programmed death-1 (PD-1) immune checkpoint
inhibitor that is designed to uniquely harness the body’s own
immune system to help restore anti-tumor immune response. By
harnessing the body’s own immune system to fight
cancer, Opdivo has become an important treatment option
across multiple cancers.
Opdivo’s leading global development program is based on
Bristol-Myers Squibb’s scientific expertise in the field of
Immuno-Oncology and includes a broad range of clinical trials
across all phases, including Phase 3, in a variety of tumor types.
To date, the Opdivo clinical development program has
enrolled more than 25,000 patients. The Opdivo trials
have contributed to gaining a deeper understanding of the potential
role of biomarkers in patient care, particularly regarding how
patients may benefit from Opdivo across the continuum of
PD-L1 expression.
In July 2014, Opdivo was the first PD-1 immune
checkpoint inhibitor to receive regulatory approval anywhere in the
world. Opdivo is currently approved in more than 60
countries, including the United States, the European Union, and
Japan. In October 2015, the
company’s Opdivo and Yervoy combination regimen was
the first Immuno-Oncology combination to receive regulatory
approval for the treatment of metastatic melanoma and is currently
approved in more than 50 countries, including the United States and
the European Union.
U.S. FDA-APPROVED INDICATIONS FOR
OPDIVO
OPDIVO® (nivolumab) as a single agent is indicated for the
treatment of patients with BRAF V600 mutation-positive unresectable
or metastatic melanoma. This indication is approved under
accelerated approval based on progression-free survival. Continued
approval for this indication may be contingent upon verification
and description of clinical benefit in the confirmatory trials.
OPDIVO® (nivolumab) as a single agent is indicated for the
treatment of patients with BRAF V600 wild-type unresectable or
metastatic melanoma.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab),
is indicated for the treatment of patients with unresectable or
metastatic melanoma. This indication is approved under accelerated
approval based on progression-free survival. Continued approval for
this indication may be contingent upon verification and description
of clinical benefit in the confirmatory trials.
OPDIVO® (nivolumab) is indicated for the treatment of patients
with metastatic non-small cell lung cancer (NSCLC) with progression
on or after platinum-based chemotherapy. Patients with EGFR or ALK
genomic tumor aberrations should have disease progression on
FDA-approved therapy for these aberrations prior to receiving
OPDIVO.
OPDIVO® (nivolumab) is indicated for the treatment of patients
with advanced renal cell carcinoma (RCC) who have received prior
anti-angiogenic therapy.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab),
is indicated for the treatment of patients with intermediate or
poor-risk, previously untreated advanced renal cell carcinoma
(RCC).
OPDIVO® (nivolumab) is indicated for the treatment of adult
patients with classical Hodgkin lymphoma (cHL) that has relapsed or
progressed after autologous hematopoietic stem cell transplantation
(HSCT) and brentuximab vedotin or after 3 or more lines of systemic
therapy that includes autologous HSCT. This indication is approved
under accelerated approval based on overall response rate.
Continued approval for this indication may be contingent upon
verification and description of clinical benefit in confirmatory
trials.
OPDIVO® (nivolumab) is indicated for the treatment of patients
with recurrent or metastatic squamous cell carcinoma of the head
and neck (SCCHN) with disease progression on or after
platinum-based therapy.
OPDIVO® (nivolumab) is indicated for the treatment of patients
with locally advanced or metastatic urothelial carcinoma who have
disease progression during or following platinum-containing
chemotherapy or have disease progression within 12 months of
neoadjuvant or adjuvant treatment with platinum-containing
chemotherapy. This indication is approved under accelerated
approval based on tumor response rate and duration of response.
Continued approval for this indication may be contingent upon
verification and description of clinical benefit in confirmatory
trials.
OPDIVO® (nivolumab) is indicated for the treatment of adult and
pediatric (12 years and older) patients with microsatellite
instability high (MSI-H) or mismatch repair deficient (dMMR)
metastatic colorectal cancer (CRC) that has progressed following
treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.
This indication is approved under accelerated approval based on
overall response rate and duration of response. Continued approval
for this indication may be contingent upon verification and
description of clinical benefit in confirmatory trials.
OPDIVO® (nivolumab) is indicated for the treatment of patients
with hepatocellular carcinoma (HCC) who have been previously
treated with sorafenib. This indication is approved under
accelerated approval based on tumor response rate and durability of
response. Continued approval for this indication may be contingent
upon verification and description of clinical benefit in the
confirmatory trials.
OPDIVO® (nivolumab) is indicated for the adjuvant treatment of
patients with melanoma with involvement of lymph nodes or
metastatic disease who have undergone complete resection.
IMPORTANT SAFETY INFORMATION
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 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. In patients
receiving OPDIVO monotherapy, immune-mediated colitis occurred in
2.9% (58/1994) of patients.
Immune-Mediated Hepatitis
OPDIVO can cause immune-mediated hepatitis. Monitor patients for
abnormal liver tests prior to and periodically during treatment.
Administer corticosteroids for Grade 2 or greater transaminase
elevations. For patients without HCC, withhold OPDIVO for Grade 2
and permanently discontinue OPDIVO for Grade 3 or 4. For patients
with HCC, withhold OPDIVO and administer corticosteroids if AST/ALT
is within normal limits at baseline and increases to >3 and up
to 5 times the upper limit of normal (ULN), if AST/ALT is >1 and
up to 3 times ULN at baseline and increases to >5 and up to 10
times the ULN, and if AST/ALT is >3 and up to 5 times ULN at
baseline and increases to >8 and up to 10 times the ULN.
Permanently discontinue OPDIVO and administer corticosteroids if
AST or ALT increases to >10 times the ULN or total bilirubin
increases >3 times the ULN. In patients receiving OPDIVO
monotherapy, immune-mediated hepatitis occurred in 1.8% (35/1994)
of patients.
In Checkmate 040, immune-mediated hepatitis requiring systemic
corticosteroids occurred in 5% (8/154) of patients receiving
OPDIVO.
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
monotherapy, adrenal insufficiency occurred in 1% (20/1994) 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 monotherapy, diabetes occurred in 0.9% (17/1994) of
patients.
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.
Immune-Mediated Skin Adverse Reactions
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.
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.
Other Immune-Mediated Adverse Reactions
Based on the severity of the adverse reaction, permanently
discontinue or withhold OPDIVO, administer high-dose
corticosteroids, and, if appropriate, initiate hormone-replacement
therapy. Across clinical trials of OPDIVO, the following clinically
significant immune-mediated adverse reactions, some with fatal
outcome, occurred in <1.0% of patients receiving OPDIVO:
myocarditis, rhabdomyolysis, myositis, uveitis, iritis,
pancreatitis, facial and abducens nerve paresis, demyelination,
polymyalgia rheumatica, autoimmune neuropathy, GuillainBarré
syndrome, hypopituitarism, systemic inflammatory response syndrome,
gastritis, duodenitis, sarcoidosis, histiocytic necrotizing
lymphadenitis (Kikuchi lymphadenitis), motor dysfunction,
vasculitis, aplastic anemia, pericarditis, and myasthenic
syndrome.
If uveitis occurs in combination with other immune-mediated
adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome,
which has been observed in patients receiving OPDIVO and may
require treatment with systemic steroids to reduce the risk of
permanent vision loss.
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 as a 60-minute infusion,
infusion-related reactions occurred in 6.4% (127/1994) of patients.
In a separate study in which patients received OPDIVO monotherapy
as a 60-minute infusion or a 30-minute infusion, infusion-related
reactions occurred in 2.2% (8/368) and 2.7% (10/369) of patients,
respectively. Additionally, 0.5% (2/368) and 1.4% (5/369) of
patients, respectively, experienced adverse reactions within 48
hours of infusion that led to dose delay, permanent discontinuation
or withholding of OPDIVO.
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 its mechanism of action, OPDIVO 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-containing regimen and for at least 5 months after the last
dose of OPDIVO.
Lactation
It is not known whether OPDIVO 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.
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 017 and 057, serious adverse
reactions occurred in 46% of patients receiving OPDIVO (n=418). The
most frequent serious adverse reactions reported in ≥2% of patients
receiving OPDIVO were pneumonia, pulmonary embolism, dyspnea,
pyrexia, pleural effusion, pneumonitis, and respiratory failure. In
Checkmate 032, serious adverse reactions occurred in 45% of
patients receiving OPDIVO (n=245). The most frequent serious
adverse reactions reported in at least 2% of patients receiving
OPDIVO were pneumonia, dyspnea, pneumonitis, pleural effusion, and
dehydration. 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 (n=236). The most frequent serious
adverse reactions reported in ≥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 ≥2% of patients
receiving OPDIVO were urinary tract infection, sepsis, diarrhea,
small intestine obstruction, and general physical health
deterioration. In Checkmate 040, serious adverse reactions occurred
in 49% of patients (n=154). The most frequent serious adverse
reactions reported in ≥2% of patients were pyrexia, ascites, back
pain, general physical health deterioration, abdominal pain, and
pneumonia. In Checkmate 238, Grade 3 or 4 adverse reactions
occurred in 25% of OPDIVO-treated patients (n=452). The most
frequent Grade 3 and 4 adverse reactions reported in ≥2% of
OPDIVO-treated patients were diarrhea and increased lipase and
amylase. Serious adverse reactions occurred in 18% of
OPDIVO-treated patients.
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 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 032, the
most common adverse reactions (≥20%) in patients receiving OPDIVO
(n=245) were fatigue (45%), decreased appetite (27%),
musculoskeletal pain (25%), dyspnea (22%), nausea (22%), diarrhea
(21%), constipation (20%), and cough (20%). In Checkmate 025, the
most common adverse reactions (≥20%) reported in patients receiving
OPDIVO (n=406) vs everolimus (n=397) were fatigue (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 (n=236) 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 Checkmate 142 in
MSI-H/dMMR mCRC patients receiving OPDIVO as a single agent, the
most common adverse reactions (≥20%) were fatigue (54%), diarrhea
(43%), abdominal pain (34%), nausea (34%), vomiting (28%),
musculoskeletal pain (28%), cough (26%), pyrexia (24%), rash (23%),
constipation (20%), and upper respiratory tract infection (20%). In
Checkmate 040, the most common adverse reactions (≥20%) in patients
receiving OPDIVO (n=154) were fatigue (38%), musculoskeletal pain
(36%), abdominal pain (34%), pruritus (27%), diarrhea (27%), rash
(26%), cough (23%), and decreased appetite (22%). In Checkmate 238,
the most common adverse reactions (≥20%) reported in OPDIVO-treated
patients (n=452) vs ipilimumab-treated patients (n=453) were
fatigue (57% vs 55%), diarrhea (37% vs 55%), rash (35% vs 47%),
musculoskeletal pain (32% vs 27%), pruritus (28% vs 37%), headache
(23% vs 31%), nausea (23% vs 28%), upper respiratory infection (22%
vs 15%), and abdominal pain (21% vs 23%). The most common
immune-mediated adverse reactions were rash (16%), diarrhea/colitis
(6%), and hepatitis (3%).
Please see U.S. Full Prescribing Information for OPDIVO.
About IPI-549 and the Ongoing Phase 1/1b Study
IPI-549 is an investigational first-in-class, oral,
immuno-oncology product candidate targeting tumor-associated
myeloid cells through selective phosphoinositide-3-kinase-gamma
(PI3K-gamma) inhibition, thereby reducing pro-tumor macrophage
function and increasing anti-tumor macrophage function. In
preclinical studies, IPI-549 demonstrated the ability to reprogram
macrophages from a pro-tumor (M2), immune suppressive function, to
an anti-tumor (M1) immune activating function and enhance the
activity of, and overcome resistance to, checkpoint inhibitors.i ii
As such, IPI-549 may have the potential to treat a broad range of
solid tumors and represents a potentially additive or synergistic
approach to restoring anti-tumor immunity in combination with other
immunotherapies such as checkpoint inhibitors.
The ongoing Phase 1/1b study being conducted by Infinity is
designed to evaluate the safety, tolerability, activity,
pharmacokinetics and pharmacodynamics of IPI-549 as a monotherapy
and in combination with nivolumab (Opdivo®) in approximately 200
patients with advanced solid tumors.iii. The study includes
monotherapy and combination dose-escalation components, in addition
to monotherapy expansion and combination expansion components. The
monotherapy dose-escalation and expansion components are complete.
The combination dose-escalation component is also complete, and the
combination expansion component is enrolling.
The combination expansion component of the study includes
multiple cohorts designed to evaluate IPI-549 in patients with
specific types of cancer, including patients with non-small cell
lung cancer (NSCLC), melanoma and head and neck cancer whose tumors
show initial resistance or initially respond to but subsequently
develop resistance to immune checkpoint blockade therapy. The
combination expansion component also includes a cohort of patients
with triple negative breast cancer (TNBC) who have not been
previously treated with immune checkpoint blockade therapy, a
cohort of patients with mesothelioma, a cohort of patients with
adrenocortical carcinoma and a cohort of patients with high
baseline blood levels of MDSCs.
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.
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 Infinity
Infinity is an innovative biopharmaceutical company dedicated to
advancing novel medicines for people with cancer. Infinity is
advancing IPI-549, an oral immuno-oncology development candidate
that selectively inhibits PI3K-gamma. A Phase 1/1b study in
approximately 200 patients with advanced solid tumors is ongoing.
For more information on Infinity, please refer to Infinity’s
website at www.infi.com.
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 the Opdivo plus IPI-549 combination will receive
regulatory approval in the US 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,
2017 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 as that
term is defined in 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 Opdivo; clinical trial plans
regarding IPI-549; and the company's ability to execute on its
strategic plans. Such statements are subject to numerous important
factors, risks and uncertainties that may cause actual events or
results to differ materially from the company's current
expectations. For example, there can be no guarantee that IPI-549
will successfully complete necessary preclinical and clinical
development phases or that the combination of IPI-549 and
Opdivo will receive regulatory approval for any of the indications
described in this release. Further, there can be no guarantee that
any positive developments in Infinity's product portfolio will
result in stock price appreciation. 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; 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
IPI-549. These and other risks which may impact management's
expectations are described in greater detail under the caption
"Risk Factors" included in Infinity's quarterly report on Form 10-Q
filed with the Securities and Exchange Commission (SEC)
on August 7, 2018, 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.
1
https://www.fda.gov/drugs/informationondrugs/approveddrugs/ucm539646.htm2
Sharma et al. AACR Annual Meeting 20183 Sullivan et al., ASCO 20184
Sullivan et al., ASCO 2018i Kaneda, M., Messer, K.,
Ralainirina, N., Li, H., et al. PI3Kγ is a molecular switch that
controls immune suppression. Nature, 2016
Nov;539:437–442.ii De Henau, O., Rausch, M., Winkler, D.,
Campesato, L., et al. Overcoming resistance to checkpoint blockade
therapy by targeting PI3Kγ in myeloid cells. Nature, 2016
Nov;539:443-447.iii www.clinicaltrials.gov, NCT02637531.
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version on businesswire.com: https://www.businesswire.com/news/home/20181105005135/en/
Bristol-Myers Squibb CompanyMedia:Lisa McCormick
Lavery,
609-252-7602lisa.mccormicklavery@bms.comorInvestors:Tim
Power, 609-252-7509timothy.power@bms.comorBill Szablewski,
609-252-5894william.szablewski@bms.comorInfinity
PharmaceuticalsStern Investor Relations, Inc.Stephanie Ascher,
212-362-1200stephanie@sternir.com
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