NEW YORK and CAMBRIDGE, Mass., Nov.
5, 2018 /PRNewswire/ -- 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 (nivolumab) 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.
Contacts:
Bristol-Myers Squibb
Company
Media:
Lisa
McCormick Lavery, 609-252-7602,
lisa.mccormicklavery@bms.com
Investors:
Tim Power,
609-252-7509, timothy.power@bms.com
Bill Szablewski, 609-252-5894,
william.szablewski@bms.com
Infinity Pharmaceuticals
Stephanie Ascher, Stern Investor Relations,
Inc.
212-362-1200 or stephanie@sternir.com
1
https://www.fda.gov/drugs/informationondrugs/approveddrugs/ucm539646.htm
2 Sharma et al. AACR Annual Meeting 2018
3 Sullivan et al., ASCO 2018
4 Sullivan et al., ASCO 2018
i 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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SOURCE Infinity Pharmaceuticals, Inc.