-- Plans to Initiate MARIO-275, a Randomized, Global Phase 2 Study in
1H’19--
NEW YORK & CAMBRIDGE, Mass.--(BUSINESS WIRE)--
Bristol-Myers
Squibb Company (NYSE: BMY) and Infinity Pharmaceuticals, Inc.
(NASDAQ: INFI) today announced a clinical trial collaboration to
evaluate Bristol-Myers Squibb's Opdivoin 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
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2
Sharma et al. AACR Annual Meeting 2018
3 Sullivan et
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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
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iii www.clinicaltrials.gov,
NCT02637531.
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