NATIONAL HARBOR, Md., Nov. 10,
2017 /PRNewswire/ -- Infinity Pharmaceuticals, Inc.
(NASDAQ: INFI) today reported Phase 1 clinical and translational
data for IPI-549, an oral, selective
phosphoinositide-3-kinase-gamma (PI3K-gamma) inhibitor that targets
immune-suppressive tumor macrophages. These data from the recently
completed monotherapy dose-escalation component of the Phase 1/1b
study demonstrated that IPI-549 dosed once daily (QD) was well
tolerated and clinically active. Among 18 patients evaluable for
activity, there was a 44 percent clinical benefit rate, defined as
patients who had remained on treatment for at least 16 weeks,
including one partial response in a patient with advanced
peritoneal mesothelioma. Additionally, initial translational data
from patient blood samples demonstrated that IPI-549 treatment
results in immune stimulation, with early evidence of biological
activity correlating with clinical benefit. The late-breaking
abstract describing these findings will be presented today in an
oral presentation during the "Clinical Trials: New Agents" session
at the 2017 Society for Immunotherapy of Cancer (SITC) Annual
Meeting taking place in National Harbor, MD, November 10 – 12. IPI-549 is believed to be the
only selective PI3K-gamma inhibitor in clinical development.
"As the majority of patients treated with IPI-549 monotherapy
have advanced forms of cancer and received several therapies prior
to enrollment in this study, it's very encouraging that 44 percent
of patients stayed on treatment for at least 16 weeks, including a
patient with a partial response who has remained on treatment for
over a year and continues on study today," stated David Hong, M.D., Deputy Chair, Department of
Investigational Cancer Therapeutics, Division of Cancer Medicine,
The University of Texas MD Anderson
Cancer Center, Houston, TX. "There
is a significant need for better treatment options for patients,
especially for patients who do not respond to, or develop
resistance to, existing immunotherapies as well as for types of
cancer where there is limited benefit from treatment with
checkpoint inhibitors. Selective inhibition of PI3K-gamma is
emerging as an exciting new approach to inducing an immune
response, and I look forward to my continued participation in this
study."
Infinity is evaluating IPI-549 as a monotherapy and in
combination with Opdivo® (nivolumab), a PD-1 immune
checkpoint inhibitor, in a Phase 1/1b study in approximately 200
patients with advanced solid tumors. The study includes four parts:
monotherapy dose escalation, monotherapy expansion, combination
dose escalation and combination expansion. Infinity has completed
the monotherapy dose escalation, and the monotherapy expansion
component of the study is underway. Infinity expects to complete
the combination dose escalation and initiate the combination
expansion cohorts by the end of 2017. To date, IPI-549 has been
well tolerated as a monotherapy and in combination with Opdivo.
Infinity also announced today that it is adding two additional
cohorts to the combination expansion component of the study, one in
mesothelioma and one in adrenocortical carcinoma (cancer of the
adrenal gland). These two new cohorts are based in part on the
partial response reported in a patient with mesothelioma in the
monotherapy dose-escalation portion of the study and a partial
response in a patient with adrenocortical carcinoma in the
combination dose-escalation component of the study. Both
mesothelioma and adrenocortical carcinoma represent underserved
patient populations.
"An important feature of our clinical trial is that it has a
flexible design that allows us to continue to be data-driven in
adding additional cohorts in response to evidence of clinical
activity and medical need," stated Adelene
Perkins, chief executive officer at Infinity. "In
particular, patients with mesothelioma and adrenocortical carcinoma
have limited effective treatment options, and our early evidence of
activity suggest the potential for IPI-549 to improve outcomes for
these patients."
"We are very pleased with how the Phase 1/1b study of IPI-549
continues to progress, and we anticipate additional results
throughout 2018 from the monotherapy expansion cohort as well as
data from the combination dose escalation and disease-specific
expansion cohorts," Ms. Perkins continued.
Based on progress made during 2017, Infinity expects to achieve
the following IPI-549 data milestones in 2018:
- Report data from the monotherapy expansion component of the
study in the first half of 2018
- Report data from the combination dose-escalation component of
the study in the first half of 2018
- Report initial data from the combination expansion component of
the study in the first half of 2018
- Report additional data from at least six combination expansion
cohorts, with more mature clinical and translational data,
including insights from paired tumor biopsies, in the second half
of 2018
Details of Today's Late-Breaking Abstract
In an oral presentation entitled "Monotherapy dose escalation
clinical and translational data from first-in-human study in
advanced solid tumors of IPI-549, an oral, selective, PI3K-gamma
inhibitor targeting tumor macrophages" (Abstract O43), Dr. Hong
will discuss clinical and translational data from the monotherapy
dose escalation of the Phase 1/1b study of IPI-549. The data
reported today from an October 18,
2017, data cutoff included 19 patients evaluable for safety
and 18 patients evaluable for activity who received monotherapy
doses of IPI-549 ranging from 10 mg to 60 mg QD.
Summary of Clinical Data
Data from the monotherapy dose escalation demonstrated that
IPI-549 treatment was well tolerated. Among 19 patients evaluable
for safety, no dose limiting toxicities were identified, and a
maximum tolerated dose was not reached. The majority of side
effects reported were Grade 1 or Grade 2, and there were no
treatment-related serious adverse events or deaths. The
pharmacokinetic and pharmacodynamic properties of IPI-549 appeared
favorable, with near-complete and sustained inhibition of
PI3K-gamma at doses at or above 20 mg QD, supporting once daily
dosing of IPI-549. Based on these findings, IPI-549 dosed at 60 mg
QD was selected as the recommended monotherapy Phase 2 dose. The
monotherapy expansion component of the study is currently
ongoing.
Among 18 patients evaluable for activity, 44 percent (8 of 18
patients) showed a clinical benefit (defined as patients who
remained on treatment for at least 16 weeks), including one partial
response in a patient with advanced peritoneal mesothelioma who has
remained on treatment for over one year.
Summary of Translational Data
Peripheral blood samples from patients treated with IPI-549 were
analyzed to characterize the potential mechanism of immune
response. Data showed that IPI-549 treatment resulted in immune
stimulation, with upregulation of interferon-gamma responsive
factors and reinvigoration of exhausted T cells across multiple
tumor types and dose levels. Additionally, initial translational
data showed clinical benefit was associated with increased numbers
of immune-stimulated monocytes, suggesting a biologic correlate in
patients who remained on treatment longer. Infinity is continuing
its translational analyses and expects to report additional
findings in 2018.
Infinity Investor/Analyst Reception and Webcast
In conjunction with the 2017 SITC Annual Meeting, Infinity will
host a reception and webcast for investors and analysts today,
November 10, 2017, from 6:00 a.m. ET to 8:00 a.m. ET to discuss the
clinical development of IPI-549, including a review of data from
the Phase 1/1b clinical study. The presentation portion of the
reception will be webcast beginning at 6:30
a.m. ET.
Featured speakers will include:
- David Hong, M.D., Deputy Chair,
Department of Investigational Cancer Therapeutics, Division of
Cancer Medicine, The University of
Texas MD Anderson Cancer Center, Houston, TX
- Taha Merghoub, Ph.D., Co-Director, Ludwig Collaborative
Laboratory and the Swim Across America Laboratory at Memorial Sloan
Kettering
The webcast and accompanying slides can be accessed in the
"investors/media" section of the company's website, www.infi.com. A
replay of the event will also be available.
About the IPI-549 and the Ongoing Phase 1/1b Study
IPI-549 is an investigational, orally administered
immuno-oncology development candidate that selectively inhibits
PI3K-gamma. In preclinical studies, IPI-549 reprograms macrophages
from a pro-tumor, M2, to an anti-tumor, M1, phenotype and is able
to overcome resistance to checkpoint inhibition as well as to
enhance the activity of checkpoint inhibitors.1,2 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 Opdivo in approximately 200 patients with
advanced solid tumors.3 The four-part study includes
monotherapy and combination dose-escalation components, in addition
to monotherapy expansion and combination expansion components.
Patient enrollment is complete in monotherapy dose-escalation, and
monotherapy expansion is ongoing. Combination dose-escalation is
also ongoing, and combination expansion is expected to begin this
year.
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 squamous cell
carcinoma (HNSCC) 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 and a cohort of
patients with adrenocortical carcinoma.
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 Infinity Pharmaceuticals, Inc.
Infinity is an innovative biopharmaceutical company dedicated to
advancing novel medicines for people with cancer. Infinity is
developing IPI-549, an oral immuno-oncology development candidate
that selectively inhibits PI3K-gamma. A Phase 1 study in patients
with advanced solid tumors is ongoing. For more information on
Infinity, please refer to Infinity's website at www.infi.com.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within
the meaning of The Private Securities Litigation Reform Act of
1995. Such forward-looking statements include those regarding: the
therapeutic potential of PI3K-gamma selective inhibition and
IPI-549, alone and in combination with checkpoint inhibitors,
including Opdivo® (nivolumab); clinical trial plans
regarding IPI-549; plans to report clinical and translational data
of 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 or that any
positive developments in Infinity's product portfolio or other
strategic options Infinity may pursue 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, including subsequent analysis of
existing data and new data received from ongoing and future
studies; the content and timing of decisions made by the
U.S. FDA and other regulatory authorities; Infinity's
ability to obtain and maintain requisite regulatory approvals and
to enroll patients in its clinical trials; unplanned cash
requirements and expenditures; development of agents by Infinity's
competitors for diseases in which Infinity is currently developing
or intends to develop IPI-549; and Infinity's ability to obtain,
maintain and enforce patent and other intellectual property
protection for 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 November 7, 2017, 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.
OPDIVO® is a registered trademark of Bristol-Myers
Squibb.
1 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.
2 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.
3 www.clinicaltrials.gov, NCT02637531.
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SOURCE Infinity Pharmaceuticals, Inc.