BOSTON–(BUSINESS WIRE)– Verastem, Inc. (Nasdaq:VSTM) (Verastem Oncology or the Company), a
biopharmaceutical company focused on developing and commercializing
medicines seeking to improve the survival and quality of life of cancer
patients, today announced that the results of the Phase 2 DYNAMO™ study,
which evaluated COPIKTRA™ (duvelisib) capsules in patients with indolent
non-Hodgkin lymphoma (iNHL) who were refractory to both rituximab and
chemotherapy or radioimmunotherapy, was published online in the
[peer-reviewed] Journal of Clinical Oncology. COPIKTRA received
accelerated approval from the U.S. Food and Drug Administration on
September 24, 2018 for the treatment of adult patients with relapsed or
refractory follicular lymphoma (FL) after at least two prior systemic
therapies. Additionally, COPIKTRA is indicated for the treatment of
adult patients with chronic lymphocytic leukemia (CLL) or small
lymphocytic leukemia (SLL) after at least two prior therapies.
COPIKTRA is an oral inhibitor of phosphoinositide 3-kinase (PI3K), a
dual inhibitor of both PI3K-delta and PI3K-gamma. The COPIKTRA New Drug
Application (NDA) was supported by clinical data from the open-label,
single-arm Phase 2 DYNAMO study (NCT01882803), which evaluated the
efficacy and safety of COPIKTRA (25mg twice daily) as a monotherapy in
129 adult patients with various types of iNHL, including follicular
lymphoma (FL; n=83), small lymphocytic lymphoma (SLL; n=28) or marginal
zone lymphoma (MZL; n=18), whose disease had progressed and who were
refractory to rituximab and to either chemotherapy or
radioimmunotherapy. The primary endpoint of the study was ORR as
assessed by an independent review committee (IRC).
“Indolent non-Hodgkin lymphoma remains largely incurable and often
requires multiple lines of treatment after becoming refractory to
standard therapies,” said Ian Flinn, M.D., Ph.D., Director of the
Lymphoma Research Program at Sarah Cannon Research Institute, lead
investigator of the Phase 2 DYNAMO study and lead author of the
manuscript. “In the DYNAMO study, oral duvelisib monotherapy
demonstrated clinically meaningful activity and a manageable safety
profile in heavily pretreated, double-refractory iNHL, including in
patients with SLL, FL and MZL. Duvelisib is an important addition to the
evolving treatment paradigm for patients with FL and we are delighted to
have the study results published in this prestigious journal to share
with the medical and scientific communities.”
While MZL patients were included in the DYNAMO study, COPIKTRA has not
been deemed safe and effective by the FDA for use in treating patients
suffering from MZL, however, MZL represents a potential new patient
indication that may benefit from COPIKTRA.
The National Comprehensive Cancer Network® (NCCN) has added COPIKTRA to
the Clinical Practice Guidelines in Oncology (NCCN Guidelines) for
CLL/SLL, FL and MZL. The NCCN Guidelines are the standard physician
resource for determining the appropriate course of treatment for
The full manuscript, titled “DYNAMO: A Phase II Study of Duvelisib
(IPI-145) in Patients With Refractory Indolent Non-Hodgkin Lymphoma,”
(Flinn, et al. DOI: 10.1200/JCO.18.00915) can be accessed here.
Results of the Phase 2 DYNAMO Study in iNHL
The ORR per IRC-assessed response was 47% (95% CI, 38% to 56%). The
study met its primary end point (p<0.001). ORR per IRC was 42%, 68%, and
39% in FL, SLL, and MZL subtypes, respectively. Responses were rapid and
durable. Median time to response (TTR) was 1.87 months (range, 1.4 to
11.7 months), with 59% and 84% of patients responding by 2 and 4 months,
respectively. Median duration of response (DOR) was 10 months (95% CI,
6.5 to 10.5 months), with estimated probabilities of remaining in
response at 6 and 12 months of 69% and 35%. Median PFS was 9.5 months
(95% CI, 8.1 to 11.8 months), with the probability of surviving and
being progression free at 6 months estimated at 62%. Median overall
survival (OS) was 28.9 months (95% CI, 21.4 months to not estimable),
and OS at 1 year was estimated at 77%. Among the 39 patients with FL who
received an R-CHOP (or equivalent) chemoimmunotherapy regimen as first
therapy, 30 (77%) experienced early relapse (no response during
treatment or progressive disease or time to next treatment less than 2
years). This patient subgroup showed an ORR of 33%, median DOR of 12.6
months and median PFS of 8.2 months. The approval and corresponding
label of COPIKTRA in FL was based on the efficacy and safety results
from the FL patients (n=83) in DYNAMO that had received at least two
prior systemic therapies. The accelerated approval was based on overall
response rate (ORR) and continued approval may be contingent upon
verification and description of clinical benefit in confirmatory trials.
COPIKTRA is not FDA approved for MZL.
COPIKTRA contains a BOXED WARNING for four fatal and/or serious
toxicities: infections, diarrhea or colitis, cutaneous reactions, and
pneumonitis. More information about these Boxed Warnings and additional
Important Safety Information can be found below and in the full
Prescribing Information at www.COPIKTRA.com.Verastem
Oncology is implementing a Risk Evaluation and Mitigation Strategy to
provide appropriate dosing and safety information to better support
physicians in managing their patients on COPIKTRA.
COPIKTRA is associated with adverse reactions which may require dose
reduction, treatment delay or discontinuation of COPIKTRA. In addition
to the BOXED WARNING, COPIKTRA has WARNINGS AND PRECAUTIONS for
hepatotoxicity, neutropenia, and embryo-fetal toxicity. The most common
ADVERSE REACTIONS (reported in ? 20% of patients) were diarrhea or
colitis, neutropenia, rash, fatigue, pyrexia, cough, nausea, upper
respiratory infection, pneumonia, musculoskeletal pain, and anemia.
Please see important Safety Information provided below and Prescribing
Information including BOXED WARNING and Medication Guide at www.COPIKTRAHCP.com/prescribinginformation
About Follicular Lymphoma
Follicular lymphoma (FL) is typically a slow-growing or indolent form of
non-Hodgkin lymphoma (NHL) that arises from B-lymphocytes, making it a
B-cell lymphoma. This lymphoma subtype accounts for 20 to 30 percent of
all NHL cases, with more than 140,000 people in the US with FL and more
than 13,000 newly diagnosed patients this year. Common symptoms of FL
include enlargement of the lymph nodes in the neck, underarms, abdomen,
or groin, as well as fatigue, shortness of breath, night sweats, and
weight loss. Often, patients with FL have no obvious symptoms of the
disease at diagnosis. Follicular lymphoma is usually not considered to
be curable, but more of a chronic disease, with patients living for many
years with this form of lymphoma. The potential of additional oral
agents, particularly as a monotherapy that can be used in the general
community physician’s armamentarium, may hold significant value in the
treatment of patients with FL.
About COPIKTRA™ (duvelisib)
COPIKTRA is an oral inhibitor of phosphoinositide 3-kinase (PI3K), and
the first approved dual inhibitor of PI3K-delta and PI3K-gamma, two
enzymes known to help support the growth and survival of malignant
B-cells. PI3K signaling may lead to the proliferation of malignant
B-cells and is thought to play a role in the formation and maintenance
of the supportive tumor microenvironment.1,2,3 COPIKTRA is
indicated for the treatment of adult patients with relapsed or
refractory chronic lymphocytic leukemia/small lymphocytic lymphoma
(CLL/SLL) after at least two prior therapies and relapsed or refractory
follicular lymphoma (FL) after at least two prior systemic therapies.
COPIKTRA is also being developed by Verastem Oncology for the treatment
of peripheral T-cell lymphoma (PTCL), for which it has received Fast
Track status, and is being investigated in combination with other agents
through investigator-sponsored studies.4 For more information
on COPIKTRA, please visit www.COPIKTRA.com.
Information about duvelisib clinical trials can be found on www.clinicaltrials.gov.
About Verastem Oncology
Verastem Oncology (Nasdaq: VSTM) is a commercial biopharmaceutical
company committed to the development and commercialization of medicines
to improve the lives of patients diagnosed with cancer. We are driven by
the strength, tenacity and courage of those battling cancer –
single-minded in our resolve to deliver new therapies that not only keep
cancer at bay, but improve the lives of patients diagnosed with cancer.
Because for us, it’s personal.
Our first FDA approved product is now available for the treatment of
patients with certain types of indolent non-Hodgkin’s lymphoma (iNHL).
Our pipeline comprises product candidates that seek to treat cancer by
modulating the local tumor microenvironment. For more information,
please visit www.verastem.com.
Important Safety Information
WARNING: FATAL AND SERIOUS TOXICITIES: INFECTIONS, DIARRHEA OR COLITIS,
CUTANEOUS REACTIONS, and PNEUMONITIS
Fatal and/or serious infections occurred in 31% of COPIKTRA-treated
patients. Monitor for signs and symptoms of infection. Withhold
COPIKTRA if infection is suspected.
Fatal and/or serious diarrhea or colitis occurred in 18% of
COPIKTRA-treated patients. Monitor for the development of severe
diarrhea or colitis. Withhold COPIKTRA.
Fatal and/or serious cutaneous reactions occurred in 5% of
COPIKTRA-treated patients. Withhold COPIKTRA.
Fatal and/or serious pneumonitis occurred in 5% of COPIKTRA-treated
patients. Monitor for pulmonary symptoms and interstitial infiltrates.
WARNINGS AND PRECAUTIONS
Infections: Serious, including fatal (18/442; 4%), infections
occurred in 31% of patients receiving COPIKTRA 25 mg BID (N=442). The
most common serious infections were pneumonia, sepsis, and lower
respiratory infections. Median time to onset of any grade infection was
3 months (range: 1 day to 32 months), with 75% of cases occurring within
6 months. Treat infections prior to initiation of COPIKTRA. Advise
patients to report new or worsening signs and symptoms of infection. For
grade 3 or higher infection, withhold COPIKTRA until infection has
resolved. Resume COPIKTRA at the same or reduced dose.
Serious, including fatal, Pneumocystis jirovecii pneumonia (PJP)
occurred in 1% of patients taking COPIKTRA. Provide prophylaxis for PJP
during treatment with COPIKTRA and following completion of treatment
with COPIKTRA until the absolute CD4+ T cell count is greater than 200
cells/?L. Withhold COPIKTRA in patients with suspected PJP of any grade,
and permanently discontinue if PJP is confirmed.
Cytomegalovirus (CMV) reactivation/infection occurred in 1% of patients
taking COPIKTRA. Consider prophylactic antivirals during COPIKTRA
treatment to prevent CMV infection including CMV reactivation. For
clinical CMV infection or viremia, withhold COPIKTRA until infection or
viremia resolves. If COPIKTRA is resumed, administer the same or reduced
dose and monitor patients for CMV reactivation by PCR or antigen test at
Diarrhea or Colitis: Serious, including fatal (1/442; <1%),
diarrhea or colitis occurred in 18% of patients receiving COPIKTRA 25 mg
BID (N=442). Median time to onset of any grade diarrhea or colitis was 4
months (range: 1 day to 33 months), with 75% of cases occurring by 8
months. The median event duration was 0.5 months (range: 1 day to 29
months; 75th percentile: 1 month).
Advise patients to report any new or worsening diarrhea. For patients
presenting with mild or moderate diarrhea (Grade 1-2) (i.e., up to 6
stools per day over baseline) or asymptomatic (Grade 1) colitis,
initiate supportive care with antidiarrheal agents, continue COPIKTRA at
the current dose, and monitor the patient at least weekly until the
event resolves. If the diarrhea is unresponsive to antidiarrheal
therapy, withhold COPIKTRA and initiate supportive therapy with enteric
acting steroids (e.g., budesonide). Monitor the patient at least weekly.
Upon resolution of the diarrhea, consider restarting COPIKTRA at a
For patients presenting with abdominal pain, stool with mucus or blood,
change in bowel habits, peritoneal signs, or with severe diarrhea (Grade
3) (i.e., > 6 stools per day over baseline), withhold COPIKTRA and
initiate supportive therapy with enteric acting steroids (e.g.,
budesonide) or systemic steroids. A diagnostic work-up to determine
etiology, including colonoscopy, should be performed. Monitor at least
weekly. Upon resolution of the diarrhea or colitis, restart COPIKTRA at
a reduced dose. For recurrent Grade 3 diarrhea or recurrent colitis of
any grade, discontinue COPIKTRA. Discontinue COPIKTRA for
life-threatening diarrhea or colitis.
Cutaneous Reactions: Serious, including fatal (2/442; <1%),
cutaneous reactions occurred in 5% of patients receiving COPIKTRA 25 mg
BID (N=442). Fatal cases included drug reaction with eosinophilia and
systemic symptoms (DRESS) and toxic epidermal necrolysis (TEN). Median
time to onset of any grade cutaneous reaction was 3 months (range: 1 day
to 29 months, 75th percentile: 6 months) with a median event duration of
1 month (range: 1 day to 37 months, 75th percentile: 2 months).
Presenting features for the serious events were primarily described as
pruritic, erythematous, or maculo-papular. Less common presenting
features include exanthem, desquamation, erythroderma, skin exfoliation,
keratinocyte necrosis, and papular rash. Advise patients to report new
or worsening cutaneous reactions. Review all concomitant medications and
discontinue any medications potentially contributing to the event. For
patients presenting with mild or moderate (Grade 1-2) cutaneous
reactions, continue COPIKTRA at the current dose, initiate supportive
care with emollients, antihistamines (for pruritus), or topical
steroids, and monitor the patient closely. Withhold COPIKTRA for severe
(Grade 3) cutaneous reaction until resolution. Initiate supportive care
with steroids (topical or systemic) or antihistamines (for pruritus).
Monitor at least weekly until resolved. Upon resolution of the event,
restart COPIKTRA at a reduced dose. Discontinue COPIKTRA if severe
cutaneous reaction does not improve, worsens, or recurs. For
life-threatening cutaneous reactions, discontinue COPIKTRA. In patients
with SJS, TEN, or DRESS of any grade, discontinue COPIKTRA.
Pneumonitis: Serious, including fatal (1/442; <1%), pneumonitis
without an apparent infectious cause occurred in 5% of patients
receiving COPIKTRA 25 mg BID (N=442). Median time to onset of any grade
pneumonitis was 4 months (range: 9 days to 27 months), with 75% of cases
occurring within 9 months. The median event duration was 1 month, with
75% of cases resolving by 2 months.
Withhold COPIKTRA in patients with new or progressive pulmonary signs
and symptoms such as cough, dyspnea, hypoxia, interstitial infiltrates
on a radiologic exam, or a decline by more than 5% in oxygen saturation,
and evaluate for etiology. If the pneumonitis is infectious, patients
may be restarted on COPIKTRA at the previous dose once the infection,
pulmonary signs and symptoms resolve. For moderate non-infectious
pneumonitis (Grade 2), treat with systemic corticosteroids and resume
COPIKTRA at a reduced dose upon resolution. If non-infectious
pneumonitis recurs or does not respond to steroid therapy, discontinue
COPIKTRA. For severe or life-threatening non-infectious pneumonitis,
discontinue COPIKTRA and treat with systemic steroids.
Hepatotoxicity: Grade 3 and 4 ALT and/or AST elevation developed
in 8% and 2%, respectively, of patients receiving COPIKTRA 25 mg BID
(N=442). Two percent of patients had both an ALT or AST > 3 X ULN and
total bilirubin > 2 X ULN. Median time to onset of any grade
transaminase elevation was 2 months (range: 3 days to 26 months), with a
median event duration of 1 month (range: 1 day to 16 months).
Monitor hepatic function during treatment with COPIKTRA. For Grade 2
ALT/AST elevation (> 3 to 5 X ULN), maintain COPIKTRA dose and monitor
at least weekly until return to < 3 X ULN. For Grade 3 ALT/AST elevation
(> 5 to 20 X ULN), withhold COPIKTRA and monitor at least weekly until
return to < 3 X ULN. Resume COPIKTRA at the same dose (first occurrence)
or at a reduced dose for subsequent occurrences. For grade 4 ALT/AST
elevation (> 20 X ULN), discontinue COPIKTRA.
Neutropenia: Grade 3 or 4 neutropenia occurred in 42% of patients
receiving COPIKTRA 25 mg BID (N=442), with Grade 4 neutropenia occurring
in 24% of all patients. Median time to onset of grade ?3 neutropenia was
2 months (range: 3 days to 31 months), with 75% of cases occurring
within 4 months.
Monitor neutrophil counts at least every 2 weeks for the first 2 months
of COPIKTRA therapy, and at least weekly in patients with neutrophil
counts < 1.0 Gi/L (Grade 3-4). Withhold COPIKTRA in patients presenting
with neutrophil counts < 0.5 Gi/L (Grade 4). Monitor until ANC is > 0.5
Gi/L, then resume COPIKTRA at same dose for the first occurrence or at a
reduced dose for subsequent occurrences.
Embryo-Fetal Toxicity: Based on findings in animals and its
mechanism of action, COPIKTRA can cause fetal harm when administered to
a pregnant woman. Advise pregnant women of the potential risk to a
fetus. Conduct pregnancy testing before initiating COPIKTRA treatment.
Advise females of reproductive potential and males with female partners
of reproductive potential to use effective contraception during
treatment and for at least 1 month after the last dose.
B-cell Malignancies Summary
Fatal adverse reactions within 30 days of the last dose occurred in 8%
(36/442) of patients treated with COPIKTRA 25 mg BID. Serious adverse
reactions were reported in 289 patients (65%). The most frequent serious
adverse reactions that occurred were infection (31%), diarrhea or
colitis (18%), pneumonia (17%), rash (5%), and pneumonitis (5%).
Adverse reactions resulted in treatment discontinuation in 156 patients
(35%) most often due to diarrhea or colitis, infection, and rash.
COPIKTRA was dose reduced in 104 patients (24%) due to adverse
reactions, most often due to diarrhea or colitis and transaminase
elevation. The most common adverse reactions (reported in ? 20% of
patients) were diarrhea or colitis, neutropenia, rash, fatigue, pyrexia,
cough, nausea, upper respiratory infection, pneumonia, musculoskeletal
pain and anemia.
CLL/SLL: Fatal adverse reactions within 30 days of the last dose
occurred in 12% (19/158) of patients treated with COPIKTRA and in 4%
(7/155) of patients treated with ofatumumab. Serious adverse reactions
were reported in 73% (115/158) of patients treated with COPIKTRA and
most often involved infection (38%; 60/158) and diarrhea or colitis
(23%; 36/158). COPIKTRA was discontinued in 57 patients (36%), most
often due to diarrhea or colitis, infection, and rash. COPIKTRA was dose
reduced in 46 patients (29%) due to adverse reactions, most often due to
diarrhea or colitis and rash. The most common adverse reactions with
COPIKTRA (reported in ?20% of patients) were diarrhea or colitis,
neutropenia, pyrexia, upper respiratory tract infection, pneumonia,
rash, fatigue, nausea, anemia and cough.
FL: Serious adverse reactions were reported in 58% of patients
and most often involved diarrhea or colitis, pneumonia, renal
insufficiency, rash, and sepsis. The most common adverse reactions (?20%
of patients) were diarrhea or colitis, nausea, fatigue, musculoskeletal
pain, rash, neutropenia, cough, anemia, pyrexia, headache, mucositis,
abdominal pain, vomiting, transaminase elevation, and thrombocytopenia.
Adverse reactions resulted in COPIKTRA discontinuation in 29% of
patients, most often due to diarrhea or colitis and rash. COPIKTRA was
dose reduced in 23% due to adverse reactions, most often due to
transaminase elevation, diarrhea or colitis, lipase increased and
CYP3A Inducers: Coadministration with a strong CYP3A inducer may
reduce COPIKTRA efficacy. Avoid coadministration with strong CYP3A4
CYP3A Inhibitors: Coadministration with a strong CYP3A inhibitor may
increase the risk of COPIKTRA toxicities. Reduce COPIKTRA dose to 15
mg BID when coadministered with a strong CYP3A4 inhibitor.
CYP3A Substrates: Coadministration of COPIKTRA with sensitive CYP3A4
substrates may increase the risk of toxicities of these drugs.
Consider reducing the dose of the sensitive CYP3A4 substrate and
monitor for signs of toxicities of the coadministered sensitive CYP3A
See full Prescribing Information, including Boxed Warning, at www.COPIKTRA.com
Forward looking statements notice
This press release includes forward-looking statements about Verastem
Oncology’s strategy, future plans and prospects, including statements
regarding the development and activity of Verastem Oncology’s lead
product duvelisib, and Verastem Oncology’s PI3K and FAK programs
generally, its intent to commercialize duvelisib, the potential
commercial success of duvelisib, the anticipated adoption of duvelisib
by patients and physicians, the structure of its planned and pending
clinical trials and the timeline and indications for clinical
development, regulatory submissions and commercialization activities.
The words « anticipate, » « believe, » « estimate, » « expect, » « intend, »
« may, » « plan, » « predict, » « project, » « target, » « potential, » « will, »
« would, » « could, » « should, » « continue, » and similar expressions are
intended to identify forward-looking statements, although not all
forward-looking statements contain these identifying words. Each
forward-looking statement is subject to risks and uncertainties that
could cause actual results to differ materially from those expressed or
implied in such statement. Applicable risks and uncertainties include,
among other things, uncertainties regarding the commercial success of
duvelisib in the United States; uncertainties regarding physician and
patient adoption of duvelisib, including those related to the safety and
efficacy of duvelisib; the uncertainties inherent in research and
development of duvelisib, such as negative or unexpected results of
clinical trials; whether and when any applications for duvelisib may be
filed with regulatory authorities in any other jurisdictions; whether
and when regulatory authorities in any other jurisdictions may approve
any such other applications that may be filed for duvelisib, which will
depend on the assessment by such regulatory authorities of the
benefit-risk profile suggested by the totality of the efficacy and
safety information submitted and, if approved, whether duvelisib will be
commercially successful in such jurisdictions; Verastem Oncology’s
ability to obtain, maintain and enforce patent and other intellectual
property protection for duvelisib and its other product candidates; the
scope, timing, and outcome of any legal proceedings; decisions by
regulatory authorities regarding labeling and other matters that could
affect the availability or commercial potential of duvelisib; that
regulatory authorities in the U.S. or other jurisdictions, if approved,
could withdraw approval; whether preclinical testing of Verastem
Oncology’s product candidates and preliminary or interim data from
clinical trials will be predictive of the results or success of ongoing
or later clinical trials; that the timing, scope and rate of
reimbursement for Verastem Oncology’s product candidates is uncertain;
the risk that third party payors (including government agencies) will
not reimburse for duvelisib; that there may be competitive developments
affecting its product candidates; that data may not be available when
expected; that enrollment of clinical trials may take longer than
expected; that duvelisib or Verastem Oncology’s other product candidates
will cause unexpected safety events, experience manufacturing or supply
interruptions or failures, or result in unmanageable safety profiles as
compared to their levels of efficacy; that duvelisib will be ineffective
at treating patients with lymphoid malignancies; that Verastem Oncology
will be unable to successfully initiate or complete the clinical
development and eventual commercialization of its product candidates;
that the development and commercialization of Verastem Oncology’s
product candidates will take longer or cost more than planned; that
Verastem Oncology may not have sufficient cash to fund its contemplated
operations; that Verastem Oncology or Infinity Pharmaceuticals, Inc.
will fail to fully perform under the duvelisib license agreement; that
Verastem Oncology may be unable to make additional draws under its debt
facility or obtain adequate financing in the future through product
licensing, co-promotional arrangements, public or private equity, debt
financing or otherwise; that Verastem Oncology will not pursue or submit
regulatory filings for its product candidates, including for duvelisib
in patients with CLL/SLL or FL in other jurisdictions; and that Verastem
Oncology’s product candidates will not receive regulatory approval,
become commercially successful products, or result in new treatment
options being offered to patients.
Other risks and uncertainties include those identified under the heading
« Risk Factors » in the Company’s Quarterly Report on Form 10-Q for the
quarterly period ended September 30, 2018 as filed with the Securities
and Exchange Commission (SEC) on November 7, 2018, its Annual Report on
Form 10-K for the year ended December 31, 2017 as filed with the SEC on
March 13, 2018 and in any subsequent filings with the SEC. The
forward-looking statements contained in this press release reflect
Verastem Oncology’s views as of the date hereof, and the Company does
not assume and specifically disclaims any obligation to update any
forward-looking statements whether as a result of new information,
future events or otherwise, except as required by law.
1 Winkler D.G., Faia K.L., DiNitto J.P. et al.
PI3K-delta and PI3K-gamma inhibition by IPI-145 abrogates immune
responses and suppresses activity in autoimmune and inflammatory disease
models. Chem Biol 2013; 20:1-11.
2 Reif K et al. Cutting Edge: Differential Roles for
Phosphoinositide 3 kinases, p110-gamma and p110-delta, in lymphocyte
chemotaxis and homing. J Immunol 2004:173:2236-2240.
3 Schmid M et al. Receptor Tyrosine Kinases and TLR/IL1Rs
Unexpectedly activate myeloid cell PI3K, a single convergent point
promoting tumor inflammation and progression. Cancer Cell
Source: Verastem, Inc.