Verastem Oncology Presents COPIKTRA™ (Duvelisib) Data at the European Hematology Association 2019 Annual Meeting

In CLL/SLL Patients in the DUO Study, Duvelisib Treatment Rapidly
Increased Lymphocytes and Resulted in Shrinkage of Lymph Nodes, With 86%
of Patients Achieving a Lymph Node Response

Dose Modifications Utilized in the DUO Study May Be Used to Manage
Adverse Events for CLL/SLL Patients Receiving COPIKTRA

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 two posters highlighting clinical data
for COPIKTRA™ (duvelisib) in patients with relapsed or refractory
chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) were
presented at the European Hematology Association (EHA) 2019 Annual
Meeting which took place June 13-16, 2019, in Amsterdam. One poster
describes results from a post-hoc analysis evaluating the effect of
COPIKTRA on lymphocytosis in patients with relapsed or refractory
CLL/SLL from the Phase 3 DUO study, including patients with high-risk
factors. The other poster describes dose modification data from patients
with relapsed or refractory CLL/SLL in the DUO study.

COPIKTRA, a targeted oral inhibitor of phosphoinositide 3-kinase (PI3K),
and the first approved dual inhibitor of PI3K-delta and PI3K-gamma,
received approval as monotherapy from the U.S. Food and Drug
Administration (FDA) in September 2018 for the treatment of patients
with relapsed or refractory CLL/SLL after at least two prior therapies.

“Duvelisib is a potent oral dual inhibitor of PI3K-delta and -gamma with
clinical activity in patients with CLL/SLL after at least two prior
therapies,” said Hagop Youssoufian, MSc, M.D., Head of Medical Strategy
at Verastem Oncology. “In a post-hoc analysis authored by Dr. Barrientos
and colleagues, duvelisib induced rapid and transient lymphocytosis that
was associated with a reduction in lymphadenopathy, including in
high-risk patients. Notably, duvelisib also resulted in resolution of
lymphocytosis at up to 21 weeks, and the majority of patients achieved a
lymph node response and also achieved rapid shrinkage of their lymph
nodes.”

Patterns of Duvelisib-Induced Lymphocytosis in Patients with
Relapsed/Refractory CLL/SLL, Including Those with High-Risk Factors

In this study, researchers aimed to characterize the clinical profile
and kinetics associated with duvelisib-related lymphocytosis.
Lymphocytosis is an increase in the number of lymphocytes (white blood
cells) in the blood and is a recognized biological marker of treatment
with B-cell receptor pathway inhibitors. Similar to ibrutinib and
idelalisib, duvelisib treatment induces lymphocytosis in patients with
CLL. This post hoc analysis defined response in patients (n=158) with
relapsed or refractory CLL/SLL, including high-risk subgroups, which
were characterized by unmutated IGHV (n=110), 17p deletion/TP53 mutation
(n=48), 11q deletion (n=38), and bulky disease (n=74).

Of 158 patients treated with duvelisib, 78% experienced lymphocytosis.
Median time to onset of lymphocytosis was one week across all patients,
including patients in the high-risk subgroups. Median time to resolution
of lymphocytosis was 14 weeks, with a 50% reduction from baseline at 21
weeks. Similar results were observed regardless of high-risk status.
Rapid shrinkage of lymph nodes was noted, with 86% of patients achieving
lymph node response. Among patients who achieved a response with
duvelisib at first or second assessment, 78% and 86%, respectively,
experienced lymphocytosis; median time to resolution of lymphocytosis in
these patients was 12 and 18 weeks, respectively. Prolonged
lymphocytosis (for >12 months) occurred in 12 patients (8%). The overall
response rate in patients with prolonged lymphocytosis was 83%. Of note,
the median PFS was similar among patients with and without prolonged
lymphocytosis; 22.1 months (95% CI, 12.9-27.6), compared to 24 months
(95% CI, 20.5-NE), respectively. Overall, there were low rates of tumor
lysis syndrome (1 patient; 0.6%). These results showed that duvelisib
monotherapy induced rapid and transient lymphocytosis temporally
associated with a reduction in lymphadenopathy in patients with relapsed
or refractory CLL/SLL.

Effect of Dose Modification on Response to COPIKTRA in Patients with
Relapsed or Refractory CLL/SLL in the Phase 3 DUO Study

The randomized, multicenter, open-label, Phase 3 DUO study, compared
COPIKTRA versus ofatumumab in 319 adult patients with CLL (n=312) or SLL
(n=7) after at least one prior therapy. The study randomized patients
with a 1:1 ratio to receive either COPIKTRA 25mg twice daily until
disease progression or unacceptable toxicity, or ofatumumab, an approved
standard of care treatment for use in CLL/SLL, for 7 cycles. This
analysis examined dose modification patterns and their impact on
response to COPIKTRA. Dose interruptions or dose reductions to 15mg,
10mg or 5mg twice daily were permitted per study protocol to manage
treatment-emergent adverse events (TEAEs). Responses were assessed per
an Independent Review Committee.

Among the 158 COPIKTRA-treated patients in the DUO study, the median
duration of exposure was 11.6 months, versus 5.3 months for patients
treated with ofatumumab. The most common cause of dose interruption was
diarrhea (23%), followed by neutropenia (12%) and pneumonia or colitis
(11% each). Among responders (n=118), median time to first response on
COPIKTRA was 1.9 months and the estimated median duration of response
was 11.1 months. Median time to first dose interruption was 3.9 months
and median duration of dose interruption was 15 days (range 1 to 133
days). Response to COPIKTRA was improved or maintained in most patients
evaluated for response who had at least one dose interruption for >1
week (84%) or >2 weeks (82%) followed by at least 3 weeks on COPIKTRA.
In a landmark analysis, median PFS was similar in patients with dose
interruptions and those without dose interruptions for >1 week (17.8
versus 16.3 months) or >2 weeks (17.8 versus 16.3 months) within the
first 3 months. The median time to dose reduction after a complete
response or partial response was 5.6 months (n=25) and median duration
was 3.4 months. Median time to onset across adverse events of special
interest (AESIs) after starting COPIKTRA ranged from 2.2 to 4.3 months.
Median time to resolution was within 4 weeks across AESIs. Proportions
of patients experiencing AESIs were stable or decreased over time after
3-6 months: 0-3 months, 64%; >3-6 months, 63%; >6-9 months, 47%; >9-12
months, 52%, and seldom led to discontinuation of COPIKTRA (≤10%). These
findings support the thesis that dose interruptions or dose reductions
may be useful in managing TEAEs with COPIKTRA and that dose
interruptions of >1-2 weeks or more did not appear to significantly
impact response to COPIKTRA or PFS.

PDF copies of these poster presentations are available here.

Details for the EHA 2019 poster presentations are as follows:

Title: Effect
of dose modifications on response to duvelisib in patients with
relapsed/refractory (R/R) CLL/SLL in the DUO trial

Lead
author:
Paolo Ghia, Università Vita-Salute San Raffaele
Session:
6. Chronic lymphocytic leukemia and related disorders – Clinical
Abstract
#:
PS1157

Title: Patterns
of duvelisib-induced lymphocytosis in patients with relapsed/refractory
chronic lymphocytic leukemia/small lymphocytic leukemia including those
with high-risk factors treated in the DUO trial

Lead author:
Jacqueline Barrientos, Zucker School of Medicine at Hofstra/Northwell
Session:
6. Chronic lymphocytic leukemia and related disorders – Clinical
Abstract
#:
PS1160

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. Withhold COPIKTRA.

 

WARNINGS AND PRECAUTIONS

Infections: Serious, including fatal (4%), infections occurred in
31% of patients receiving COPIKTRA (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, 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. Cases of Pneumocystis jirovecii pneumonia (PJP) (1%) and
cytomegalovirus (CMV) reactivation/infection (1%) occurred in patients
taking COPIKTRA. Provide prophylaxis for PJP during treatment and
following completion of treatment until the absolute CD4+ T cell count
is greater than 200 cells/µL. Consider prophylactic antivirals during
COPIKTRA treatment to prevent CMV infection including CMV reactivation.

Diarrhea or Colitis: Serious, including fatal (<1%), diarrhea or
colitis occurred in 18% of patients receiving COPIKTRA (N=442). Median
time to onset of any grade diarrhea or colitis was 4 months, with 75% of
cases occurring by 8 months. The median event duration was 0.5 months.
Advise patients to report any new or worsening diarrhea.

Cutaneous Reactions: Serious, including fatal (<1%), cutaneous
reactions occurred in 5% of patients receiving COPIKTRA (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 with a median event duration
of 1 month. 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.

Pneumonitis: Serious, including fatal (<1%), pneumonitis without
an apparent infectious cause occurred in 5% of patients receiving
COPIKTRA (N=442). Median time to onset of any grade pneumonitis was 4
months with 75% of cases occurring within 9 months. The median event
duration was 1 month with 75% of cases resolving by 2 months.

Hepatotoxicity: Grade 3 and 4 ALT and/or AST elevation developed
in 8% and 2%, respectively, of patients receiving COPIKTRA (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 with a median event duration of 1 month. Monitor hepatic
function during treatment with COPIKTRA.

Neutropenia: Grade 3 or 4 neutropenia occurred in 42% of patients
receiving COPIKTRA (N=442), with Grade 4 neutropenia occurring in 24% of
all patients. Median time to onset of grade ≥3 neutropenia was 2 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).

Embryo-Fetal Toxicity: COPIKTRA can cause fetal harm when
administered to a pregnant woman. Advise pregnant women of the potential
risk to a fetus and 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.

ADVERSE REACTIONS

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%). 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). The most
common adverse reactions with COPIKTRA (≥20% of patients) were diarrhea
or colitis, neutropenia, pyrexia, upper respiratory tract infection,
pneumonia, rash, fatigue, nausea, anemia and cough.

For specific information on the management of the adverse reactions
above, please review Dose Modifications for Adverse Reactions
within the full Prescribing Information.

DRUG INTERACTIONS

CYP3A Inducers: Coadministration with a strong CYP3A inducer may
reduce COPIKTRA efficacy. Avoid coadministration with strong CYP3A4
inducers.

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 substrate.

To report Adverse Reactions, contact FDA at 1-800-FDA-1088
(1-800-332-1088) or
www.fda.gov/medwatch
and Verastem Oncology at 1-877-7RXVSTM (1-877-779-8786).

Please see accompanying full Prescribing
Information
, including Boxed Warning.

About Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL)
are cancers that affect lymphocytes and are essentially the same
disease, with the only difference being the location where the cancer
primarily occurs. When most of the cancer cells are located in the
bloodstream and the bone marrow, the disease is referred to as CLL,
although the lymph nodes and spleen are often involved. When the cancer
cells are located mostly in the lymph nodes, the disease is called SLL.
The symptoms of CLL/SLL include a tender, swollen abdomen and feeling
full even after eating only a small amount. Other symptoms can include
fatigue, shortness of breath, anemia, bruising easily, night sweats,
weight loss, and frequent infections. However, many patients with
CLL/SLL will live for years without symptoms. There are approximately
200,000 patients in the US affected by CLL/SLL with nearly 20,000 new
diagnoses this year alone. While there are therapies currently
available, real-world data reveals that a significant number of patients
either relapse following treatment, become refractory to current agents,
or are unable to tolerate treatment, representing a significant medical
need. 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 CLL/SLL.

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.

Forward looking statements notice

This press release and the commentary in the conference call to be held
today each include 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 COPIKTRA,
and Verastem Oncology’s PI3K program generally, its commercialization of
COPIKTRA, the potential commercial success of COPIKTRA, including
financial guidance and patient population estimates, the anticipated
adoption of COPIKTRA 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 the risks and uncertainties,
among other things, regarding: the commercial success of COPIKTRA in the
United States; physician and patient adoption of COPIKTRA, including
those related to the safety and efficacy of COPIKTRA; the uncertainties
inherent in research and development of COPIKTRA, such as negative or
unexpected results of clinical trials; whether and when any applications
for COPIKTRA 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 COPIKTRA, 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
COPIKTRA will be commercially successful in such jurisdictions; our
ability to obtain, maintain and enforce patent and other intellectual
property protection for COPIKTRA and our 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 COPIKTRA; the fact
that regulatory authorities in the U.S. or other jurisdictions, if
approved, could withdraw approval; whether preclinical testing of our
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
our product candidates is uncertain; that third-party payors (including
government agencies) may not reimburse for COPIKTRA; that there may be
competitive developments affecting our product candidates; that data may
not be available when expected; that enrollment of clinical trials may
take longer than expected; that COPIKTRA or our 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 COPIKTRA will be ineffective
at treating patients with lymphoid malignancies; that we will be unable
to successfully initiate or complete the clinical development and
eventual commercialization of our product candidates; that the
development and commercialization of our product candidates will take
longer or cost more than planned; that we may not have sufficient cash
to fund our contemplated operations; that we, CSPC Pharmaceutical Group,
Yakult Honsha Co., Ltd. or Infinity Pharmaceuticals, Inc. will fail to
fully perform under the duvelisib license agreements; that we may be
unable to make additional draws under our debt facility or obtain
adequate financing in the future through product licensing,
co-promotional arrangements, public or private equity, debt financing or
otherwise; that we will not pursue or submit regulatory filings for our
product candidates, including for duvelisib in patients with chronic
lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) or indolent
non-Hodgkin lymphoma (iNHL) in other jurisdictions; and that our 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 March 31, 2019, as filed with the Securities and
Exchange Commission (SEC) on May 9, 2019, its Annual Report on Form 10-K
for the year ended December 31, 2018 as filed with the SEC on March 12,
2019 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.

References

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 2011;19:715-727.
4www.clinicaltrials.gov,
NCT03372057.

Contacts

Verastem Oncology:
John Doyle
Vice President, Investor
Relations & Finance
+1 781-469-1546
jdoyle@verastem.com

Investors:
Joseph Rayne
Argot Partners
+1
617-340-6075
joseph@argotpartners.com

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