Duvelisib Achieves Overall Response Rate of 62%
in Patients with Relapsed or Refractory PTCL with Manageable Safety
Profile in Initial Phase of PRIMO Trial
Data Presented Support Potential of Duvelisib
Across Indications, Lines of Therapy and in Combination
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 the
presentation of key abstracts highlighting COPIKTRA® (duvelisib)
data at the American Society of Hematology 2019 Annual Meeting
taking place December 7-10, 2019, in Orlando.
“Given the aggressive nature of peripheral T-cell lymphoma
(PTCL) and the lack of effective therapeutic options for these
patients, we are pleased to present data from the dose optimization
phase of our PRIMO trial that demonstrated a 62% overall response
rate (ORR), as assessed by independent central review, with a
manageable safety profile consistent with previous clinical trials.
The results of the trial also identified the optimal dosing regimen
for future clinical study,” said Brian Stuglik, Chief Executive
Officer of Verastem Oncology. “The expansion phase of this
registration-directed study is well underway. Upon completion, we
plan to build upon our existing Fast Track Designation and Orphan
Drug Designation and submit a regulatory package to the U.S. FDA
with the goal of broadening the use of COPIKTRA to include
treatment of PTCL.”
Results from the Dose Optimization Portion of the Phase 2
PRIMO Study in Relapsed or Refractory PTCL
The PRIMO study is a multi-center, open-label,
registration-directed Phase 2 study evaluating duvelisib in
patients with relapsed or refractory PTCL that is expected to
enroll approximately 120 patients. In the dose optimization portion
of the study, patients were randomized to receive duvelisib 25mg
twice daily with an option for dose escalation (cohort 1) or
duvelisib 75mg twice daily continuously (cohort 2) until disease
progression or unacceptable toxicity. The primary endpoint of the
study was investigator-assessed overall response rate (ORR), and
secondary endpoints included duration of response (DOR) and
safety.
A total of 33 patients (cohort 1, n=20; cohort 2, n=13) were
treated in the dose optimization phase. Investigator-assessed ORRs
were 35% in cohort 1 and 54% in cohort 2, with complete response
(CR) rates of 25% and 31% in cohort 1 and cohort 2, respectively.
ORR, as assessed by blinded independent central review was 40% in
cohort 1 and 62% in cohort 2. Thirteen of 20 patients in cohort 1
and all patients in cohort 2 were able to complete one cycle of
therapy. Seven patients in cohort 1 discontinued therapy early due
to disease progression and/or toxicity. Most responses were
observed at the end of cycle 1 (cycle=28 days). At a median
follow-up of 21.4 weeks, the majority of responders were still in
response at the time of their last assessment. The most common (≥4
patients) Grade ≥3 adverse events (AEs) in all patients receiving
duvelisib were neutropenia, thrombocytopenia, diarrhea,
rash/maculopapular, lymphocytopenia, pneumonia and sepsis. Serious
AEs occurring in ≥2 patients were colitis, diarrhea, abdominal
pain, pyrexia, sepsis, pneumonia, hyponatremia, rash/maculopapular,
dyspnea, and respiratory failure.
Based on these efficacy and safety data, the investigators have
elected to investigate duvelisib starting at 75mg twice daily for
two cycles, followed by 25mg twice daily, during the dose expansion
portion of the study which is currently ongoing.
“In the dose optimization portion of the PRIMO study we observed
encouraging results, including complete and durable responses at
both dose levels,” said Steven Horwitz, MD, Memorial Sloan
Kettering Cancer Center, and principal investigator of Phase 2
PRIMO study. “We also identified a strategy for the expansion phase
dosing regimen starting with 75mg twice daily for two cycles to
achieve more a reliable initial tumor response, followed by 25mg
twice daily to try to maintain longer-term disease control by
mitigating the potential for later onset toxicity in these patients
with relapsed or refractory disease.”
Results from Phase 1 Study Investigating Duvelisib and
Venetoclax in Patients with Relapsed or Refractory CLL/SLL
Another key presentation at the meeting highlights new data from
an investigator-sponsored Phase 1 study exploring duvelisib in
combination with venetoclax in relapsed or refractory chronic
lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).
Duvelisib plus venetoclax demonstrated promising clinical activity,
a manageable tolerability profile, and a recommended Phase 2 dose
(RP2D) of 400mg of venetoclax was determined for this regimen.
In the study, 12 patients were enrolled and received oral
duvelisib and oral venetoclax. The primary endpoints of the study
are dose limiting toxicities (DLTs), maximum tolerated dose (MTD)
and identification of the RP2D. Secondary endpoints include
pharmacokinetics and preliminary efficacy.
Among the 12 evaluable patients, 11 achieved a response for an
ORR of 92%, including four (33%) CRs and seven (58%) partial
responses. Four patients had undetectable minimum residual disease
(uMRD) in the peripheral blood and bone marrow, including two
patients with a CR. The most common Grade 1 and 2 AEs were fatigue
(92%), hyperglycemia (83%), anemia (67%), and thrombocytopenia
(67%). The most common Grade ≥3 AEs were neutropenia (84%),
hypocalcemia (50%), and hypophosphatemia (25%). No DLTs were
observed, and the RP2D of venetoclax was identified as 400mg once
daily when given with standard dose duvelisib 25mg twice daily.
This study is now in a Phase 2 portion in CLL/SLL and Richter’s
Syndrome and is currently accruing new patients.
“Duvelisib plus venetoclax is a promising combination for
further study, as we have found early signals of robust activity
along with a manageable tolerability profile,” said Matthew S.
Davids, MD, Associate Director, Center for Chronic Lymphocytic
Leukemia at Dana-Farber Cancer Institute, and Principal
Investigator for the trial. “We are now actively accruing patients
in the Phase 2 portion of the study to evaluate the efficacy of
this combination in patients with CLL/SLL, with a separate cohort
exploring the activity of this regimen for patients with Richter’s
Syndrome, a particularly hard to treat population.”
Other poster presentations at the meeting include: an analysis
of cytogenetic and molecular markers associated with improved
outcomes in the patients who had received 1 prior therapy in the
Phase 3 DUO study and a description of the soon to be initiated
TEMPO study investigating an intermittent dosing regimen of
duvelisib in patients with indolent non-Hodgkin lymphoma.
The data from these studies continues to support the future
potential expansion of duvelisib across multiple indications and
lines of therapy.
Details for the ASH 2019 presentations are as
follows:
Poster Presentations
Title: Dose Optimization of Duvelisib in Patients with
Relapsed or Refractory Peripheral T-Cell Lymphoma from the Phase 2
PRIMO Trial: Selection of Regimen for the Dose-Expansion
Phase Lead author: Steven Horwitz, Memorial Sloan
Kettering Cancer Center Poster #: 1567
Session: 624. Hodgkin Lymphoma and T/NK Cell Lymphoma –
Clinical Studies: Poster I Date and Time: Saturday,
December 7, 2019; 5:30-7:30PM ET Location: Orange
County Convention Center, Hall B
Title: A Phase I Study of Duvelisib and Venetoclax in
Patients with Relapsed or Refractory CLL / SLL Lead
author: Jennifer Crombie, Dana-Farber Cancer Institute
Poster #: 1763 Session: 642. CLL: Therapy,
excluding Transplantation: Poster I Date and Time:
Saturday, December 7, 2019; 5:30-7:30 PM ET Location:
Orange County Convention Center, Hall B
Title: The Dual PI3K-δ/γ Inhibitor Duvelisib in
Combination with the Bcl-2 Inhibitor Venetoclax Shows Promising
Responses in Richter Syndrome-PDX Models Lead author:
Andrea Iannello, University of Turin Poster #:
2862 Session: 625. Lymphoma: Pre-Clinical—Chemotherapy
and Biologic Agents: Poster II Date and Time: Sunday,
December 8, 6:00-8:00 PM ET Location: Orange County
Convention Center, Hall B
Title: Cytogenetic and Molecular Marker Associations to
Outcomes with Duvelisib and Ofatumumab Treatment in Patients with
Relapsed or Refractory CLL/SLL in the DUO Trial Lead
author: Jennifer Brown, Dana-Farber Cancer Institute
Poster #: 4312 Session: 642. CLL: Therapy,
excluding Transplantation: Poster III Date and Time:
Monday, December 9, 2019; 6:00-8:00 PM ET Location:
Orange County Convention Center, Hall B
Publication Only Presentations
Title: Trial in Progress (TiP): A Phase 2,
Randomized, Open-Label, 2-Arm Study Comparing 2 Intermittent Dosing
Schedules of Duvelisib in Patients with Indolent Non-Hodgkin
Lymphoma (iNHL) (TEMPO) Lead author: Reem Karmali,
Lurie Cancer Center, Northwestern University Session:
623. Mantle cell, follicular, and other indolent B Cell Lymphoma –
Clinical studies
PDF copies of these poster presentations will be available
here after the meeting.
COPIKTRA is indicated in the US for the treatment of adult
patients with relapsed or refractory chronic lymphocytic leukemia
(CLL) or small lymphocytic lymphoma (SLL) after at least two prior
therapies and in relapsed or refractory follicular lymphoma (FL)
after at least two prior systemic therapies. Accelerated approved
in FL was based on overall response rate and continued approval may
be contingent upon confirmatory trials.
SELECT IMPORTANT SAFETY INFORMATION
This does not include all information needed to use COPIKTRA®
(duvelisib) safely and effectively. See full Prescribing
Information.
WARNING: FATAL AND SERIOUS
TOXICITIES: INFECTIONS, DIARRHEA OR COLITIS, CUTANEOUS REACTIONS,
and PNEUMONITIS
See full Prescribing
Information for complete boxed warning
- Fatal and/or serious infections occurred in 31% (4% fatal) 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%
(<1% fatal) of COPIKTRA-treated patients. Monitor for the
development of severe diarrhea or colitis. Withhold COPIKTRA.
- Fatal and/or serious cutaneous reactions occurred in 5% (<1%
fatal) of COPIKTRA-treated patients. Withhold COPIKTRA.
- Fatal and/or serious pneumonitis occurred in 5% (<1% fatal)
of COPIKTRA-treated patients. Monitor for pulmonary symptoms and
interstitial infiltrates. Withhold COPIKTRA.
WARNINGS AND PRECAUTIONS
- Hepatotoxicity: Monitor hepatic function.
- Neutropenia: Monitor blood counts.
- Embryo-Fetal toxicity: COPIKTRA can cause fetal harm. Advise
patients of potential risk to a fetus and to use effective
contraception.
ADVERSE REACTIONS
The most common adverse reactions (≥20%) are diarrhea or
colitis, neutropenia, rash, fatigue, pyrexia, cough, nausea, upper
respiratory infection, pneumonia, musculoskeletal pain, and
anemia.
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).
DRUG INTERACTIONS
- CYP3A inducers: Avoid co-administration with strong CYP3A
inducers.
- CYP3A inhibitors: Monitor for COPIKTRA toxicities when
co-administered with strong or moderate CYP3A inhibitors. Reduce
COPIKTRA dose to 15 mg twice daily when co-administered with strong
CYP3A4 inhibitors.
- CYP3A substrates: Monitor for signs of toxicities when
co-administering COPIKTRA with sensitive CYP3A substrates.
USE IN SPECIFIC POPULATIONS
Lactation: Advise women not to breastfeed.
Please see full Prescribing Information, including Boxed
Warning.
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 Orphan Drug Designation, 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 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 COPIKTRA, its commercialization of
COPIKTRA, the potential commercial success of COPIKTRA, 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., Sanofi 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 September 30, 2019, as filed
with the Securities and Exchange Commission (SEC) on October 30,
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.
4 www.clinicaltrials.gov, NCT03372057.
Dr. Horwitz and Dr. Davids have been compensated for consulting
services by Verastem Oncology and also receive research support
from the company.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20191207005012/en/
Investors: John Doyle Vice President, Investor Relations &
Finance +1 781-469-1546 jdoyle@verastem.com Media: Lisa Buffington
Corporate Communications +1 781-292-4205
lbuffington@verastem.com
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