NEWTON, Mass., Sept. 14, 2020 /PRNewswire/ -- Karyopharm
Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical
company pioneering novel cancer therapies, today announced that
four abstracts have been selected for poster presentation at the
European Society for Medical Oncology (ESMO) Virtual Congress 2020
taking place from September 19-21.
Three abstracts from investigator-sponsored studies will feature
clinical data related to XPOVIO (selinexor), the Company's first in
class, oral Selective Inhibitor of Nuclear Export (SINE) compound,
including: (i) combination data with pembrolizumab for the
treatment of melanoma, (ii) combination data with carboplatin and
paclitaxel for the treatment of advanced or metastatic solid
tumors, and (iii) combination data with topotecan for the treatment
of advanced or metastatic solid tumors. A fourth abstract
highlights the use of machine learning algorithms to investigate
characteristics associated with XPOVIO tolerability and
efficacy.
"We are excited to share additional clinical data from
multiple XPOVIO studies at ESMO this year, further highlighting
XPOVIO's potential application in solid tumors, an important area
for future pipeline expansion," said Sharon
Shacham, PhD, MBA, Founder, President and Chief Scientific
Officer of Karyopharm. "We are particularly encouraged by data from
the Phase 1b study of XPOVIO in
combination with pembrolizumab, which showed significant clinical
activity as frontline therapy compared to historic frontline
single-agent pembrolizumab in patients with metastatic non-uveal
melanoma. In addition, XPOVIO in combination with carboplatin and
paclitaxel conferred appreciable clinical activity with durable
objective responses, providing an opportunity for further
exploration in tumor types where carboplatin and paclitaxel
chemotherapy is used as the standard of care. The encouraging
results from these combination studies warrant further research
into the potential utility of XPOVIO in solid tumors."
Details for the ESMO poster presentations are as
follows:
Title: Phase 1b study to
evaluate the safety of selinexor (KPT-330) in combination with
pembrolizumab in patients with advanced malignancies - the melanoma
experience
Presenter: Isabella C. Glitza Oliva, MD Anderson Cancer
Center
Presentation Number: 1124P
Date: Available on demand on Thursday, September 17, 2020
Title: Selinexor in combination with carboplatin and
paclitaxel in patients with advanced or metastatic solid tumors:
Results of an open label, single-center, multi-arm phase
1b study
Presenter: Kyaw Z. Thein, MD Anderson Cancer Center
Presentation Number: 554P
Date: Available on demand on Thursday, September 17, 2020
Title: Selinexor in combination with topotecan in
patients with advanced or metastatic solid tumors: Results of an
open label, single-center, multi-arm phase 1b study
Presenter: Kyaw Z. Thein, MD Anderson Cancer Center
Presentation Number: 565P
Date: Available on demand on Thursday, September 17, 2020
Title: Machine learning models predict selinexor
tolerability and efficacy
Presenter: Yuval Artstein,
Karyopharm Therapeutics Inc.
Presentation Number: 89P
Date: Available on demand on Thursday, September 17, 2020
About XPOVIO® (selinexor)
XPOVIO is a first-in-class, oral Selective Inhibitor of Nuclear
Export (SINE) compound. XPOVIO functions by selectively binding to
and inhibiting the nuclear export protein exportin 1 (XPO1, also
called CRM1). XPOVIO blocks the nuclear export of tumor suppressor,
growth regulatory and anti-inflammatory proteins, leading to
accumulation of these proteins in the nucleus and enhancing their
anti-cancer activity in the cell. The forced nuclear retention of
these proteins can counteract a multitude of the oncogenic pathways
that, unchecked, allow cancer cells with severe DNA damage to
continue to grow and divide in an unrestrained fashion. Karyopharm
received accelerated U.S. Food and Drug Administration (FDA)
approval of XPOVIO in July 2019 in
combination with dexamethasone for the treatment of adult patients
with relapsed refractory multiple myeloma (RRMM) who have received
at least four prior therapies and whose disease is refractory to at
least two proteasome inhibitors, at least two immunomodulatory
agents, and an anti-CD38 monoclonal antibody. Karyopharm has also
submitted a Marketing Authorization Application (MAA) to the
European Medicines Agency (EMA) with a request for conditional
approval of selinexor in this same RRMM indication. Karyopharm's
supplemental New Drug Application (sNDA) requesting an expansion of
its current indication to include the treatment for patients with
multiple myeloma after at least one prior line of therapy has been
accepted for filing by the FDA. In June
2020, Karyopharm received accelerated FDA approval of XPOVIO
for its second indication in adult patients with relapsed or
refractory diffuse large B-cell lymphoma (DLBCL), not otherwise
specified, including DLBCL arising from follicular lymphoma, after
at least 2 lines of systemic therapy. Selinexor is also being
evaluated in several other mid-and later-phase clinical trials
across multiple cancer indications, including as a potential
backbone therapy in combination with approved myeloma therapies
(STOMP), in liposarcoma (SEAL) and in endometrial cancer (SIENDO),
among others. Additional Phase 1, Phase 2 and Phase 3 studies are
ongoing or currently planned, including multiple studies in
combination with approved therapies in a variety of tumor types to
further inform Karyopharm's clinical development priorities for
selinexor. Additional clinical trial information for selinexor is
available at www.clinicaltrials.gov.
IMPORTANT SAFETY INFORMATION
Thrombocytopenia: XPOVIO can cause life-threatening
thrombocytopenia, potentially leading to hemorrhage.
Thrombocytopenia was reported in patients with multiple myeloma
(MM) and developed or worsened in patients with DLBCL.
Thrombocytopenia is the leading cause of dosage modifications.
Monitor platelet counts at baseline and throughout treatment.
Monitor more frequently during the first 3 months of treatment.
Institute platelet transfusion and/or other treatments as
clinically indicated. Monitor patients for signs and symptoms of
bleeding and evaluate promptly. Interrupt, reduce dose, or
permanently discontinue based on severity of adverse reaction.
Neutropenia: XPOVIO can cause life-threatening
neutropenia, potentially increasing the risk of infection.
Neutropenia and febrile neutropenia occurred in patients with MM
and in patients with DLBCL. Obtain white blood cell counts with
differential at baseline and throughout treatment. Monitor more
frequently during the first 3 months of treatment. Monitor patients
for signs and symptoms of concomitant infection and evaluate
promptly. Consider supportive measures, including antimicrobials
and growth factors (e.g., G-CSF). Interrupt, reduce dose, or
permanently discontinue based on severity of adverse reaction
(AR).
Gastrointestinal Toxicity: XPOVIO can cause severe
gastrointestinal toxicities in patients with MM and DLBCL.
Nausea/Vomiting: Provide prophylactic antiemetics.
Administer 5-HT3 receptor antagonists and other anti-nausea agents
prior to and during treatment with XPOVIO. Interrupt, reduce dose,
or permanently discontinue based on severity of ARs. Administer
intravenous fluids to prevent dehydration and replace electrolytes
as clinically indicated.
Diarrhea: Interrupt, reduce dose, or permanently
discontinue based on severity of ARs. Provide standard
anti-diarrheal agents, administer intravenous fluids to prevent
dehydration, and replace electrolytes as clinically indicated.
Anorexia/Weight Loss: Monitor weight, nutritional
status, and volume status at baseline and throughout treatment.
Monitor more frequently during the first 3 months of treatment.
Interrupt, reduce dose, or permanently discontinue based on
severity of ARs. Provide nutritional support, fluids, and
electrolyte repletion as clinically indicated.
Hyponatremia: XPOVIO can cause severe or
life-threatening hyponatremia. Hyponatremia developed in patients
with MM and in patients with DLBCL.
Monitor sodium level at baseline and throughout treatment.
Monitor more frequently during the first 2 months of treatment.
Correct sodium levels for concurrent hyperglycemia (serum glucose
>150 mg/dL) and high serum paraprotein levels. Assess hydration
status and manage hyponatremia per clinical guidelines, including
intravenous saline and/or salt tablets as appropriate and dietary
review. Interrupt, reduce dose, or permanently discontinue based on
severity of the AR.
Serious Infection: XPOVIO can cause
serious and fatal infections. Most infections were not associated
with Grade 3 or higher neutropenia. Atypical infections reported
after taking XPOVIO include, but are not limited to, fungal
pneumonia and herpesvirus infection.
Monitor for signs and symptoms of infection, and evaluate and
treat promptly.
Neurological Toxicity: XPOVIO can cause
life-threatening neurological toxicities.
Coadministration of XPOVIO with other products that cause dizziness
or mental status changes may increase the risk of neurological
toxicity.
Advise patients to refrain from driving and engaging in
hazardous occupations or activities, such as operating heavy or
potentially dangerous machinery, until the neurological toxicity
fully resolves. Optimize hydration status, hemoglobin level, and
concomitant medications to avoid exacerbating dizziness or mental
status changes. Institute fall precautions as appropriate.
Embryo-Fetal Toxicity: XPOVIO 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 and males with a female partner
of reproductive potential to use effective contraception during
treatment with XPOVIO and for 1 week after the last dose.
ADVERSE REACTIONS
The most common adverse reactions
(ARs) in ≥20% of patients with MM are thrombocytopenia, fatigue,
nausea, anemia, decreased appetite, decreased weight, diarrhea,
vomiting, hyponatremia, neutropenia, leukopenia, constipation,
dyspnea, and upper respiratory tract infection.
The most common ARs, excluding laboratory abnormalities, in ≥20%
of patients with DLBCL are fatigue, nausea, diarrhea, appetite
decrease, weight decrease, constipation, vomiting, and pyrexia.
Grade 3-4 laboratory abnormalities in ≥15% of patients included
thrombocytopenia, lymphopenia, neutropenia, anemia, and
hyponatremia. Grade 4 laboratory abnormalities in ≥5% were
thrombocytopenia, lymphopenia, and neutropenia.
In patients with MM, fatal ARs occurred in 9% of patients.
Serious ARs occurred in 58% of patients. Treatment discontinuation
rate due to ARs was 27%. The most frequent ARs requiring permanent
discontinuation in ≥4% of patients included fatigue, nausea, and
thrombocytopenia.
In patients with DLBCL, fatal ARs occurred in 3.7% of patients
within 30 days, and 5% of patients within 60 days of last
treatment; the most frequent fatal AR was infection (4.5% of
patients). Serious ARs occurred in 46% of patients; the most
frequent serious AR was infection. Discontinuation due to ARs
occurred in 17% of patients.
USE IN SPECIFIC POPULATIONS
In MM, no overall
difference in effectiveness of XPOVIO was observed in patients
>65 years old when compared with younger patients. Patients ≥75
years old had a higher incidence of discontinuation due to an AR
than younger patients, a higher incidence of serious ARs, and a
higher incidence of fatal ARs. Clinical studies in patients with
relapsed or refractory DLBCL did not include sufficient numbers of
patients aged 65 and over to determine whether they respond
differently from younger patients.
The effect of end-stage renal disease
(CLCR <15 mL/min) or hemodialysis on XPOVIO
pharmacokinetics is unknown.
To report SUSPECTED ADVERSE REACTIONS,
contact Karyopharm Therapeutics Inc. at 1-888-209-9326 or
FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Please see XPOVIO Full Prescribing Information available
at www.XPOVIO.com.
About Karyopharm Therapeutics
Karyopharm Therapeutics Inc. (Nasdaq: KPTI) is a
commercial-stage pharmaceutical company pioneering novel cancer
therapies and dedicated to the discovery, development, and
commercialization of novel first-in-class drugs directed against
nuclear export and related targets for the treatment of cancer and
other major diseases. Karyopharm's Selective Inhibitor of Nuclear
Export (SINE) compounds function by binding with and inhibiting the
nuclear export protein XPO1 (or CRM1). Karyopharm's lead compound,
XPOVIO® (selinexor), received accelerated approval from the U.S.
Food and Drug Administration (FDA) in July
2019 in combination with dexamethasone as a treatment for
patients with heavily pretreated multiple myeloma. In June 2020, XPOVIO was approved by the FDA as a
treatment for patients with relapsed or refractory diffuse large
B-cell lymphoma. A Marketing Authorization Application for
selinexor for patients with heavily pretreated multiple myeloma is
also currently under review by the European Medicines Agency. In
addition to single-agent and combination activity against a variety
of human cancers, SINE compounds have also shown biological
activity in models of neurodegeneration, inflammation, autoimmune
disease, certain viruses and wound-healing. Karyopharm has several
investigational programs in clinical or preclinical development.
For more information, please visit www.karyopharm.com.
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
Karyopharm's beliefs regarding the ability of selinexor to treat
patients with myeloma, solid tumors and other diseases
and expectations related to future clinical development and
potential regulatory submissions of XPOVIO. Such statements
are subject to numerous important factors, risks and uncertainties,
many of which are beyond Karyopharm's control, that may cause
actual events or results to differ materially from Karyopharm's
current expectations. For example, there can be no guarantee
that Karyopharm will successfully commercialize XPOVIO; that
regulators will agree that selinexor qualifies for conditional
approval in the E.U. as a result of data from the STORM study or
confirmatory approval in the U.S. or EU based on the BOSTON study in patients with relapsed or
refractory multiple myeloma; or that any of Karyopharm's drug
candidates, including selinexor, will successfully complete
necessary clinical development phases or that development of any of
Karyopharm's drug candidates will continue. Further, there can be
no guarantee that any positive developments in the development or
commercialization of Karyopharm's drug candidate 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: the risk
that the COVID-19 pandemic could disrupt Karyopharm's business more
severely than it currently anticipates, including by negatively
impacting sales of XPOVIO, interrupting or delaying research
and development efforts, impacting the ability to procure
sufficient supply for the development and commercialization of
selinexor or other product candidates, delaying ongoing or planned
clinical trials, impeding the execution of business plans, planned
regulatory milestones and timelines, or inconveniencing patients;
the adoption of XPOVIO in the commercial marketplace, the timing
and costs involved in commercializing XPOVIO or any of Karyopharm's
drug candidates that receive regulatory approval; the ability to
retain regulatory approval of XPOVIO or any of Karyopharm's drug
candidates that receive regulatory approval; Karyopharm'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. Food and Drug Administration and other regulatory authorities,
investigational review boards at clinical trial sites and
publication review bodies, including with respect to the need for
additional clinical studies; the ability of Karyopharm or its third
party collaborators or successors in interest to fully perform
their respective obligations under the applicable agreement and the
potential future financial implications of such agreement;
Karyopharm's ability to obtain and maintain requisite regulatory
approvals and to enroll patients in its clinical trials; unplanned
cash requirements and expenditures; development of drug candidates
by Karyopharm's competitors for diseases in which Karyopharm is
currently developing its drug candidates; and Karyopharm's ability
to obtain, maintain and enforce patent and other intellectual
property protection for any drug candidates it is developing. These
and other risks are described under the caption "Risk Factors" in
Karyopharm's Quarterly Report on Form 10-Q for the quarter ended
June 30, 2020, which was filed with
the Securities and Exchange Commission (SEC) on August 4, 2020, and in other filings that
Karyopharm may make with the SEC in the future. Any forward-looking
statements contained in this press release speak only as of the
date hereof, and, except as required by law, Karyopharm expressly
disclaims any obligation to update any forward-looking statements,
whether as a result of new information, future events or
otherwise.
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