— Phase 1b/2 Trial Will
Investigate Mezigdomide in Combination
with Selinexor in Patients with
Relapsed/Refractory Multiple Myeloma Progressing after
T-cell Immunotherapies –
— Expected to be Initiated 1H 2024 –
NEWTON,
Mass., Oct. 30, 2023 /PRNewswire/ -- Karyopharm
Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical
company pioneering novel cancer therapies, today announced that it
has entered into a clinical trial collaboration and supply
agreement with Bristol-Myers Squibb
(NYSE: BMY) to evaluate the company's proprietary investigational
cereblon E3 ligase modulator (CELMoD™) agent mezigdomide in
combination with Karyopharm's selinexor, an approved first-in-class
inhibitor of Exportin 1 (XPO1), plus dexamethasone in patients with
relapsed/refractory multiple myeloma.
This trial will evaluate mezigdomide in combination with
selinexor doses of either 40mg or 60mg plus dexamethasone in
patients who have prior exposure to immunomodulatory
(IMiD®) drug agents, proteasome inhibitors, and
anti-CD38 monoclonal antibody treatment. All patients must have
received at least two prior lines of therapy, and either have
progressed after or are not eligible to receive CAR-T or bispecific
antibody treatment.
"This is an important collaboration with Bristol Myers Squibb to
explore this novel and entirely oral combination in patients who
have progressed following T-cell engaging therapy. This trial will
also evaluate mezigdomide-selinexor plus dexamethasone in patients
with relapsed/refractory multiple myeloma who need an effective
alternative to T-cell therapies," said Richard Paulson, MBA, President and Chief
Executive Officer of Karyopharm. "Pre-clinical studies with
selinexor and mezigdomide post T-cell mediated therapies provide
a scientific rationale for this novel combination to
potentially prevent/reverse T-cell exhaustion and improve outcomes
for more of these patients. We look forward to initiating the trial
in the first half of 2024."
"Despite multiple treatment advances, there is a growing need
for new combinations, particularly those that are all-oral,
accessible and that have novel mechanisms to help treat patients
with relapsed and refractory multiple myeloma," said Paul Richardson, M.D., the RJ Corman Professor
of Medicine, Dana Farber Cancer Institute, and senior investigator
of the study. "Pre-clinical data suggests the combination of a
selective inhibitor of nuclear export (SINE), such as selinexor,
with potent cereblon E3 ligase modulators , such as mezigdomide,
may spare T-cell function while showing potential activity against
resistant myeloma. This particular combination represents an
innovative and promising approach to treating relapsed and
refractory multiple myeloma with the convenience of an all-oral
approach. We look forward to learning more about its potential in
triple-class exposed patients, as well as in those who've
experienced [anti-]BCMA and T-cell directed treatment failure."
The primary endpoints of this trial are to assess the objective
response rate (ORR) and the clinical benefit rate (CBR). Key
secondary endpoints include progression-free survival (PFS),
overall survival (OS) and duration of response (DOR). In addition,
the trial will evaluate dynamic changes in T-cell populations and
activity as patients undergo treatment. Under the terms of the
agreement with Bristol Myers Squibb, Karyopharm will sponsor the
trial as a new arm of Karyopharm's Phase 1b/2 STOMP trial and Bristol Myers Squibb will
supply the study's clinical drug mezigdomide.
About XPOVIO® (selinexor)
XPOVIO is a first-in-class, oral exportin 1 (XPO1) inhibitor and
the first of Karyopharm's Selective Inhibitor of Nuclear Export
(SINE) compounds to be approved for the treatment of cancer. XPOVIO
functions by selectively binding to and inhibiting the nuclear
export protein XPO1. XPOVIO is approved in the U.S. and marketed by
Karyopharm in multiple oncology indications, including: (i) in
combination with Velcade® (bortezomib) and dexamethasone
(XVd) in patients with multiple myeloma after at least one prior
therapy; (ii) in combination with dexamethasone in patients with
heavily pre-treated multiple myeloma; and (iii) in patients with
diffuse large B-cell lymphoma (DLBCL), including DLBCL arising from
follicular lymphoma, after at least two lines of systemic therapy.
XPOVIO (also known as NEXPOVIO® in certain countries)
has received regulatory approvals in various indications in a
growing number of ex-U.S. territories and countries, including but
not limited to the European Union, the United Kingdom, China, South
Korea, Canada, Israel and Taiwan. XPOVIO and NEXPOVIO is marketed by
Karyopharm's partners, Antengene, Menarini, Neopharm and FORUS, in
China, South Korea, Singapore, Australia, Hong
Kong, Germany, Austria, Israel and Canada.
Please refer to the local Prescribing Information for full
details.
Selinexor is also being investigated in several other mid- and
late-stage clinical trials across multiple high unmet need cancer
indications, including in endometrial cancer and myelofibrosis.
For more information about Karyopharm's products or clinical
trials, please contact the Medical Information department at:
Tel: +1 (888) 209-9326
Email: medicalinformation@karyopharm.com
SELECT IMPORTANT SAFETY INFORMATION
Warnings and
Precautions
- Thrombocytopenia: Monitor platelet counts throughout treatment.
Manage with dose interruption and/or reduction and supportive
care.
- Neutropenia: Monitor neutrophil counts throughout treatment.
Manage with dose interruption and/or reduction and granulocyte
colony–stimulating factors.
- Gastrointestinal Toxicity: Nausea, vomiting, diarrhea,
anorexia, and weight loss may occur. Provide antiemetic
prophylaxis. Manage with dose interruption and/or reduction,
antiemetics, and supportive care.
- Hyponatremia: Monitor serum sodium levels throughout treatment.
Correct for concurrent hyperglycemia and high serum paraprotein
levels. Manage with dose interruption, reduction, or
discontinuation, and supportive care.
- Serious Infection: Monitor for infection and treat
promptly.
- Neurological Toxicity: Advise patients to refrain from driving
and engaging in hazardous occupations or activities until
neurological toxicity resolves. Optimize hydration status and
concomitant medications to avoid dizziness or mental status
changes.
- Embryo–Fetal Toxicity: Can cause fetal harm. Advise females of
reproductive potential and males with a female partner of
reproductive potential, of the potential risk to a fetus and use of
effective contraception.
- Cataract: Cataracts may develop or progress. Treatment of
cataracts usually requires surgical removal of the cataract.
Adverse Reactions
- The most common adverse reactions (≥20%) in patients with
multiple myeloma who receive XVd are fatigue, nausea, decreased
appetite, diarrhea, peripheral neuropathy, upper respiratory tract
infection, decreased weight, cataract and vomiting. Grade 3–4
laboratory abnormalities (≥10%) are thrombocytopenia, lymphopenia,
hypophosphatemia, anemia, hyponatremia and neutropenia. In the
BOSTON trial, fatal adverse
reactions occurred in 6% of patients within 30 days of last
treatment. Serious adverse reactions occurred in 52% of patients.
Treatment discontinuation rate due to adverse reactions was
19%.
- The most common adverse reactions (≥20%) in patients with
multiple myeloma who receive Xd are thrombocytopenia, fatigue,
nausea, anemia, decreased appetite, decreased weight, diarrhea,
vomiting, hyponatremia, neutropenia, leukopenia, constipation,
dyspnea and upper respiratory tract infection. In the STORM trial,
fatal adverse reactions occurred in 9% of patients. Serious adverse
reactions occurred in 58% of patients. Treatment discontinuation
rate due to adverse reactions was 27%.
- The most common adverse reactions (incidence ≥20%) in patients
with DLBCL, excluding laboratory abnormalities, are fatigue,
nausea, diarrhea, appetite decrease, weight decrease, constipation,
vomiting, and pyrexia. Grade 3–4 laboratory abnormalities (≥15%)
are thrombocytopenia, lymphopenia, neutropenia, anemia, and
hyponatremia. In the SADAL trial, fatal adverse reactions occurred
in 3.7% of patients within 30 days, and 5% of patients within 60
days of last treatment; the most frequent fatal adverse reactions
was infection (4.5% of patients). Serious adverse reactions
occurred in 46% of patients; the most frequent serious adverse
reaction was infection (21% of patients). Discontinuation due to
adverse reactions occurred in 17% of patients.
Use In Specific Populations
Lactation: Advise not to
breastfeed.
For additional product information, including full prescribing
information, please visit www.XPOVIO.com.
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.
About Mezigdomide
Cereblon E3 ligase modulators (CELMoD™) are a class of oral
immunomodulatory therapeutics that are designed to stimulate the
immune system and directly kill cancer cells by inducing the
degradation of tumor-promoting proteins. Bristol Myers Squibb is investigating a novel
CELMoD™ agent, mezigdomide, for multiple myeloma that was
intentionally designed to improve upon the demonstrated efficacy of
the IMiD agents, along with manageable tolerability, ease of
administration, and the potential to improve patient outcomes.
Mezigdomide co-opts cereblon to rapidly induce degradation of
target proteins Ikaros and Aiolos, thus inhibiting tumor cell
proliferation, promoting tumor cell death, and inducing
immune-stimulatory effects.
About Karyopharm Therapeutics
Karyopharm Therapeutics Inc. (Nasdaq: KPTI) is a
commercial-stage pharmaceutical company pioneering novel cancer
therapies. Since its founding, Karyopharm has been an industry
leader in oral Selective Inhibitor of Nuclear Export (SINE)
compound technology, which was developed to address a fundamental
mechanism of oncogenesis: nuclear export dysregulation.
Karyopharm's lead SINE compound and first-in-class, oral exportin 1
(XPO1) inhibitor, XPOVIO® (selinexor), is approved in
the U.S. and marketed by the Company in three oncology indications
and has received regulatory approvals in various indications in a
growing number of ex-U.S. territories and countries, including
Europe and the United Kingdom (as NEXPOVIO®) and
China. Karyopharm has a focused
pipeline targeting multiple high unmet need cancer indications,
including in multiple myeloma, endometrial cancer, myelodysplastic
neoplasms and myelofibrosis. For more information about our people,
science and pipeline, please visit www.karyopharm.com, and follow
us on Twitter at @Karyopharm and LinkedIn.
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 ability of selinexor to
treat patients with multiple myeloma, endometrial cancer and
myelofibrosis; the benefits and results that may be achieved
through the collaboration with BMS; and expectations related to the
clinical development of selinexor and potential regulatory
submissions of selinexor. 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 or that any of
Karyopharm's drug candidates, including selinexor and eltanexor,
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 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 obtain and 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 enroll patients in its clinical trials;
unplanned cash requirements and expenditures; development or
regulatory approval of drug candidates by Karyopharm's competitors
for products or product candidates in which Karyopharm is currently
commercializing or developing; the direct or indirect impact of the
COVID-19 pandemic or any future pandemic on Karyopharm's business,
results of operations and financial condition; and Karyopharm's
ability to obtain, maintain and enforce patent and other
intellectual property protection for any of its products or product
candidates. 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, 2023, which was filed with the
Securities and Exchange Commission (SEC) on August 2, 2023,
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.
XPOVIO® and NEXPOVIO® are
registered trademarks of Karyopharm Therapeutics Inc. Any other
trademarks referred to in this release are the property of their
respective owners.
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