- Single-Agent Selinexor Demonstrates Robust
Clinical Benefit and Favorable Tolerability in Patients with
Heavily Pre-treated Gynecologic Cancers -
Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage
pharmaceutical company, today announced that an oral presentation
highlighting updated clinical data from the Company’s ongoing Phase
2 study of selinexor (KPT-330), its lead, novel, oral Selective
Inhibitor of Nuclear Export / SINE™ compound that inhibits exportin
1 (XPO1), for the treatment of gynecological cancers (the SIGN
study) will be presented at the European Society of Medical
Oncology (ESMO) 2016 annual meeting being held October 7-11, 2016
in Copenhagen, Denmark. Two posters featuring predictive
biomarker data supporting selinexor’s activity in gynecological and
colorectal cancers will also be presented.
In the oral presentation, titled “Results of a
Phase 2 Trial of Selinexor, an Oral Selective Inhibitor of Nuclear
Export (SINE) in 114 Patients with Gynecological Cancers,” Ignace
B. Vergote, MD, PhD, Head of the Department of Gynecologic
Oncology, Catholic University of Leuven, Belgium, and lead
investigator of the SIGN study, will describe clinical data from
the study, which includes durable anti-cancer activity in
gynecological malignancies with disease control rates up to 49% and
good tolerability.
“There is a significant need for new therapies
for patients with progressive gynecological cancers,” said Dr.
Vergote. “We are excited by the anti-tumor activity observed
in this study with single-agent oral selinexor, especially in
heavily pre-treated patients with relapsed ovarian and endometrial
cancers. Selinexor-associated adverse events were found to be
manageable with supportive care and dose modifications as
demonstrated by the number of patients who have remained on study
after achieving disease control, with some continuing treatment for
longer than 12 months. Notably, we found that ovarian cancer
patients receiving 50 mg/m2 (approximately 80 mg) of selinexor once
weekly achieved similar benefit with considerably fewer adverse
events compared to those receiving twice weekly dosing. We
look forward to further elucidating the potential of oral selinexor
in late-stage clinical trials in ovarian and endometrial
cancers.”
"The increasing body of clinical data supporting
the efficacy, safety and tolerability of single-agent selinexor for
the treatment of gynecological cancers, especially the impressive
disease control rates and partial responses observed in patients
with ovarian and endometrial cancers, is very encouraging and
clearly demonstrates the potential of this first-in-class oral
agent,” said Sharon Shacham, PhD, MBA, President and Chief
Scientific Officer of Karyopharm. “In addition to the SIGN
clinical data, the biomarker data to be presented by our
researchers and collaborators at ESMO this year continue to expand
our understanding of the underlying biological mechanisms that
drive selinexor’s anti-cancer activity. Collectively, these
data provide important insights that will help guide our future
clinical development of selinexor not only in gynecologic and
colorectal cancers, but across a wide variety of malignancies.”
A summary of data from 102 evaluable patients
treated in the SIGN study as of September 12, 2016 are outlined in
the following table and described below. Twelve patients were
non-evaluable for best response based on lack of tumor assessment
(no PET-CT scans) after baseline.
Cancer Type |
Dose |
N |
DCR (%) |
PR (%) |
Ovarian |
35mg/m2 (BIW) |
18 |
11 (61%) |
2 (11%) |
50mg/m2 (BIW) |
22 |
10 (45%) |
3 (14%) |
50mg/m2 (QW) |
19 |
8 (42%) |
3 (16%) |
All Doses |
59 |
29 (49%) |
8 (14%) |
Endometrial |
50mg/m2 (BIW) |
20 |
9 (45%) |
3 (15%) |
Cervical |
50mg/m2 (BIW) |
23 |
6 (26%) |
1 (4%) |
*Responses were adjudicated according to the Response Evaluation
Criteria in Solid Tumors (RECIST v1.1) based on interim unaudited
data. DCR=Disease Control Rate (complete response +
partial response + stable disease for at least 12 weeks)
- Of the 59 evaluable patients with ovarian cancer, 29 met the
primary endpoint (8 patients (14%) achieved a confirmed partial
response (PR) and 21 patients achieved stable disease for at least
12 weeks (SD≥12 weeks)), for a disease control rate (DCR) of
49%. Median progression free survival (PFS) for the ovarian
cancer arm was 3 months and median overall survival (OS) was 7
months.
- Of the 20 evaluable patients with endometrial cancer, 9 met the
primary endpoint (3 confirmed PRs and 6 with SD≥12 weeks), for a
DCR of 45%. Median PFS for the endometrial cancer arm was 3
months and median OS was 8 months.
- Across all arms, the most common grade 2 or 3 adverse events
were fatigue, nausea, anemia, anorexia, vomiting, weight loss and
thrombocytopenia, which were manageable with supportive care.
Notably, grade 3 adverse events were significantly reduced in
patients with ovarian cancer receiving once weekly dosing compared
to twice weekly dosing. One incidence of grade 4
thrombocytopenia without bleeding was also reported.
- For the 44 patients who met the DCR criteria, the median time
on study was 20 weeks. Fifteen patients remained on
single-agent selinexor for greater than 6 months, including 4
patients continuing on treatment for greater than 12 months.
Selinexor Biomarker Data
Two posters featuring biomarker data supporting
selinexor’s activity in gynecological and colorectal cancers will
also be presented:
- In Poster 1: “Circulating Tumor Cell Number Predicts Time to
Progression (TTP) in Patients with Heavily Pretreated Gynecological
Cancers Treated with Selinexor (SEL),” Karyopharm researchers
demonstrate the feasibility and prognostic value of identifying and
quantifying circulating tumor cells (CTCs) in the blood of patients
with gynecological cancers (ovarian, endometrial and cervical).
Based on patients from Karyopharm’s Phase 2 SIGN study, the
results of this biomarker study suggest that CTC count prior to
selinexor treatment may correlate to the length of time a patient
remains on study; patients with lower CTC counts at baseline
remained on study longer than those with higher counts.
Karyopharm believes this information could be useful in identifying
patients with heavily pretreated gynecological cancers who may
benefit from treatment with single-agent oral selinexor.
- In Poster 2: “RAS/AKT Pathway Mutations as Predictive
Biomarkers in Patients with Colorectal Cancer Treated with the
Exportin 1 (XPO1) Inhibitor Selinexor (SEL) — Inhibition of
Nuclear-Cytoplasmic Translocation of p27 as a Mechanism of
Anti-Tumour Activity,” Karyopharm collaborator Dr. V.Y. Heong,
National University Hospital, Singapore, describes data in which
treatment with selinexor appears to lead to longer PFS in patients
with advanced colorectal cancer (CRC) with RAS and/or AKT pathway
mutations, compared to CRC patients without these mutations. By
analyzing both pre- and post-selinexor treated CRC biopsy samples,
the researchers confirmed increased nuclear retention of p27 in the
RAS/AKT mutant tumors suggesting that p27 could be a key anti-tumor
mechanism in RAS/AKT pathway activated CRC tumors. These data
also suggest that selinexor could have enhanced activity against
colorectal and other tumors with RAS mutations, which are generally
difficult to treat with currently available agents.
More About the Phase 2 SIGN Study
Design
The Phase 2 SIGN study is an open-label clinical
trial evaluating the efficacy and safety of selinexor in patients
with heavily pre-treated gynecological cancers including ovarian,
endometrial and cervical cancer. Patients in the ovarian
cancer arm receive oral selinexor at a dose of 35 or 50 mg/m2 twice
weekly or 50 mg/m2 once weekly, while patients in the endometrial
and cervical cancer arms receive oral selinexor at a dose of 50
mg/m2 twice weekly. The primary endpoint of the study is
disease control rate (DCR, defined as complete responses (CRs),
plus partial responses (PRs), plus stable disease for at least 12
weeks (SD≥12 weeks)) assessed according to RECIST (v1.1) criteria.
A full description of the study is available at
www.clinicaltrials.gov (NCT02025985).
About Selinexor
Selinexor (KPT-330) is a first-in-class, oral
Selective Inhibitor of Nuclear Export / SINE™ compound. Selinexor
functions by binding with and inhibiting the nuclear export protein
XPO1 (also called CRM1), leading to the accumulation of tumor
suppressor proteins in the cell nucleus. This reinitiates and
amplifies their tumor suppressor function and is believed to lead
to the selective induction of apoptosis in cancer cells, while
largely sparing normal cells. To date, over 1,700 patients have
been treated with selinexor and it is currently being evaluated in
several mid- and later-phase clinical trials across multiple cancer
indications, including in multiple myeloma in combination with
low-dose dexamethasone (STORM) and backbone therapies (STOMP), and
in acute myeloid leukemia (SOPRA), diffuse large B-cell lymphoma
(SADAL), and liposarcoma (SEAL), among others. Karyopharm
plans to initiate a pivotal randomized Phase 3 study of selinexor
in combination with bortezomib (Velcade®) and low-dose
dexamethasone (BOSTON) in patients with multiple myeloma in early
2017. Additional Phase 1, Phase 2 and Phase 3 studies are
ongoing or currently planned, including multiple studies in
combination with one or more approved therapies in a variety of
tumor types to further inform the Company's clinical development
priorities for selinexor. The latest clinical trial information for
selinexor is available at www.clinicaltrials.gov.
About Karyopharm Therapeutics
Karyopharm Therapeutics Inc. (Nasdaq:KPTI) is a
clinical-stage pharmaceutical company focused on the discovery and
development of novel first-in-class drugs directed against nuclear
transport and related targets for the treatment of cancer and other
major diseases. Karyopharm's SINE™ compounds function by binding
with and inhibiting the nuclear export protein XPO1 (or CRM1).
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, which was founded by Dr. Sharon Shacham,
currently 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 the therapeutic potential of and potential clinical
development plans for Karyopharm's drug candidates, including the
timing of initiation of certain trials and of the reporting of data
from such trials. Such statements are subject to numerous important
factors, risks and uncertainties that may cause actual events or
results to differ materially from the Company's current
expectations. For example, there can be no guarantee that any of
Karyopharm's SINE™ compounds, including selinexor (KPT-330), will
successfully complete necessary preclinical and 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 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: 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; 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, 2016,
which was filed with the Securities and Exchange Commission (SEC)
on August 4, 2016, 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 Karyopharm expressly disclaims any obligation to update any
forward-looking statements, whether as a result of new information,
future events or otherwise.
Velcade® is a registered trademark of Takeda
Pharmaceutical Company Limited
Contact:
Justin Renz
(617) 658-0574
jrenz@karyopharm.com
Gina Nugent
(617) 460-3579
nugentcomm@aol.com
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