- STOMP Data Continues to Demonstrate High
Response Rates in Patients with Heavily Pretreated Multiple Myeloma
When Selinexor Is Combined with Bortezomib and Pomalidomide -
Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage
pharmaceutical company, today announced updated results from the
Phase 1b dose-escalation portion of its ongoing STOMP study showing
high response rates when selinexor (KPT-330) is combined with the
proteasome inhibitor bortezomib (Velcade®), including in patients
with multiple myeloma (MM) that was previously refractory to
proteasome inhibitors, at the American Society of Hematology (ASH)
2016 annual meeting held December 3-6, 2016 in San Diego.
Other key presentations at the meeting described clinical
data demonstrating the activity of selinexor in combination with
carfilzomib (Kyprolis®) and pomalidomide (Pomalyst®) in MM, as well
as selinexor with dexamethasone in quad- and penta-refractory MM in
the STORM trial. Selinexor is the Company’s lead, novel, oral
Selective Inhibitor of Nuclear Export (SINE™) compound, in
development for the treatment of a variety of malignancies,
including MM and acute myeloid leukemia (AML).
“Data from the STOMP study continue to show very
high response rates and good tolerability in patients with heavily
pretreated myeloma, most of whom have disease refractory to
proteasome inhibitors as well as immunomodulatory drugs,” said
Sharon Shacham, PhD, MBA, President and Chief Scientific Officer of
Karyopharm. “Overall, the body of data presented this year at ASH
builds upon the evidence of clear synergistic activity observed
when selinexor is combined with standard myeloma agents, including
proteasome inhibitors such as bortezomib or carfilzomib and
immunomodulatory agents such as pomalidomide. Looking ahead,
our efforts remain focused on executing the STORM trial expansion,
which is evaluating selinexor in patients with penta-refractory
myeloma, and on commencing our planned pivotal Phase 3 BOSTON study
in early 2017, which will evaluate selinexor in combination with
bortezomib and dexamethasone in patients with MM previously treated
with one to three treatment regimens.”
Updated Phase 1b STOMP Clinical Data in
Relapsed or Refractory Multiple Myeloma
In an oral presentation titled, “Selinexor in
Combination with Bortezomib and Dexamethasone Demonstrates
Significant Activity in Patients with Refractory Multiple Myeloma
Including Proteasome-Inhibitor Refractory Patients,” Nizar Bahlis,
MD, Assistant Professor of Hematology, Southern Alberta Cancer
Research Institute, presented updated clinical data from the
selinexor + Velcade (bortezomib) + dexamethasone (SVd) arm of the
ongoing Phase 1b/2 STOMP study in patients with heavily pretreated
relapsed/refractory MM.
A summary of data from all 22 patients in the
dose-escalation cohorts receiving selinexor in combination with
Velcade and dexamethasone treated as of November 30, 2016 is
outlined in the following table and described below. The patients
in this cohort were heavily pretreated and the majority (68%) had
MM refractory to the proteasome inhibitors bortezomib and/or
carfilzomib. Selinexor was given once or twice weekly, and 19 of
the 22 patients received once weekly Velcade subcutaneously as
initial treatment; three patients initially received twice weekly
Velcade but this was reduced to once weekly after one cycle. All 22
patients were evaluable for response and 11 patients were
continuing on study as of the data cutoff date.
Phase 1b STOMP Study (Selinexor + Velcade
(Bortezomib) + Dexamethasone Arm) as of 30-Nov-2016 |
Prior PI Status |
N |
ORR (%) |
CBR (%) |
sCR (%) |
CR (%) |
VGPR (%) |
PR (%) |
MR (%) |
SD (%) |
PD (%) |
Refractory(7 Bortezomib, 3 Carfilzomib, 2
Ixazomib) |
15 |
10 (67%) |
13 (87%) |
1 (7%) |
1 (7%) |
2 (13%) |
6 (40%) |
3 (20%) |
1 (7%) |
1 (7%) |
Not Refractory (Exposed or
Naïve) |
7 |
7 (100%) |
7 (100%) |
-- |
1 (14%) |
2 (29%) |
4 (57%) |
-- |
-- |
-- |
All |
22 |
17 (77%) |
20 (91%) |
1 (5%) |
2 (9%) |
4 (18%) |
10 (45%) |
3 (14%) |
1 (5%) |
1 (5%) |
ORR=Overall Response
Rate (sCR+CR+VGPR+PR), CBR=Clinical Benefit Rate
(sCR+CR+VGPR+PR+MR), sCR=Stringent Complete Response, CR=Complete
Response,VGPR=Very Good Partial Response, PR=Partial Response,
R=Minor Response, SD=Stable Disease, PD=Progressive Disease |
Of the 22 patients enrolled in the SVd
combination arm (median of four prior treatment regimens (range
1-11)), 17 responded (1 patient with a stringent complete response
(sCR), 2 patients with a complete response (CR), 4 patients with a
very good partial response (VGPR) and 10 patients with a partial
response (PR)) for an overall response rate (ORR) of 77%. An
additional 3 patients experienced a minor response (MR), for a
clinical benefit rate (CBR) of 91%. Only 1 patient had progressive
disease. All 7 patients whose disease was not refractory to a PI
responded (1 patient with a CR, 2 patients with a VGPR and 4
patients with a PR) for an ORR and CBR of 100%. Fifteen of the 22
patients in the SVd combination arm had MM previously refractory to
a proteasome inhibitor and 9 patients had high-risk cytogenetics
including deletion of chromosome 17p. Ten of these 15 patients
responded (1 patient with a sCR, 1 CR, 2 VGPR and 6 PR) for an ORR
of 67%. Three additional patients achieved an MR for a CBR of 87%
in this subgroup with PI-refractory disease. Median duration of
response (DOR) was 7.8 months.
The recommended Phase 2 dose (RP2D) regimen was
identified as selinexor (100mg once weekly), bortezomib (1.3 mg/m2
weekly given subcutaneously for 4 of 5 weeks) and dexamethasone
(40mg weekly). An additional 10 patients have been enrolled into
the expansion cohort at the RP2D. Although early (median of two
cycles), all but one of these patients is responding and
tolerability is similar to that observed in the escalation
cohort.
The most commonly reported adverse events from
the RP2D were fatigue, nausea, anorexia and vomiting, which were
primarily grade 1 and reversible. Grade 3 adverse events included
fatigue, diarrhea, thrombocytopenia and abdominal pain and each
occurred at a rate of 6% (n=1). The only Grade 4 adverse event was
thrombocytopenia and occurred at a rate of 12% (n=2).
“The response rates reported to date in the
STOMP study are very encouraging. With a 77% overall response rate
in this population and most with proteasome-inhibitor refractory
disease, the synergistic effects of selinexor in combination with
bortezomib are among the most potent reported to date,” said Dr.
Bahlis. “By contrast, the expected overall response rate for the
combination of bortezomib and dexamethasone in patients with
previously treated myeloma that is not refractory to proteasome
inhibitors is approximately 50%, and less than 10% for those with
disease refractory to proteasome inhibitors. Based on these data, I
look forward to the initiation of the pivotal Phase 3 BOSTON study
in early 2017 to further evaluate and confirm these findings.”
Additional Multiple Myeloma Data
Presented at ASH 2016
The following is a summary of other key MM
abstracts that were presented at ASH on December 4 and 5, 2016:
Poster Title: Selinexor
Shows Synergy in Combination with Pomalidomide and Low Dose
Dexamethasone in Patients with Relapsed / Refractory Multiple
MyelomaPresenter: Christine Chen, Princess
Margaret Hospital, Toronto, ONPublication
ID: 3330Date and Time:
Sunday, December 4, 2016; 6:00-8:00 p.m.
PTSummary: In this study, selinexor demonstrates
impressive activity in combination with pomalidomide (Pomalyst®) in
patients with MM that is refractory to one or more PIs and/or
lenalidomide. Of the 15 evaluable patients in the SPd combination
arm (median of five prior treatment regimens (range 2-9), 9
responded (3 VGPR) and 6 PR) for an ORR of 60%. An additional 2
patients achieved an MR for a CBR of 73%. Only 1 patient had
progressive disease. Five of the 15 patients had high-risk
cytogenetics including deletion of chromosome 17p. Median
progression-free survival (PFS) was 10.3 months, with a follow up
of 7.6 months. The most common adverse events were anorexia,
nausea, fatigue, and thrombocytopenia, mainly grades 1 and 2, and
were similar to selinexor or pomalidomide used separately.
Oral Presentation Title:
Final Results of Phase 1 MMRC Trial of Selinexor, Carfilzomib, and
Dexamethasone in Relapsed/Refractory
MMPresenter: Andrzej Jakubowiak, University
of ChicagoPublication ID: 973Date
and Time: Monday, December 5, 2016; 2:45 p.m.
PTSummary: This Phase 1 study, which is
sponsored by the Multiple Myeloma Research Foundation (MMRF),
evaluated the combination of selinexor and proteasome inhibitor
(PI) carfilzomib (Kyprolis®) and dexamethasone in patients with
relapsed/refractory MM (RRMM). The combination achieved a 63%
overall response rate and a 67% response rate in patients
refractory to carfilzomib, most having progressed on the
combination of carfilzomib, pomalidomide and dexamethasone as their
last line of therapy. The selinexor, carfilzomib and dexamethasone
combination appears safe and has acceptable tolerability in
patients with RRMM, with the most commonly reported adverse events
of thrombocytopenia and neutropenia, which are manageable with dose
modifications. These results provide early clinical evidence that
the addition of selinexor has the ability to overcome carfilzomib
resistance, warranting further investigation of the regimen.
Poster Title: A Phase 1/2
Study of the Second Generation Selective Inhibitor of Nuclear
Export Compound, KPT-8602, in Patients with Relapsed Refractory
MMPresenter: Frank Cornell, Vanderbilt
Ingram Cancer Center, Nashville, TNPublication
ID: 4509Date and Time:
Monday, December 5, 2016; 6:00-8:00 p.m.
PTSummary: Data from this ongoing Phase 1/2
study demonstrate that oral KPT-8602 is well-tolerated in heavily
pretreated patients with relapsed or refractory MM and shows early
signs of efficacy.
Karyopharm to Host Multiple
Myeloma-focused Dinner Reception and Webcast at ASH
2016
On Monday, December 5, 2016, Karyopharm will
host an investor and analyst dinner reception, which will feature a
moderated panel discussion with recognized experts in the treatment
of MM, updated selinexor data in MM, and a live Q&A session.
Confirmed external speakers include:
- Daniel Auclair, PhD (Moderator), Multiple Myeloma Research
Foundation
- Nizar Bahlis, MD, University of Calgary, Southern Alberta
Cancer Research Institute
- Paul G. Richardson, MD, Dana Faber Cancer Institute,
Jerome Lipper Multiple Myeloma Center
- Ravi Vij, MD, MBA, Washington University School of Medicine in
St. Louis, Oncology Division
- Dan T. Vogl, MD, Abramson Cancer Center Clinical Research
Unit, University of Pennsylvania
In addition, Michael Kauffman, MD, PhD, CEO of
Karyopharm Therapeutics, will be joining.
The event will take place during the ASH 2016
annual meeting and interested parties can access a live webcast of
the event beginning Monday, December 5, 2016 at 8:15 p.m. PT under
“Events & Presentations” in the "Investors" section of the
company's website at http://investors.karyopharm.com/events.cfm. A
replay of the webcast will be archived on the company’s website for
90 days following the event.
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 1,800 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 September 30,
2016, which was filed with the Securities and Exchange Commission
(SEC) on November 7, 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 LimitedPomalyst® is a registered trademark
of Celgene CorporationKyprolis® is a registered trademark of Onyx
Pharmaceuticals, Inc.
Contacts:
Justin Renz
(617) 658-0574
jrenz@karyopharm.com
Gina Nugent
(617) 460-3579
nugentcomm@aol.com
Media covering ASH 2016:
Eliza Schleifstein
(917) 763-8106
eliza@argotpartners.com
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