− Data Provide Further Evidence of Tolerability
with Robust Anti-Myeloma Activity When Selinexor is Combined with
Velcade, Pomalyst, Revlimid or Darzalex –
Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage
pharmaceutical company, today announced the presentation of four
posters highlighting clinical data from the ongoing Phase 1b/2
STOMP study at the American Society of Hematology (ASH) 2017 annual
meeting held December 9-12, 2017 in Atlanta. The STOMP study
is evaluating selinexor, the Company’s lead, novel, oral SINE
compound, in combination with backbone therapies for the treatment
of patients with heavily pretreated multiple myeloma (MM).
Two of the presentations feature updated data from the STOMP
arms evaluating selinexor plus low dose dexamethasone (Sd) in
combination with either Velcade® (bortezomib) (SVd), or Pomalyst®
(pomalidomide) (SPd). The other two presentations feature new
data from the STOMP arms evaluating Sd with Revlimid®
(lenalidomide) (SRd) and with Darzalex® (daratumumab) (SDd).
“The results from the SVd arm of the Phase 1b/2
STOMP study, particularly the high response rates of 83% in the
same patient population eligible for the BOSTON study and 84% in
proteasome inhibitor (PI)-naïve or PI-relapsed patients, together
with prolonged progression-free survival (PFS), strongly support
our ongoing, pivotal Phase 3 BOSTON study,” said Sharon Shacham,
PhD, MBA, President and Chief Scientific Officer of
Karyopharm. “Overall, the four presentations continue to
highlight evidence of strong activity when oral selinexor is
combined with the currently available “backbone” myeloma therapies,
including PIs, immunomodulatory drugs (IMiDs) and anti-CD38
monoclonal antibodies. Oral selinexor continues to demonstrate an
expected and manageable tolerability profile, particularly in the
SVd regimen where the combination produced higher response rates,
paired with lower rates of peripheral neuropathy (PN), compared to
the commonly used regimen of Velcade plus dexamethasone. We
are delighted to share the results of this research with the
medical community at ASH this year.”
Selinexor in Combination with Velcade
and Low-dose Dexamethasone (SVd)
In the poster presentation titled, “Selinexor in
combination with weekly low dose bortezomib and dexamethasone (SVd)
induces a high response rate with durable responses in patients
with refractory multiple myeloma,” (Abstract #3135) Nizar Bahlis,
MD, Southern Alberta Cancer Research Institute, presented updated
clinical data from the SVd arm of the STOMP study. The study
included patients whose disease was PI naïve, exposed or
refractory, provided their disease was not refractory to Velcade as
a last therapy. In this study arm, oral selinexor was
dose-escalated in once-weekly (80 or 100mg) or twice-weekly (60 or
80mg) regimens. Velcade (1.3mg/m2 subcutaneously) was
administered once-weekly or twice-weekly. Dexamethasone (dex)
was administered orally either 40mg once-weekly or 20mg
twice-weekly. The following table is a summary of the
efficacy results:
Best Responses1 in Evaluable SVd Patients as of
15-Nov-20172 |
Category |
N3 |
ORR (%) |
CR |
VGPR |
PR4 |
Median PFS |
PI Relapsed/Naïve |
19 |
16 (84%) |
2 (11%) |
5 (26%) |
9 (47%) |
>13 months |
PI Relapse/Naïve, ≤3
Prior Treatments (BOSTON5) |
18 |
15 (83%) |
2 (11%) |
6 (33%) |
7 (39%) |
PI Refractory (Velcade, Kyprolis, Ninlaro) |
21 |
9 (43%) |
1 (5%) |
4 (19%) |
4 (19%) |
6.4 months |
All |
40 |
25 (63%) |
3 (8%) |
9 (23%) |
13 (33%) |
9.0 months |
Key: ORR=Overall Response Rate (CR+VGPR+PR), CR=Complete
Response, VGPR=Very Good Partial Response, PR=Partial Response |
1Responses were adjudicated according to the International
Myeloma Working Group criteria |
2Based on interim unaudited data |
3Two patients not evaluable for response: one death unrelated
to myeloma and one withdrawal of consent before disease follow
up |
4One unconfirmed PR |
5Patient population eligible for the ongoing Phase 3,
randomized BOSTON study evaluating SVd versus Vd |
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The majority of patients had reductions in
M-protein, including 33% with a ≥90% reduction. In the PI
Relapsed/Naïve population (N=19), the ORR was 84% and the median
PFS was >13 months with similar results in the “BOSTON”
population (N=18). This compares favorably to standard Vd regimens
(the control arm of the BOSTON study) with ORR 60-65% and PFS 7-9
months across many previous studies.
Adverse events were consistent with those
reported previously from the SVd arm of the STOMP study with
nausea, anorexia, fatigue, diarrhea and vomiting the most commonly
reported for Grade 1/2. Importantly, the reported PN across
all patients was Grade 1/2 and limited to six patients (14%), of
which five had prior Velcade exposure. Grade ≥3 adverse
events were also consistent with those reported previously with
thrombocytopenia, neutropenia, fatigue and anemia being the most
common. The recommended Phase 2 dose (RP2D) regimen for SVd
is oral selinexor (100mg once weekly), Velcade (1.3mg/m2
once-weekly subcutaneously) and oral dex (40mg once weekly), which
represents 40% less Velcade and 25% less dex compared to the
approved standard Velcade + dex (Vd) regimen.
Dr. Bahlis commented, “These updated data
continue to support the thesis that selinexor combined with
once-weekly Velcade and low-dose dex is well tolerated and highly
active in relapsed or refractory myeloma. The high response
rates and durability observed with SVd are achieved with 40% less
Velcade and 25% less dex, with no overt major organ
toxicities. The SVd response rates in patients with PI
non-refractory myeloma, together with the low rate of PN, compares
favorably to the response rates and much higher PN reported from
other late-stage Vd trials. In patients with PI refractory
myeloma, the response rates reported here support prior preclinical
findings suggesting selinexor’s potential to re-sensitize myeloma
to PIs.”
Selinexor in Combination with Pomalyst
and Low-dose Dexamethasone (SPd)
In the poster presentation titled, “Selinexor in
Combination with Pomalidomide and Low Dose Dexamethasone in a
Relapsed / Refractory Multiple Myeloma Patient Population with
Prior Proteasome Inhibitor and Lenalidomide Exposure,” (Abstract
#3136) Christine Chen, MD, FRCP, University of Toronto, Princess
Margaret Cancer Center, presented updated clinical data from the
SPd arm of the STOMP study which includes MM patients who
previously received Revlimid and a PI. In this study arm,
selinexor was dosed orally either once weekly (60 or 80mg) or twice
weekly (60 or 80mg) with Pomalyst (4mg orally, once daily) and dex
(orally, 40mg once weekly or 20mg twice weekly). The
following table is a summary of the efficacy results:
Best Responses1 in Evaluable SPd Patients as of
15-Nov-20172 |
Category |
N3 |
ORR (%) |
VGPR |
PR4 |
Median PFS |
Pomalyst Naïve and Revlimid Refractory or
Relapsed |
19 |
12 (63%) |
2 (11%) |
10 (53%) |
11.6 months |
Pomalyst and Revlimid Refractory |
8 |
3 (38%) |
- |
3 (38%) |
4.8 months |
All |
27 |
15 (56%) |
2 (7%) |
13 (48%) |
11.6 months |
Key: ORR=Overall Response Rate (VGPR+PR) |
1Responses were adjudicated according to the International
Myeloma Working Group criteria |
2Based on interim unaudited data |
3Four patients not evaluable for response: one death unrelated
to myeloma, one non-compliance with study procedures, two
withdrawals of consent before disease follow up |
4One unconfirmed PR |
|
Responses tended to occur rapidly with a median
of one month to onset. Median PFS of 11.6 for SPd compares
favorably with the PFS of ~4 months reported for Pomalyst-dex in
the Revlimid refractory or relapsed population.
Among the 31 patients evaluable for safety, the
most common Grade 1/2 adverse events were nausea (52%), anorexia
(45%), fatigue (45%) and diarrhea (32%). The most common
Grade ≥3 adverse events were neutropenia (55%), thrombocytopenia
(32%) and anemia (29%). Gastrointestinal adverse events were
generally manageable with antiemetics. There were two Grade 5
treatment-related events (febrile neutropenia and intracranial
hemorrhage). Five DLTs (Grade 3 fatigue, neutropenia and
febrile neutropenia) were observed in patients receiving selinexor
60mg twice weekly and 80mg once weekly. Based on the activity
and tolerability observed in this study arm, 60-80mg of oral
selinexor 60mg once weekly are being evaluated in combination with
Pomalyst (3mg orally, once daily) and low dose dex to determine the
RP2D for this combination regimen.
Dr. Chen commented, “Myeloma patients whose
disease is refractory to a PI and an IMiD would typically move to
the currently approved regimen of Pomalyst and dex, which carries
an expected ORR of up to 30% and PFS of approximately four months
in this patient population. The 56% ORR reported here shows
the significant clinical activity of this novel, all oral, SPd
regimen in patients with heavily pretreated myeloma. These
data continue to build upon the body of clinical data suggesting
that once-weekly selinexor is generally well tolerated and can
rapidly induce durable responses when combined with Pomalyst and
dex in patients with PI- and Revlimid-exposed myeloma, including
patients whose disease was refractory to prior therapy with
Pomalyst. This SPd regimen has the potential to provide a new
therapeutic option for myeloma patients where a significant unmet
need remains.”
Selinexor in Combination with Revlimid
and Low-dose Dexamethasone (SRd)
In the poster presentation titled, “A Phase
Ib/II Trial of Selinexor Combined with Lenalidomide and Low Dose
Dexamethasone in Patients with Relapsed / Refractory Multiple
Myeloma,” (Abstract #1861) Darrell White, MD, Dalhousie University
and QEII Health Sciences Center, presented new clinical data from
the SRd arm of the STOMP study evaluating patients who received at
least one prior therapy, which may include prior Revlimid, as long
as the patient’s MM was not refractory to prior Revlimid.
Patients whose MM was refractory to Revlimid maintenance regimens
were also allowed in this cohort. In this study arm, oral
selinexor was dose-escalated starting at either 60mg once weekly or
60mg twice weekly, with Revlimid (25mg orally, once daily), and dex
(orally, 40mg once weekly or 20mg twice weekly). The
following table is a summary of the efficacy results:
Best Responses1 in Evaluable SRd Patients as of
15-Nov-20172 |
Category |
N3 |
ORR |
VGPR |
PR4 |
Revlimid Naïve (All) |
12 |
11 (92%) |
3 (25%) |
8 (67%) |
Revlimid Naïve, ≤2 Prior Treatments |
10 |
10 (100%) |
3 (30%) |
7 (70%) |
Revlimid Relapsed or Refractory |
4 |
2 (50%) |
- |
2 (50%) |
All |
16 |
13 (81%) |
3 (19%) |
10 (63%) |
Key: ORR=Overall Response Rate (VGPR+PR) |
1Responses were adjudicated according to the International
Myeloma Working Group criteria |
2Based on interim unaudited data |
3Three patients not evaluable for response: two deaths
unrelated to myeloma, one withdrawal of consent before disease
follow up |
4Three unconfirmed PRs |
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Median PFS for the overall study population and
for patients with Revlimid-naïve disease was not reached. The
median time on treatment for the overall study population was not
reached.
Among the 19 patients evaluable for safety, the
most common Grade 1/2 adverse events were nausea (68%), anorexia
(42%), fatigue (42%), weight loss (42%), constipation (32%) and
vomiting (32%). The most common Grade ≥3 adverse events were
thrombocytopenia (68%) and neutropenia (58%).
Gastrointestinal adverse events were generally manageable with
antiemetics. Five DLTs (thrombocytopenia (n=4) and anorexia
(n=1)) were observed in patients receiving selinexor 60mg twice
weekly and 80mg once weekly. Thrombocytopenia and anorexia
were reduced in the selinexor 60mg once weekly cohort versus the
twice weekly groups. Based on the activity and tolerability
observed in this study arm, the RP2D of the all-oral SRd is
selinexor (60mg orally, once weekly), Revlimid (25mg orally, once
daily) and dex (40mg orally, once weekly).
Dr. White commented, “These Phase 1 results
suggest that selinexor can be safely combined with Revlimid and dex
in an all oral regimen in patients with relapsed or refractory
myeloma who have received at least one prior therapy. We were
especially pleased to see an encouraging 81% response rate across
all patients and a 92% response rate in patients with
Revlimid-naïve disease, clear signals of clinical activity, with no
new or unexpected toxicities observed. Importantly, this
combination shows no evidence of cardiac, pulmonary, liver or renal
toxicity. We look forward to continuing our evaluation of
selinexor in this SRd regimen in patients with relapsed or
refractory myeloma.”
Selinexor in Combination with Darzalex
and Low-dose Dexamethasone (SDd)
In the poster presentation titled, “A Phase 1b
Study to Assess the Combination of Selinexor and Daratumumab in
Patients with Relapsed/Refractory Multiple Myeloma Previously
Exposed to Proteasome Inhibitors (PI) and Immunomodulatory Drugs,”
(Abstract #3100) Cristina Gasparetto, MD, Duke University Cancer
Center, presented new clinical data from the SDd arm of the STOMP
study evaluating MM patients who received at least three prior
lines of therapy, including a PI and an IMiD, or patients with MM
refractory to both a PI and an IMiD. In this study arm, oral
selinexor was dose escalated using either 100mg once weekly or 60mg
twice weekly, with Darzalex (16mg/kg intravenously once weekly) and
dex (orally, 40mg once weekly or 20mg twice weekly). The
following table is a summary of the efficacy results:
Best Responses1 in Evaluable SDd Patients as of
15-Nov-20172 |
Category |
N3 |
ORR |
VGPR |
PR4 |
Darzalex Naïve |
6 |
5 (83%) |
3 (50%) |
2 (33%) |
All |
8 |
5 (63%) |
3 (38%) |
2 (25%) |
Key: ORR=Overall Response Rate (VGPR+PR) |
1Responses were adjudicated according to the International
Myeloma Working Group criteria |
2Based on interim unaudited data |
3One patient not evaluable for response withdrew consent prior
to disease follow up due to severe infusion reaction associated
with Darzalex |
4One unconfirmed PR |
|
Four of nine patients remain on treatment.
Responses tended to occur rapidly with a median of one month to
onset. Among the nine patients evaluable for safety, the most
common Grade 1/2 adverse events were fatigue (44%), nausea (33%)
and neutropenia (33%). The most common Grade 3/4 adverse
events were thrombocytopenia (56%), leukopenia (44%), anemia (44%)
and neutropenia (33%). Gastrointestinal adverse events
were generally manageable with antiemetics. The maximum
tolerated dose was not reached. Two DLTs (Grade 3
thrombocytopenia and Grade 2 fatigue) were observed in patients
receiving selinexor 60mg twice weekly; both patients showed
responses. Based on the preliminary tolerability and efficacy
data, the RP2D of SDd is selinexor (100mg orally, once weekly),
Darzalex (16mg/kg, once weekly) and dex (40mg orally, once
weekly).
“Preclinical results have shown that oral
selinexor sensitizes patients’ myeloma cells to the anti-CD38
monoclonal antibody, Darzalex,” stated Dr. Gasparetto. “These
Phase 1b data are early but encouraging, and suggest that selinexor
can be safely combined with Darzalex and low-dose dexamethasone in
patients with heavily pretreated myeloma. The responses
observed occur rapidly within a median one cycle of
treatment. We look forward to further evaluating the SDd
combination.”
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 2,200 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 a pivotal, randomized
Phase 3 study in combination with Velcade® (bortezomib) and
low-dose dexamethasone (BOSTON), in combination with low-dose
dexamethasone (STORM) and backbone therapies (STOMP), and in
diffuse large B-cell lymphoma (SADAL), and liposarcoma (SEAL),
among others. 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 Karyopharm's clinical development
priorities for selinexor. Additional 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. Such statements
are subject to numerous important factors, risks and uncertainties
that may cause actual events or results to differ materially from
Karyopharm's current expectations. For example, there can be no
guarantee that any of Karyopharm's SINE compounds, including
selinexor or eltanexor (KPT-8602), 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,
2017, which was filed with the Securities and Exchange Commission
(SEC) on November 2, 2017, 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.
Velcade® is a registered trademark of Takeda
Pharmaceutical Company Limited.Revlimid® and Pomalyst® are
registered trademarks of Celgene Corporation.Darzalex® is a
registered trademark of Janssen Biotech, Inc.
Contacts:
Investors:Kimberly Minarovich(646)
368-8014kimberly@argotpartners.com
Gus Jenkins(646) 351-1067
gus@argotpartners.com
Media:Eliza Schleifstein(917)
763-8106eliza@argotpartners.com
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