Objective Response Rate Increases to 33.3%
Overall and is 35% in Patients with “Double- or Triple-Hit”
DLBCL
Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage
pharmaceutical company, today reported updated clinical data from
the ongoing Phase 2b
Selinexor
Against
Diffuse
Aggressive
Lymphoma (SADAL) study
evaluating lead product candidate, selinexor (KPT-330), an oral
Selective Inhibitor of Nuclear Export / SINE™ compound, in patients
with relapsed or refractory diffuse large B-cell lymphoma
(DLBCL). The data will be featured in an oral presentation at
the 22nd Congress of the European Hematology Association (EHA)
taking place June 22-25, 2017 in Madrid, Spain. In the SADAL
study, selinexor has achieved a 33.3% overall response rate (ORR)
in patients with relapsed or refractory DLBCL after at least two
prior multi-agent therapies and who are ineligible for
transplantation. The observed responses continue to be
durable, with a median duration of response (DOR) of greater than 7
months, including prolonged complete responses (CRs).
Updated Phase 2b SADAL Data in Relapsed
or Refractory DLBCL
In the oral presentation, titled “Single Agent
Oral Selinexor Exhibits Durable Responses in Relapsed/Refractory
Diffuse Large B-Cell Lymphoma (DLBCL) of Both GCB and Non-GCB
Subtypes: The Phase 2b SADAL Study,” Marie Maerevoet, MD, Institute
Jules Bordet in Belgium, will present the updated Phase 2b SADAL
data. Per the SADAL study protocol, the updated efficacy data
were restricted to the interim analysis cohort (n=63), which were
previously reported at AACR 2017, and the updated safety results
include updated data on all patients that received at least one
dose of selinexor as of the data cutoff date.
Dr. Maerevoet commented, “We are highly
encouraged by the impressive response rates that continue to be
observed with single-agent oral selinexor in these heavily
pretreated patients with DLBCL who have received two or more prior
therapies and are not eligible for transplantation, and for whom no
standard therapy exists. Along with being clinically active
and durable, including prolonged complete responses, the 60mg dose
continues to be well tolerated with a low incidence of Grade 3 or
greater adverse events, which were manageable with dose
modifications and standard supportive care.”
A summary of the efficacy data to be
presented at EHA 2017 is outlined in the following table and
described below.
Best Responses* in Patients as of 15 May
2017
Category |
N |
ORR (%) |
CR (%) |
PR (%) |
SD (%) |
PD/NE (%) |
All patients |
63 |
21 (33.3%) |
9 (14.3%) |
12 (19.0%) |
6 (9.5%) |
36 (57.1%) |
|
|
|
|
|
|
|
60 mg |
32 |
11 (34.4%) |
4 (12.5%) |
7 (21.9%) |
1 (3.1%) |
20 (62.5%) |
100 mg |
31 |
10 (32.2%) |
5 (16.1%) |
5 (16.1%) |
5 (16.1%) |
16 (51.6%) |
|
|
|
|
|
|
|
GCB-Subtype |
32 |
9 (28.1%) |
4 (12.5%) |
5 (15.6%) |
3 (9.4%) |
20 (62.5%) |
Non-GCB-Subtype |
31 |
12 (38.7%) |
5 (16.1%) |
7 (22.6%) |
3 (9.7%) |
16 (51.6%) |
*Responses were adjudicated according to the
Lugano Classification (Cheson, 2014) by an independent central
radiological review committee. ORR=Overall Response Rate (CR+PR),
DCR=Disease Control Rate (CR+PR+SD), CR=Complete Response,
PR=Partial Response, SD=Stable Disease, PD=Progressive Disease,
NE=Not Evaluable for Response. Responses are based on interim
unaudited data for the first 63 patients (of 90 total patients
enrolled as of the data cutoff date).
Based on the modified intention-to-treat
analysis of the first 63 patients (median of 3 prior treatment
regimens (range 2-5)), as adjudicated by an independent central
radiological committee, 21 patients responded (9 patients with a CR
and 12 patients with a PR) for an ORR 33.3%. An additional 6
patients experienced SD, for a disease control rate of 42.9%.
The median DOR across all patients was greater than 7 months
and responses tended to occur rapidly with a median of 2 months to
onset. Among patients who responded, the median time on
treatment was 9 months with a follow up of 12.8 months. As of
the data cutoff date, 9 patients who responded remained on
treatment, including 6 patients with a CR.
The median overall survival was 8 months for all
patients on the study, consistent with the 6-7 month published
survival data in this population, indicating that their prognosis
is extremely poor. As of the data cutoff date, median
survival for the patients with PR or CR had not been reached and is
over 9 months; the median survival for patients with SD or PD, NE
disease was 4.8 months.
Selinexor also showed robust, single-agent
activity against GCB and non-GCB subtypes of DLBCL: Of the 32
patients with DLBCL of the GCB-subtype, 9 responded (4 patients
with a CR, 5 patients with a PR) for an ORR of 28.1%. Of the
31 patients with DLBCL of the non-GCB (or ABC)-subtype, 12
responded (5 patients with a CR, 7 patients with a PR) for an ORR
of 38.7%. Finally, amongst the 14 patients with “double-” or
“triple-hit” DLBCLs, the ORR was 35%, indicating that selinexor has
clear activity in this population, which usually has a particularly
poor prognosis.
Among the 90 patients evaluated for safety as of
the data cutoff date, the most common adverse events (AEs) across
both dosing groups were fatigue (61%), nausea (51%),
thrombocytopenia (50%), anorexia (49%), vomiting (31%) and anemia
(30%), and were primarily grades 1 and 2 and were managed with dose
modifications and/or standard supportive care. As expected,
the most common grade 3 and 4 AEs in the 60mg arm were
thrombocytopenia (28%), neutropenia (17%), anemia (15%), and
fatigue (11%) and were manageable with dose modifications and/or
standard supportive care.
As previously announced, in consultation with
the U.S. Food and Drug Administration (FDA), Karyopharm has amended
the SADAL study protocol to become a single-arm study focusing
solely on single-agent selinexor dosed at 60mg twice weekly and has
eliminated the 100mg arm. The FDA has agreed that the
single-arm trial design appears appropriate for accelerated
approval in DLBCL, though eligibility for accelerated approval will
depend on the complete trial results and available therapies at the
time of regulatory action. In total, the SADAL study is
expected to enroll up to a total of 130 patients in the 60mg
single-arm cohort and Karyopharm plans to report top-line results
in the second half of 2018.
“The IRC-confirmed durable responses achieved
with single-agent oral selinexor have improved over time and
continue to demonstrate robust single-agent activity and prolonged
responses in patients with heavily pretreated DLBCL, and these
responses correlate with improved overall survival,” said Sharon
Shacham, PhD, MBA, President and Chief Scientific Officer of
Karyopharm. “We were particularly pleased to see a 35%
response rate in the double- or triple-hit subgroup, a particularly
difficult to treat patient population. The 60mg treatment arm
is enrolling on track, and we look forward to reporting top-line
data from the SADAL study in the second half of 2018.
Assuming a positive outcome, we expect to seek accelerated approval
for selinexor in DLBCL.”
Details for the Oral Presentation at EHA
2017:
Title: Single Agent Oral
Selinexor Exhibits Durable Responses in Relapsed/Refractory Diffuse
Large B-Cell Lymphoma (DLBCL) of Both GCB and Non-GCB Subtypes: The
Phase 2b SADAL StudyPresenter: Marie Maerevoet,
Institute Jules Bordet, Brussels, Belgium Abstract
code: S469Topic: Aggressive Non-Hodgkin
lymphoma — Clinical Session: Aggressive
Non-Hodgkin lymphoma —
Relapsed/refractoryLocation: Hall CDate
and Time: Saturday, June 24, 2017 from 14:45 - 17:00
CET
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 2,000 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 the Company'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, including the
timing of completion of enrollment for 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 March 31, 2017,
which was filed with the Securities and Exchange Commission (SEC)
on May 4, 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
Michelle Carroll
(212) 600-1902
michelle@argotpartners.com
Media:
Eliza Schleifstein
(917) 763-8106
eliza@argotpartners.com
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