CAMBRIDGE, Mass., Nov. 9, 2020 /PRNewswire/ -- Leap
Therapeutics, Inc. (Nasdaq: LPTX), a biotechnology company focused
on developing targeted and immuno-oncology therapeutics, today
announced the presentation of clinical data from its Phase
1b/2a clinical trial of DKN-01 in
patients with advanced esophagogastric cancer (EGC) at the Society
for Immunotherapy of Cancer's 35th Anniversary Annual
Meeting. DKN-01 is a humanized monoclonal antibody that binds to
and blocks the activity of the Dickkopf-1 (DKK1) protein.
In the study, high levels of tumoral DKK1 expression correlated with improved clinical
outcomes in heterogeneous EGC patients treated with DKN-01 as
monotherapy or in combination with pembrolizumab or paclitaxel.
Pooled data for the 69 patients in the study for whom tumoral
DKK1 expression data is available
demonstrated that DKK1-high patients
experienced higher overall response rates (ORR), a doubling of
median progression-free survival (PFS), and longer median overall
survival (OS) as compared to DKK1-low
patients. Additionally, DKK1-high
anti-PD-1/PD-L1 refractory patients treated with DKN-01 plus
pembrolizumab experienced longer PFS and OS compared to
DKK1-low patients, suggesting that
DKK1 tumoral expression may serve as
a predictive biomarker to identify patients for treatment with
DKN-01 in combination with anti-PD-1 antibodies. No notable
differences were found in baseline MSS, TMB, or PD-L1 expression
between DKK1-high versus DKK1-low groups.
"We continue to observe clinically meaningful activity of DKN-01
in patients with advanced previously treated esophagogastric cancer
that reinforces our belief that elevated tumoral DKK1 expression is a predictive biomarker for
improved outcomes, particularly for those patients treated with
DKN-01 in combination with an anti-PD-1 antibody," said
Samuel J. Klempner, MD, Assistant
Professor, Massachusetts General Hospital Cancer
Center and Harvard Medical School.
"We believe that the totality of the results from this study
provides strong support for the ongoing study of DKN-01 in
combination with tislelizumab, an anti-PD-1 antibody, in
DKK1-high second line
gastroesophageal junction and gastric cancer (GEJ/GC) patients and
in combination with tislelizumab, capecitabine, and oxaliplatin in
first-line GEJ/GC patients," continued Dr. Klempner.
The P102 Study in Relapsed or Refractory Esophagogastric
Cancer
The P102 study (KEYNOTE-731) is a multi-part Phase 1/2 study of
DKN-01 as a monotherapy and in combination with paclitaxel or
KEYTRUDA® (pembrolizumab) in advanced EGC patients, with a median
of two previous treatments with standard therapies, representing a
difficult to treat population. The study is intended to establish
the safety and activity of DKN-01 as a monotherapy and in
combination with paclitaxel or pembrolizumab, with efficacy
endpoints of ORR, PFS, and OS. Tumoral DKK1 expression was determined retrospectively by
RNAscope® chromogenic in situ hybridization and correlated
with clinical outcomes. Pembrolizumab was provided for the study
through a clinical trial collaboration agreement with Merck (known
as MSD outside the United States
and Canada).
Key DKN-01/Pembrolizumab Findings from the P102 Study
- Anti-PD-1/PD-L1 refractory patients (all):
The four DKK1-high patients had
a significantly longer PFS of 12.8 weeks and OS of 46 weeks as
compared to the five DKK1-low
patients who experienced PFS of 6 weeks and OS of 16
weeks.
- Anti-PD1/PD-L1 refractory GEJ/GC patients:
The three DKK1-high patients
had a best response of stable disease (SD) and a longer PFS of 13.4
weeks and OS of 37.4 weeks, as compared to the two DKK1-low patients who both had progressive
disease (PD) with a PFS of 3.6 weeks and OS of 11.7 weeks.
- Anti-PD-1/PD-L1 naïve GEJ/GC patients: As
previously reported, DKK1-high
patients experienced over 22 weeks PFS and nearly 32 weeks OS, with
a 50% overall response rate and 80% disease control rate (DCR) in
ten evaluable patients. DKK1-low
patients experienced nearly 6 weeks PFS and over 17 weeks OS, with
a 20% DCR in fifteen evaluable patients. PD-L1 Combined Positive
Scores (CPS) did not predict efficacy on the combination of DKN-01
plus pembrolizumab. In multi-variate analysis, DKK1-high status correlated with longer PFS
independent of PD-L1 CPS scores.
About DKN-01
DKN-01 is a humanized monoclonal antibody
that binds to and blocks the activity of the Dickkopf-1
(DKK1) protein, a modulator of
Wnt/Beta-catenin signaling, a signaling pathway frequently
implicated in tumorigenesis and suppressing the immune system.
DKK1 has an important role in tumor
cell signaling and in mediating an immuno-suppressive tumor
microenvironment through enhancing the activity of myeloid-derived
suppressor cells and downregulating NK ligands on tumor
cells. The U.S. Food and Drug Administration has granted
Orphan Drug Designation for the treatment of gastric and
gastroesophageal junction cancer and Fast Track Designation in
combination with tislelizumab for the treatment of patients with
gastric and gastroesophageal junction adenocarcinoma whose tumors
express high DKK1 protein, following
disease progression on or after prior fluoropyrimidine- and
platinum- containing chemotherapy and if appropriate, human
epidermal receptor growth factor (HER2)/neu-targeted therapy.
About Leap Therapeutics
Leap Therapeutics
(Nasdaq:LPTX) is focused on developing targeted and immuno-oncology
therapeutics. Leap's most advanced clinical candidate, DKN-01, is a
humanized monoclonal antibody targeting the Dickkopf-1 (DKK1) protein, a Wnt pathway modulator. DKN-01
is in clinical trials in patients with esophagogastric,
hepatobiliary, gynecologic, and prostate cancers. Leap has formed a
strategic partnership with BeiGene, Ltd. for the rights to develop
DKN-01 in Asia (excluding
Japan), Australia, and New
Zealand. For more information about Leap Therapeutics, visit
http://www.leaptx.com or our public filings with the SEC that are
available via EDGAR at http://www.sec.gov or via
https://investors.leaptx.com/ .
FORWARD-LOOKING STATEMENTS
This press release contains forward-looking statements within
the meaning of Section 27A of the Securities Act of 1933, Section
21E of the Securities Exchange Act of 1934 and the Private
Securities Litigation Reform Act of 1995, which involve risks and
uncertainties. These statements include statements regarding
expectations with respect to the development and advancement of
DKN-01, including the initiation, timing and design of future
studies, enrollment in future studies, potential for the receipt of
future option exercise, milestones or royalty payments from
BeiGene, and other future expectations, plans and prospects.
Although Leap believes that the expectations reflected in such
forward-looking statements are reasonable as of the date made,
forward-looking statements are subject to known and unknown risks,
uncertainties and other factors that could cause actual results to
differ materially from our expectations. Such risks and
uncertainties include, but are not limited to: that the initiation,
conduct, and completion of clinical trials, laboratory operations,
manufacturing campaigns, and other studies may be delayed,
adversely affected, or impacted by COVID-19 related issues, the
accuracy of our estimates regarding expenses, future revenues,
capital requirements and needs for financing; the outcome, cost,
and timing of our product development activities and clinical
trials; the uncertain clinical development process, including the
risk that clinical trials may not have an effective design or
generate positive results; our ability to obtain and maintain
regulatory approval of our drug product candidates; the size and
growth potential of the markets for our drug product candidates;
our ability to continue obtaining and maintaining intellectual
property protection for our drug product candidates; and other
risks. Detailed information regarding factors that may cause actual
results to differ materially will be included in Leap Therapeutics'
periodic filings with the SEC, including Leap's Annual Report on
Form 10-K for the fiscal year ended December
31, 2019, as filed with the SEC on March 16, 2020. Any forward-looking statements
contained in this release speak only as of its date. We undertake
no obligation to update any forward-looking statements contained in
this release to reflect events or circumstances occurring after its
date or to reflect the occurrence of unanticipated events.
KEYTRUDA® is a registered trademark of Merck Sharp
& Dohme Corp., a subsidiary of Merck & Co., Inc.,
Kenilworth, NJ, USA.
RNAscope® is a registered trademark of Advanced Cell
Diagnostics, Inc., Newark, CA,
USA.
CONTACT:
Douglas E. Onsi
President and CEO
Leap Therapeutics, Inc.
617-714-0360
donsi@leaptx.com
Heather Savelle
Investor Relations
Argot Partners
212-600-1902
heather@argotpartners.com
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