CAMBRIDGE, Mass., March 22, 2021 /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 2 clinical trial of
DKN-01 as a monotherapy and in combination with paclitaxel in
patients with advanced gynecological malignancies at the Society of
Gynecologic Oncology 2021 Annual Meeting on Women's Cancer, being
held as a virtual meeting from March 19-25,
2021. DKN-01 is a humanized monoclonal antibody that binds
to and blocks the activity of the Dickkopf-1 (DKK1) protein, leading to the activation of the
innate immune system in the tumor microenvironment and anti-tumor
activity.
"DKN-01 demonstrated objective responses, including a
monotherapy complete response continuing now for over 2 and a half
years, and durable tumor reductions as a single agent and in
combination with paclitaxel in the advanced gynecologic cancer
patients treated in the study," said Rebecca Arend, M.D., MSPH, Associate Professor,
University of Alabama at Birmingham
O'Neal Comprehensive Cancer Center. "The disease control rate and
progression-free survival were strongest in patients whose tumors
express high levels of DKK1
(DKK1-high), which is a group that
real world evidence has shown to have poorer outcomes on other
therapies."
"The activity of DKN-01 in this study was comparable to the
monotherapy data from other widely-used immuno-oncology or targeted
therapies," Dr. Arend continued.
"As DKN-01 was extremely well tolerated, additional studies of
DKN-01 as a monotherapy and in combination with anti-PD-1 antibody
therapy are warranted in endometrial cancer patients with
DKK1-high tumors."
The P204 Study in Advanced Gynecologic Cancers
The P204 study was a Phase 2 basket study evaluating DKN-01 as a
monotherapy or in combination with paclitaxel in groups composed of
epithelial endometrial cancer (EEC), epithelial ovarian cancer
(EOC), or carcinosarcoma (MMMT) patients. The primary endpoint of
the P204 study was overall response rate (ORR), and secondary
endpoints include disease control rate (DCR) and progression-free
survival (PFS). In each group, at least fifty percent (50%) of
patients were required to have specified Wnt signaling pathway
alterations, a subgroup of which (Wnt activating mutations) are
known to drive high tumoral DKK1
expression. Tumoral DKK1 expression was determined
retrospectively by RNAscope® chromogenic in
situ hybridization and correlated with clinical
outcomes.
Key Findings from the P204 Study
One hundred-eleven patients were enrolled in the study,
including 29 EEC patients in a DKN-01 monotherapy group, 24 EEC
patients in a DKN-01 plus paclitaxel group, 14 EOC patients in a
DKN-01 monotherapy group, 19 EOC patients in a DKN-01 plus
paclitaxel group, 9 MMMT patients in a DKN-01 monotherapy group,
and 16 MMMT patients in a DKN-01 plus paclitaxel group. The key
findings from the study were:
- EEC patients and patients with Wnt activating mutations
express higher levels of DKK1: EEC patients expressed higher
levels of DKK1 and had a higher
frequency of Wnt activating mutations than patients with EOC.
Within EEC, patients with endometrioid histology had higher
DKK1 expression than those with
non-endometrioid histology. Patients whose tumors had Wnt
activating mutations expressed 14.4 times higher levels of
DKK1.
- DKN-01 has enhanced activity in patients whose tumors
express high levels of DKK1:
In the group of 22 EEC patients treated with DKN-01 monotherapy for
whom DKK1 expression data was
available, patients with DKK1-high
tumors (n=7) had greater ORR (14% vs. 0%), DCR (57% vs. 7%), and
median PFS (3.0 months vs. 1.8 months [HR 0.39; 95% CI: 0.14, 1.1])
compared to patients with DKK1-low
tumors (n=15). Additionally, seven patients did not have
DKK1 expression results available, of
whom one had a complete response (14%) and five (72%) had a best
response of stable disease, including three patients with Wnt
activating mutations.
In the group of 24 EEC patients
treated with DKN-01 plus paclitaxel, 72% of whom had received three
or more prior systemic therapies, DKK1-high patients (n=11) had improved median PFS
(5.4 months vs. 1.8 months [HR 0.34; 95% CI: 0.12, 0.97]) compared
to DKK1-low patients (n=9). Four
patients did not have DKK1 expression
data available.
- Within EEC, DKN-01 activity strongest in endometrioid
histology: In the pooled group of 27 patients with
endometrioid histology for whom DKK1
expression data was available, patients with DKK1-high tumors (n=14) had greater DCR (57% vs.
15%) and median PFS (4.1 months vs. 1.8 months [HR 0.34; 95% CI:
0.14, 0.81]) than patients with DKK1-low tumors (n=13). Additionally, seven
patients with endometrioid histology did not have DKK1 expression results available, of whom one
(14%) had a complete response and five (72%) had a best response of
stable disease, including two patients with Wnt activating
mutations.
Conference Call Details
Leap will be hosting a
conference call today at 8:30 a.m. Eastern
Time with Dr. Arend and members of Leap's management team to
discuss the data. The call can be accessed by dialing (866)
589-0108 (U.S. and Canada) or
(409) 231-2048 (international). The passcode for the conference
call is 2077923. The presentation will be webcast live and may be
accessed on the Investors page of the company's website at
https://investors.leaptx.com/, where a replay of the event will
also be available for a limited time.
About DKN-01
DKN-01 is a humanized monoclonal antibody
that binds to and blocks the activity of the Dickkopf-1
(DKK1) protein. DKK1 modulates the Wnt/Beta-catenin and
PI3kinase/AKT signaling pathways, which have 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 cell ligands on tumor
cells. The U.S. Food and Drug Administration has
granted DKN-01 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. DKN-01 is
in clinical trials in patients with esophagogastric, hepatobiliary,
gynecologic, and prostate cancers. Leap has entered into 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 view our public filings with the SEC that
are available via EDGAR at http://www.sec.gov or via
https://investors.leaptx.com/.
RNAscope® is a registered trademark of Advanced Cell
Diagnostics, Inc., Newark, CA,
USA.
FORWARD-LOOKING STATEMENTS
This press release contains forward-looking statements within
the meaning of Section 27A of the Securities Act of 1933, as
amended, Section 21E of the Securities Exchange Act of 1934, as
amended, and the Private Securities Litigation Reform Act of 1995,
which involve risks and uncertainties. These statements include
Leap's 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, milestone, 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, 2020, as filed with the SEC on March 12, 2021 and as may be updated by Leap's
Quarterly Reports on Form 10-Q and the other reports Leap files
from time to time with the SEC. Any forward-looking statement
contained in this release speaks only as of its date. Leap
undertakes no obligation to update any forward-looking statement
contained in this release to reflect events or circumstances
occurring after its date or to reflect the occurrence of
unanticipated events.
CONTACT:
Douglas E. Onsi
President & Chief Executive Officer
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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