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 2
clinical trial of DKN-01 in patients with recurrent epithelial
endometrial cancers (EEC) at the AACR Virtual Special Conference on
Endometrial Cancer: New Biology Driving Research and Treatment
being held November 9-10, 2020.
DKN-01 is a humanized monoclonal antibody that binds to and blocks
the activity of the Dickkopf-1 (DKK1)
protein.
DKN-01 demonstrated single agent activity in the EEC patients
treated in the study, particularly in biomarker-selected subgroups
relating to DKK1 biology. Patients
with a Wnt signaling alteration had a higher overall response rate
(ORR), greater objective disease control rate (ODCR), and longer
median overall survival (OS) compared to patients without a Wnt
signaling alteration. Patients with Wnt activating mutations, a
subgroup of the Wnt signaling alterations, had the longest
progression-free survival (PFS) and OS of the subgroups evaluated.
Wnt activating mutations are associated with higher tumoral
DKK1 expression, and DKK1-high patients treated with DKN-01
monotherapy experienced a higher ORR and ODCR and longer PFS
compared to DKK1-low patients.
"Pathways modulated by DKK1, such
as the Wnt/Beta-catenin and PI3kinase/AKT pathways, are frequently
mutated in patients with endometrial cancer, and high levels of
DKK1 can both promote tumor growth
and create an immunosuppressive tumor microenvironment. The DKN-01
results in endometrial cancer patients with Wnt activating
mutations and high tumoral DKK1
expression continue to suggest that treatment with DKN-01 could
provide clinically meaningful benefit to patients with advanced
disease and few treatment options," said Rebecca Arend, M.D., Associate Professor,
Gynecologic Oncology Division, University of
Alabama at Birmingham, and Associate Scientist, O'Neal
Comprehensive Cancer Center.
"These DKN-01 monotherapy efficacy results are achieved with a
favorable safety profile and warrant further study of DKN-01 either
as a monotherapy or in combination in endometrial cancer patients
with Wnt activating mutations or high levels of tumor DKK1 expression," added Dr. Arend.
The P204 Study in Gynecologic Cancers
The P204 study is a Phase 2 basket study evaluating DKN-01 as a
monotherapy or in combination with paclitaxel in patients with
advanced gynecologic malignancies, including EEC, epithelial
ovarian cancer (EOC), and carcinosarcoma. Data being presented at
the AACR Virtual Special Endometrial Cancer Conference pertain to
DKN-01 as monotherapy in EEC patients. The primary endpoint of the
P204 study is ORR, and secondary endpoints include ODCR, PFS, and
OS in patients with recurrent EEC, EOC, or carcinosarcoma. Tumoral
DKK1 expression was determined
retrospectively by RNAscope® chromogenic in situ
hybridization and correlated with clinical outcomes.
Key Findings from the P204 Study
Twenty-nine EEC patients were enrolled in the DKN-01
monotherapy group, over 75% of whom had experienced three or
more prior lines of therapy. Of those patients, 26 were evaluable
for response. Three important biomarker-selected subgroups were the
focus of the data presentation:
- Patients with Wnt Signaling Alterations:
In the group of 20 patients with a Wnt signaling alteration, one
patient (5%) has an ongoing complete response, one patient (5%) had
a partial response (PR), eight patients (40%) had a best response
of stable disease (SD), and 10 patients (50%) had progressive
disease (PD), representing an ORR of 10% and a ODCR of 50%. In the
group of six patients without any Wnt signaling alterations, one
patient (16.7%) had a best response of SD and five patients (83.3%)
had PD. The patients with a Wnt signaling alteration
experienced PFS of 1.9 months and OS of 15.1 months, compared to
the patients without a Wnt signaling alteration who experienced PFS
of 1.8 months and OS of 8.4 months.
- Patients with Wnt Activating Mutations: The
nine patients with a Wnt activating mutation experienced PFS of 5.5
months and had not reached a median OS, compared to the 20 patients
without a Wnt activating mutation who experienced PFS of 1.8 months
and OS of 12.2 months.
- Patients expressing high tumor levels of DKK1: Tumoral DKK1 expression data was available for 19 EEC
patients treated with DKN-01 monotherapy. In the group of seven
patients with DKK1-high tumors, one
patient (14.3%) had a PR, three patients (42.9%) had SD, and 3
patients (42.9%) had PD, representing an ORR of 14.3% and a ODCR of
57.1%. In the group of 12 patients with DKK1-low tumors, one patient (8.3%) had SD and 11
patients (91.7%) had PD. The DKK1-high patients experienced PFS of 3.0 months,
compared to the DKK1-low patients who
experienced PFS of 1.8 months.
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.
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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