CAMBRIDGE, Mass., April 23, 2020 /PRNewswire/ -- Leap
Therapeutics, Inc. (Nasdaq: LPTX), a biotechnology company focused
on developing targeted and immuno-oncology therapeutics, today
announced updated clinical data from its ongoing Phase 2 clinical
trial of DKN-01, its anti-Dickkopf-1 (DKK1) antibody, as both a monotherapy and in
combination with paclitaxel chemotherapy in patients with advanced
gynecological malignancies. Leap will host a conference call with
Rebecca Arend, M.D., Assistant
Professor and Associate Scientist, Gynecologic Oncology Clinic, The
University of Alabama at Birmingham
School of Medicine Comprehensive Cancer Center Experimental
Therapeutics Program, today, April 23,
2020, at 8:30 A.M. EDT to
discuss the data.
"We are seeing clinically meaningful monotherapy activity of
DKN-01 in heavily pre-treated endometrial cancer and carcinosarcoma
populations, including a complete response, a partial response, and
durable tumor reductions in many patients. In combination with
paclitaxel, DKN-01 is generating durable responses and disease
control in paclitaxel-experienced patients," said Dr. Arend.
"This study also demonstrates the importance of mechanism of
action based biomarkers for DKN-01 therapy, as patients with high
tumor DKK1 expression or Wnt
activating mutations had enhanced progression-free survival and
overall survival. These biomarkers should be the foundation for
additional DKN-01 studies in endometrial and carcinosarcoma
patients, as monotherapy and in combination with other active
agents," continued Dr. Arend.
The P204 Study in Gynecologic Cancers
The P204 study is a Phase 2 basket study evaluating DKN-01 as a
monotherapy and in combination with paclitaxel in patients with
relapsed/refractory epithelial endometrial cancer (EEC), epithelial
ovarian cancer (EOC), or carcinosarcoma (also known as Malignant
Mixed Mullerian Tumor (MMMT)). As of the cut-off date of
December 30, 2019, 105 heavily
pretreated patients had been enrolled across the six groups of the
study. Approximately 67% of all patients had tumors with identified
Wnt pathway alterations, which included approximately 20% with Wnt
activating mutations. Patients with EEC and carcinosarcoma had
higher tumor DKK1 expression and a
higher percentage of Wnt activating mutations than the ovarian
cancer patients. Patients whose tumors had Wnt activating mutations
expressed 15 times higher levels of tumoral DKK1.
Key Findings from the P204 Study
- DKN-01 single agent activity
-
- Endometrial Cancer: Twenty-nine EEC patients were
enrolled in the DKN-01 monotherapy arm, over 75% of whom had
experienced three or more prior lines of therapy. Of those
patients, 26 were evaluable for response. In the 20 patients with a
Wnt signaling alteration, one patient (5%) has an ongoing complete
response, one patient (5%) had a partial response, eight patients
(40%) had a best response of stable disease, and 10 patients (50%)
had progressive disease, representing an overall response rate
(ORR) of 10% and a disease control rate (DCR) of 50%. In the group
of six patients without any Wnt signaling alterations, one patient
(16.6%) had a best response of stable disease and five patients
(83.3%) had progressive disease.
- Carcinosarcoma: Ten patients with carcinosarcoma
have been enrolled in the DKN-01 monotherapy arm, five of whom were
evaluable for response as of the data-cut off date. Two patients
(40%) had a best response of stable disease, one of which has
continued on monotherapy for nearly two years, and three patients
(60%) had progressive disease. Five patients had not reached their
first tumor assessment.
- DKN-01 plus paclitaxel combination activity
-
- Carcinosarcoma: Fifteen patients with
carcinosarcoma were enrolled in the DKN-01 plus paclitaxel arm, six
of whom were evaluable for response as of the data-cut off date.
Two patients (33%) have had a partial response, one patient (17%)
has had a best response of stable disease, and three patients (50%)
had progressive disease, representing an ORR of 33% and a DCR of
50%. Nine patients had not reached their first tumor
assessment.
- Endometrial Cancer: Twenty-five patients with
heavily pretreated EEC were enrolled in the DKN-01 plus paclitaxel
arm. All of these patients had previously received paclitaxel, 44%
had received hormonal therapies, 32% had received bevacizumab, 20%
had received immunotherapy, and 12% had received a PARP inhibitor.
Of those patients, 22 were evaluable for response. A total of 12
patients (55%) have had a best response of stable disease, and ten
patients (45%) had progressive disease.
- Monotherapy Patients with Wnt activating mutations have
longer Progression-Free Survival (PFS) and Overall Survival
(OS): In a pooled analysis of all DKN-01
monotherapy patients, patients with Wnt activating mutations have
demonstrated a longer median PFS of 168 days as compared to
patients without Wnt activating mutations with median PFS of 56
days. Median OS has not been reached in the Wnt activating mutation
group in the pooled analysis as compared to median OS of 328 days
in the non-Wnt activating mutation group.
- Monotherapy Patients with DKK1-high tumors have longer PFS and
OS: DKK1 expression as measured by
in situ hybridization RNAscope assay is currently available
for 68 of the patients on the study, 32 of whom were treated with
DKN-01 monotherapy. Seven patients (22%) were identified as having
DKK1-high tumoral expression.
Consistent with the results from Leap's study in patients with
esophagogastric cancer, patients whose tumors are DKK1-high have prolonged median PFS of 168 days
as compared to patients with tumors that are DKK1-low with median PFS of 56 days. Median OS
was 450 days in the DKK1-high group
in the pooled analysis as compared 276 days in the DKK1-low group.
Conference Call Details:
U.S. Dial-in
Number: (866) 589-0108
International Dial-in Number: (409) 231-2048
Conference ID: 1190677
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 the presentation slides and a
replay of the event will also be available for a limited time.
About Gynecological Cancers
There are numerous forms
of gynecologic cancers, but two of the most prevalent types are
cancers of the uterus or ovaries. According to the National Cancer
Institute, there are more than 61,000 patients diagnosed with
uterine cancer. There are currently very few post-surgical
treatment options for these patients, typically consisting of
chemotherapy, local radiation therapy, and hormonal agents, and
poor treatment outcomes. Patients with endometrial cancers have a
high frequency of mutations in a protein known as
beta-catenin, with alterations estimated at approximiately 30% of
cases by The Cancer Genome Atlas. These beta-catenin
mutations are often driver mutations leading to rapid disease
progression and poor outcomes. Carcinosarcoma, or Malignant Mixed
Mullerian Tumor, is a uterine cancer comprised of carcinoma and
sarcoma cells and accounts for less than five percent of all
uterine cancer. Carcinosarcoma is an aggressive tumor with poor
patient prognosis and poor response to chemotherapy.
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.
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
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.
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
View original content to download
multimedia:http://www.prnewswire.com/news-releases/leap-therapeutics-to-present-updated-data-for-dkn-01-monotherapy-and-paclitaxel-combination-in-gynecologic-cancers-301045516.html
SOURCE Leap Therapeutics, Inc.