Randomized Controlled First-Line Gastric
Cancer Trial of DKN-01 plus tislelizumab and chemotherapy in
collaboration with BeiGene
Leap to host R&D Day today at 12:00 p.m. ET
CAMBRIDGE, Mass., July 12,
2022 /PRNewswire/ -- Leap Therapeutics,
Inc. (NASDAQ: LPTX), a biotechnology company focused on
developing targeted and immuno-oncology therapeutics, and BeiGene,
Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global,
science-driven biotechnology company focused on developing
innovative and affordable medicines to improve treatment outcomes
and acc688235ess for patients worldwide, today announced the
initiation of Part C of the ongoing DisTinGuish study to evaluate
DKN-01, Leap's anti-SSEDickkopf 1 (DKK1) antibody, in combination with
tislelizumab, BeiGene's anti-PD-1 antibody, and chemotherapy
compared to a tislelizumab and chemotherapy control arm, in
patients with gastric or gastroesophageal junction cancer
(G/GEJ).
Additionally, Leap is initiating a new company-sponsored trial
of DKN-01 in combination with standard of care bevacizumab and
chemotherapy in second-line patients with colorectal cancer that is
designed to expand into a randomized study. Leap is also supporting
an investigator-initiated trial of DKN-01 plus pembrolizumab in
patients with endometrial cancer to be conducted at The
University of Texas M.D. Anderson
Cancer Center and at the University of Alabama
at Birmingham.
Leap's management team, together with key opinion leaders, will
host an R&D Day today to provide updates on the Company's
DKN-01 program including G/GEJ, colorectal cancer, endometrial
cancer, and prostate cancer.
"Since the presentation of the data for DKN-01 plus tislelizumab
and chemotherapy in first-line G/GEJ patients demonstrating
compelling overall response rates and progression-free survival,
Leap and BeiGene have been working together to create an optimal
global strategy for this unique combination therapy. We are excited
to enhance the development program and our collaboration with
BeiGene through a randomized controlled trial in first-line
patients, with a focus on those patients whose tumors express high
levels of DKK1," said Douglas E. Onsi, President and Chief Executive
Officer of Leap.
"Based on our clinical and preclinical data, Leap is committed
to developing DKN-01 aggressively in multiple indications," said
Cynthia Sirard, MD, Chief Medical
Officer of Leap. "Through a strategic review and prioritization
process, we have decided to initiate a company-sponsored study in
second-line colorectal cancer patients of DKN-01 in combination
with standard of care bevacizumab and chemotherapy. We will also
support an investigator-initiated study in endometrial cancer
patients of DKN-01 in combination with pembrolizumab, building on
previous data showing single-agent activity of DKN-01."
R&D Day:
Leap's management team will host an R&D Day today at
12:00 p.m. Eastern Time and will be
joined by key opinion leaders:
Samuel Klempner,
MD, Associate Professor at Harvard and
Massachusetts General Hospital;
Zev Wainberg, MD, Co-Director of the
GI Oncology Program at University of
California Los Angeles;
Rebecca Arend, MD, Assistant
Professor at University of Alabama at
Birmingham Comprehensive Cancer Center; and
David Wise, MD, PhD, Assistant
Professor at NYU Langone Health.
The live webcast presentation of the R&D Day can be accessed
by registering at https://edge.media-server.com/mmc/p/4zp7m6pw. A
replay of the event will be available for a limited time and may be
accessed on the Investors page of the Company's website at
https://investors.leaptx.com/
Gastric Cancer
The DisTinGuish study (NCT04363801) is a Phase 2 study of DKN-01
in combination with tislelizumab and standard of care (SOC)
chemotherapy in patients with inoperable, locally advanced, G/GEJ
adenocarcinoma. Part C of the DisTinGuish study will enroll
approximately 160 first-line, HER2-negative patients who have had
no prior therapy for unresectable locally advanced or metastatic
G/GEJ adenocarcinoma. Patients will be randomized 1:1 to study
DKN-01 in combination with tislelizumab and SOC chemotherapy,
compared to tislelizumab and SOC chemotherapy. The primary
objective of Part C is progression-free survival (PFS) in patients
whose tumors express high levels of DKK1 (DKK1-high).
Secondary objectives of Part C include PFS in all patients
regardless of DKK1 expression, as
well as overall survival (OS) and objective response rate (ORR) as
measured by RECIST v1.1 in DKK1-high
and all patients.
Part A and Part B of the DisTinGuish study are currently being
conducted in the United States and
the Republic of Korea. Part A enrolled 25 first-line HER2- G/GEJ
cancer patients. As of December 10,
2021, the median PFS for all patients in Part A was 10.7
months, with 11.9 months PFS for DKK1-high patients, and the ORR for all patients
who had completed a full cycle of therapy was 68%, with 90% ORR for
DKK1-high patients. Part B of the
study has enrolled 51 patients with second-line DKK1-high G/GEJ cancer. Additional follow-up data
from Part A is expected to be presented in the third quarter 2022
and from Part B in the fourth quarter 2022.
Colorectal Cancer
The DeFianCe study is a Phase 2 study of DKN-01 in combination
with bevacizumab and SOC chemotherapy in patients with advanced
colorectal cancer who have received one prior systemic therapy. The
study is designed with an initial 20 patient cohort and to then
expand into a 130 patient randomized controlled trial against
bevacizumab and SOC chemotherapy. The primary objective is PFS.
Secondary objectives include ORR, duration of response (DOR), and
OS. The study is expected to enroll its first patient in the third
quarter 2022.
Endometrial Cancer
The investigator-initiated trial of DKN-01 in combination with
pembrolizumab is an open-label, Bayesian design, Phase 2 trial and
will initially enroll 15 patients each into DKK1-high and DKK1-low cohorts. If the efficacy criteria is met
in either or both of the 15 patient cohort(s), then the cohort(s)
will be expanded by an additional 15 patients. The primary
objective of the study is ORR. Secondary objectives include
clinical benefit rate (CBR), PFS, OS, and DOR. The study is
expected to enroll its first patient in the fourth quarter
2022.
Leap has previously studied DKN-01 as a monotherapy and in
combination with paclitaxel in patients with endometrial cancer. In
the group of 23 patients treated with DKN-01 monotherapy for
whom DKK1 expression data was available, patients
with DKK1-high tumors achieved 1 complete response and 1
partial response, along with greater ORR (25% vs. 0%), CBR (63% vs.
7%), and median PFS (4.3 months vs. 1.8 months [HR 0.26; 95 CI:
0.09, 0.75]) compared to patients with DKK1-low tumors. In the
group of 24 patients treated with DKN-01 plus paclitaxel, 72% of
whom had received three or more prior systemic
therapies, DKK1-high patients 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.
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 and has an
important role in promoting tumor proliferation, metastasis,
angiogenesis, and in mediating an immune 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 the Leap/BeiGene
Collaboration
Leap is conducting the DisTinGuish study as part of an exclusive
option and license agreement with BeiGene for the development of
DKN-01 in Asia (excluding
Japan), Australia, and New
Zealand. Leap retains exclusive rights for the development,
manufacturing, and commercialization of DKN-01 for the rest of the
world.
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 being developed in patients with
esophagogastric, gynecologic, colorectal, and prostate cancers.
Leap has entered into a strategic collaboration 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/.
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 forward-looking
statements include statements regarding Leap's business strategies,
collaborations and partnerships, and expectations with respect to
the development and advancement of DKN-01 in clinical trials,
including the outcomes, status and timing of current or future
studies. 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: the uncertain
clinical development process, including the risk that clinical
trials may not have an effective design or generate positive
results; 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; unstable global market and economic conditions; the
accuracy of our estimates regarding expenses, future revenues,
capital requirements and needs for financing; the benefits to be
derived from our agreement with BeiGene, Ltd. ("BeiGene") or any
other collaborations, license agreements, or other acquisition
efforts; the rate and degree of market acceptance of DKN-01; the
success of other competing therapies that may become available; the
manufacturing capacity for DKN-01; our ability to maintain and
protect our intellectual property rights; and other risks and
uncertainties. Detailed information regarding factors that may
cause actual results to differ materially from expectations is
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, 2021, as filed
with the SEC on March 11, 2022 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
Matthew DeYoung
Investor Relations
Argot Partners
212-600-1902
leap@argotpartners.com
View original content to download
multimedia:https://www.prnewswire.com/news-releases/leap-therapeutics-announces-initiation-of-new-dkn-01-clinical-trials-in-gastric-cancer-colorectal-cancer-and-endometrial-cancer-301584158.html
SOURCE Leap Therapeutics, Inc.