CAMBRIDGE, Mass., Jan. 23, 2020 /PRNewswire/ -- Leap Therapeutics, Inc. (Nasdaq: LPTX) today presented updated clinical data from its recently completed Phase 1/2 clinical trial of DKN-01 in patients with advanced or recurrent esophagogastric cancer (EGC) at the 2020 ASCO GI annual meeting.
Updated response and survival data in the anti-PD-1/PD-L1 naïve gastric/gastroesophageal junction adenocarcinoma (GEA) subgroup of patients treated with DKN-01 plus KEYTRUDA® (pembrolizumab) was presented. As previously reported, there is a strong correlation between response and survival in patients whose tumors express high levels of DKK1, the target of DKN-01. These correlations continue to be seen with longer follow-up of these patients. Improvements in overall response rates, progression free and overall survival were observed independent of PD-L1 expression.
Leap and collaborators at Imaging Endpoints Research and Core Labs presented data on the potential correlation of radiometric measures of metastatic lesions with intratumoral DKK1 expression and other immune biomarkers in esophagogastric cancer patients treated with DKN-01 and pembrolizumab. Defined signatures from radiomic quantitative texture analysis may provide a useful biomarker to non-invasively evaluate DKK1 expression in future studies.
"The maturing data from this study continues to support that elevated DKK1 expression is a predictive biomarker for improved outcomes in patients treated by DKN-01 and anti PD-1/PD-L1 therapy," stated Samuel J. Klempner, MD, Assistant Professor, Massachusetts General Hospital Cancer Center and Harvard Medical School.
"The totality of data from our anti-PD-1 combination study is informing the design of the future study we recently announced in combination with BeiGene. We plan to evaluate DKN-01 with tislelizumab in second-line GEA patients whose tumors express high levels of DKK1 in addition to a novel first-line triplet combination in GEA patients to be treated with DKN-01, tislelizumab and chemotherapy," said Cynthia Sirard, M.D., Vice President, Clinical Development of Leap Therapeutics.
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, all of whom have had previous treatment with standard therapies. Many of these subjects have had multiple lines of prior therapy and/or rapidly growing tumors, 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 and has the secondary endpoints of ORR, PFS, and OS.
The combination of DKN-01 and pembrolizumab in GEA patients demonstrated improved outcomes in patients whose tumors are DKK1-high and who were PD-1/PD-L1 naïve. DKK1-high patients experienced over 22 weeks median PFS and nearly 32 weeks OS, with a 50% ORR and 80% DCR in ten evaluable patients. DKK1-low patients experienced nearly 6 weeks median 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. One-third of patients in the study were DKK1-high.
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. 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/.
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: 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, 2018, as filed with the SEC on April 1, 2019, and Leap's Quarterly Reports on Form 10-Q. 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.
Douglas E. Onsi
Chief Financial Officer
Leap Therapeutics, Inc.
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