On January 16, 2024 Leap Therapeutics, Inc. (Nasdaq:LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, reported new data from Part A of the DeFianCe study, a Phase 2 study evaluating DKN-01, Leap’s anti-Dickkopf-1 (DKK1) antibody, in combination with standard of care bevacizumab and chemotherapy in second-line patients with advanced colorectal cancer (CRC), to be presented at the upcoming 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium taking place in San Francisco, CA and virtually on January 18-20, 2024 (Press release, Leap Therapeutics, JAN 16, 2024, View Source [SID1234639261]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Data from Part A of the DeFianCe study demonstrates that the addition of DKN-01 to bevacizumab and chemotherapy can generate clinically meaningful response rates and durable tumor reductions with a favorable safety profile in second-line CRC patients, particularly those with rectal or rectosigmoid tumors," said Meredith Pelster, MD, Assistant Director of Gastrointestinal Research at Sarah Cannon Research Institute and a study investigator. "We are very interested in utilizing DKN-01 to modulate the Wnt pathway, which is active in a high percentage of CRC patients, particularly left-sided tumors, to overcome resistance to chemotherapy, and to decrease angiogenesis in order to enhance the activity of the standard of care bevacizumab plus chemotherapy regimens. These results provide a strong foundation for the randomized controlled Part B of this study, which is enrolling extremely well and expected to complete enrollment mid-year."

"In this heterogenous second-line population with several unfavorable characteristics, the DKN-01 plus bevacizumab and chemotherapy Part A ORR of 30%, with a disease control rate of over 90%, and enhanced activity in left-sided tumors and rectal tumors, with a 46% ORR and 9.4 month preliminary PFS, represent an encouraging efficacy signal," said Zev Wainberg, MD, Professor of Medicine and Co-Director of the GI Oncology Program at UCLA. "CRC is a heterogenous disease where the selection of therapy and expected outcomes vary based on whether the tumor is on the left or right side, the presence or absence of genetic mutations, microsatellite instability, and prior therapy. Physicians want to be able to select a second-line therapy combination based on the patient’s personalized tumor characteristics, which is what we hope to achieve by adding DKN-01 and understanding the subgroups with the greatest clinical benefit."

Leap will host a conference call on January 23, 2024 at 8:30 a.m. Eastern Time in which Dr. Pelster and Dr. Wainberg will further discuss the new data from the DeFianCe study.

Key Findings:

· As of the December 6, 2023 data cutoff, 33 patients enrolled in Part A of the DeFianCe study
· Across all evaluable patients with second-line microsatellite stable CRC (n=27):
o Objective response rate (ORR) was 30% and disease control rate (DCR) was 93%, including 8 partial responses (PR) and 17 patients with a best response of stable disease (SD)
o Median progression-free survival (PFS) was 6.3 months
o 9 patients remain on therapy beyond 8.5 months
· Analysis revealed a breadth of clinical activity across additional subgroups, including patients with left-sided tumors (n=25)
o 33% ORR and 100% DCR in response-evaluable population (7 PRs, 14 SDs)
o Preliminary median PFS of 8.6 months (9 patients continuing on therapy within subgroup)
· Patients with rectal/rectosigmoid carcinomas (n=15) represent an important subpopulation:
o 46% ORR and 100% DCR in response-evaluable population (6 PRs, 7 SDs)
o Preliminary median PFS of 9.4 months (6 patients continuing on therapy within subgroup)
o Higher baseline plasma DKK1 levels correlated with improved responses
· DKN-01 plus bevacizumab and chemotherapy was well-tolerated, with a majority of DKN-01 related events being low grade (Grade 1/2)
· Randomized controlled Part B of the study is underway with 54 patients currently enrolled

Conference Call:

Leap’s management team, together with Dr. Pelster and Dr. Wainberg, will host a conference call on Tuesday, January 23, 2024 at 8:30 a.m. Eastern Time to further discuss the data. The conference call will be broadcast live in listen-only mode and can be accessed via the website URL: View Source A replay of the event will also be available for a limited time on the Investors page of the Company’s website at View Source

About the DeFianCe Study

The DeFianCe study (NCT05480306) is a Phase 2, open-label, global study of DKN-01 in combination with standard of care bevacizumab and chemotherapy in patients with advanced CRC who have received one prior systemic therapy for advanced disease. The Part A cohort enrolled 33 patients, including significant numbers of patients who had early progression on first-line therapy, previous exposure to bevacizumab, tumors with Ras mutations, or liver metastases. The study has expanded into a 130-patient Part B randomized controlled trial. The primary objective of the study is progression free survival. Secondary objectives include overall response rate, duration of response, and overall survival.