Leap Therapeutics Announces Exciting Outcomes from DeFianCe Study
Sirexatamab has shown remarkable advancements in progression-free and overall survival in patients with elevated DKK1 levels.
Increased levels of DKK1 correlate with further benefits, improving patient outcomes for those treated with sirexatamab.
Leap Therapeutics remains dedicated to advancing sirexatamab for patients suffering from high DKK1 expressing colorectal cancer.
Leap Therapeutics, Inc. (NASDAQ: LPTX), a biotechnology firm specializing in targeted therapies and immuno-oncology, has unveiled the final data from Part B of the DeFianCe study. This Phase 2 trial assessed sirexatamab (DKN-01), an innovative monoclonal antibody, in combination with chemotherapy and bevacizumab, compared to standard combinations of the latter agents in patients with microsatellite stable (MSS) colorectal cancer who had prior systemic treatment. This pivotal data was presented by Dr. Zev Wainberg, a noted physician and Co-Director of the GI Oncology Program at UCLA, during a session at the European Society for Medical Oncology (ESMO) Congress 2025.
Dr. Wainberg explained, "Circulating DKK1 serves as a negative prognostic marker, particularly in patients experiencing advanced stages of metastatic colorectal cancer. The findings at ESMO highlight that sirexatamab, through its innovative mechanism of action, significantly enhances survival prospects for patients with elevated DKK1, who traditionally face poor prognoses with current standard care."
The DeFianCe study was conducted in two parts, with Part A involving 33 patients who demonstrated early progression on their first-line treatments or had progression with existing therapies including bevacizumab, among other characteristics. Following the initial phase, Part B was executed as a randomized controlled trial enrolling 188 participants. The primary endpoint was to assess progression-free survival (PFS), coupled with secondary measures of objective response rate (ORR), duration of response, and overall survival (OS). A notable exploratory group within the study comprised patients exhibiting high levels of circulating DKK1, evaluated through a specified biomarker assay.
Highlighted Outcomes from Part B of the DeFianCe Study:
- In patients with elevated DKK1 (upper median, n=88):
- Objective response rate was recorded at 38.0% for the Sirexatamab Arm, in contrast to 23.7% for those on the Control Arm.
- Median progression-free survival (mPFS) was 9.03 months in the Sirexatamab group vs. 7.06 months in the Control Arm, with a Hazard Ratio (HR) of 0.61 and a p-value of 0.0255.
- Median overall survival (mOS) was not reached in the Sirexatamab group versus 14.39 months for the Control group, HR of 0.42 and a p-value of 0.0118.
- For patients with the highest DKK1 levels (upper quartile, n=44):
- Objective response rate was noted at 44.0% in the Sirexatamab Arm as opposed to 15.8% in the Control Arm.
- Median progression-free survival was 9.36 months for the Sirexatamab Arm compared to 5.88 months for the Control Arm, with a HR of 0.46 and p-value of 0.0168.
- Median overall survival was not reached in the Sirexatamab group, versus 9.66 months in the Control group, HR 0.17 and p-value < 0.001.
- In the overall intent-to-treat population (n=188):
- The overall objective response rate stood at 35.1% in the Sirexatamab Arm compared to 26.6% in the Control.
- Median progression-free survival reflected at 9.2 months for Sirexatamab compared to 8.3 months for Control, HR of 0.84, and p-value at 0.1712.
- Event-free rate began favoring the Sirexatamab Arm from month 9 (53 vs. 47%) and further progressed to month 12 (34 vs. 23%).
- Sirexatamab, when paired with chemotherapy and bevacizumab, demonstrated safety and tolerability:
- The overall treatment-emergent adverse effects (TEAE) profile remained similar between the Sirexatamab and Control Arms, suggesting no difference in the safety profile with the combination therapy.
Douglas E. Onsi, President and CEO of Leap Therapeutics, commented on the significance of these results, stating, "The data from the DeFianCe study highlights the substantial promise of sirexatamab in the treatment of advanced colorectal cancer. Patients confronting this challenging disease, particularly those exhibiting heightened DKK1, frequently experience poor survival rates and limited therapeutic options. Sirexatamab has established itself as a potential groundbreaking agent, providing deep and lasting benefits for these patients. Following a recent funding round, we intend to consult with regulatory bodies regarding the path forward for sirexatamab and refine the DKK1 biomarker diagnostic test, ensuring it accurately identifies patients at risk."
About Leap Therapeutics
Leap Therapeutics (NASDAQ: LPTX) is dedicated to the advancement of targeted and immuno-oncology therapies. Their pipeline features sirexatamab (DKN-01), which targets the Dickkopf-1 (DKK1) protein, alongside FL-501, a humanized monoclonal antibody directing growth and differentiation factor 15 (GDF-15). Leap has initiated a strategy focusing on digital assets following a considerable private placement, aiming to foster long-term shareholder value while propelling the development of both sirexatamab and FL-501. For more information about Leap Therapeutics, visit http://www.leaptx.com or consult their SEC public filings available via EDGAR.
Frequently Asked Questions
What is the main focus of Leap Therapeutics?
Leap Therapeutics focuses on developing targeted and immuno-oncology therapeutics to improve cancer treatment outcomes.
What is the DeFianCe study about?
The DeFianCe study explored the safety and efficacy of sirexatamab in patients with colorectal cancer, particularly targeting those with high DKK1 expression.
What were the key findings of the DeFianCe study?
The study reported significant improvements in progression-free survival and overall survival for patients treated with sirexatamab compared to standard treatments.
What does high DKK1 indicate?
High levels of DKK1 in patients are associated with poorer outcomes in colorectal cancer, making it a key focus for targeted therapies like sirexatamab.
What are the future plans for sirexatamab?
Leap Therapeutics plans to work with regulatory authorities to advance sirexatamab through the clinical development pipeline, focusing on registering it for use in colorectal cancer treatment.
