#United States #Cambridge #Leap Therapeutics #Sirexatamab #DeFianCe Study

Leap Therapeutics Presents Groundbreaking Findings at ESMO 2025

Leap Therapeutics, Inc. (Nasdaq:LPTX), a biotechnology company specializing in targeted and immuno-oncology therapeutics, has unveiled the final data from the pivotal Phase 2 DeFianCe study (NCT05480306) during the ESMO Congress 2025 held in Berlin, Germany. The study highlights the remarkable efficacy of sirexatamab (DKN-01), an innovative monoclonal antibody targeting the DKK1 protein, especially in colorectal cancer patients who demonstrate high DKK1 levels.

Overview of the DeFianCe Study

The DeFianCe study consisted of two parts. The second part (Part B) was a randomized controlled trial, which included a thorough evaluation of patients diagnosed with microsatellite stable (MSS) colorectal cancer (CRC) who had previously undergone systemic treatment for advanced disease. The study primarily focused on progression-free survival (PFS) and overall survival (OS) as its key objectives.

Dr. Zev Wainberg, who presented the study's results, cited that the circulating DKK1 levels serve as a negative prognostic indicator in patients suffering from advanced metastatic CRC. Notably, patients exhibiting elevated DKK1 levels are less likely to respond favorably to conventional therapies. The study's outcome demonstrably showed that sirexatamab could potentially offer critical survival advantages in these specific patient populations.

Key Findings from Part B of the DeFianCe Study

The data revealed significant improvements across multiple parameters:

• - In the subset of patients with DKK1-high levels (n=88), the overall response rate (ORR) was recorded at 38.0% for those in the Sirexatamab Arm, contrasting with 23.7% in the Control Arm.
• - The median PFS was also promising, reporting 9.03 months for the Sirexatamab Arm versus 7.06 months for the Control Arm, with a hazard ratio (HR) of 0.61 (p-value = 0.0255).
• - Overall survival figures were particularly noteworthy: the Sirexatamab Arm achieved an unquantified median OS compared to 14.39 months in the Control Arm (HR 0.42, p-value = 0.0118).

The heightened response and improved survival rates persisted, even when analyzing patients with DKK1-high (upper quartile) levels (n=44), which scored an ORR of 44.0% relative to only 15.8% in the Control Arm. The median PFS reached 9.36 months, further solidifying the benefits of incorporating sirexatamab into CRC treatment strategies.

Safety and Tolerability

Importantly, combining sirexatamab with chemotherapy and bevacizumab yielded a safety profile analogous to that of the Control Arm. The overall treatment-emergent adverse effects (TEAE) were comparable, indicating that sirexatamab does not compromise patient safety when used with standard care protocols.

Future Directions for Leap Therapeutics

Leap’s leadership, including President and CEO Douglas E. Onsi, articulated the company’s intention to build upon these encouraging results. With plans to engage regulatory authorities concerning the clinical path for sirexatamab in CRC, Leap is determined to optimize the distinct DKK1 biomarker diagnostic test, which could further aid in identifying patients most likely to benefit from this targeted therapy.

As Leap Therapeutics continues to pave the way in cancer treatment with its innovative approaches, the findings from the DeFianCe study stand as a pivotal moment in advancing therapeutic options for colorectal cancer patients, especially those facing dire prognoses due to high DKK1 expression levels.

Conclusion

The positive clinical results from the DeFianCe study present a significant step forward in addressing the unmet needs for advanced colorectal cancer patients. With sirexatamab’s unique targeting of DKK1 and its demonstrated potential for enhancing survival outcomes, Leap Therapeutics is poised to make a meaningful impact in the oncology landscape.