Leap Therapeutics Reports Updated Results from DeFianCe Study, Initiates Strategic Review to Preserve Shareholder Value

Strategic Insights -

Leap Therapeutics, a biotechnology company focused on developing targeted and immuno-oncology therapeutics, reported updated results from the DeFianCe study, a Phase 2 study of sirexatamab (DKN-01), an anti-DKK1 monoclonal antibody, in combination with bevacizumab and chemotherapy, in patients with advanced microsatellite stable (MSS) colorectal cancer (CRC) who have received one prior systemic therapy for advanced disease. The company also announced that it has initiated a process to explore strategic alternatives to preserve and maximize shareholder value.

The updated results from the DeFianCe study demonstrated a statistically significant benefit in patients with high levels of DKK1, no prior exposure to anti-VEGF therapy, or liver metastasis, with a positive trend on overall response rate (ORR) and progression-free survival (PFS) in the full second-line CRC population.

Key Takeaways:

  • Sirexatamab demonstrated a statistically significant benefit in patients with high levels of DKK1, no prior exposure to anti-VEGF therapy, or liver metastasis, with a positive trend on ORR and PFS in the full second-line CRC population.
  • The DeFianCe study update showed a positive trend on ORR, by investigator assessment (IA) and blinded independent central review (BICR), and PFS in the full second-line CRC population, driven by the statistically significant benefit in patients with high levels of DKK1, no prior exposure to anti-VEGF therapy, or liver metastasis.
  • The company has initiated a process to explore strategic alternatives to preserve and maximize shareholder value, including leveraging its cash balance and exploring potential sale or partnership opportunities for sirexatamab and FL-501.
  • Leap reported that it will implement a workforce reduction of approximately 75% over the next two months as the DeFianCe study completes, with total cash payments and costs related to this reduction in force estimated to be approximately $3.2 million.
  • The company's Board of Directors has approved the engagement of Raymond James & Associates, Inc. to serve as exclusive financial advisor to assist in the strategic evaluation process.

Statistics:

  • 9.2 months median PFS in the sirexatamab arm, compared to 8.31 months in the control arm (HR 0.84, 95% CI: 0.57, 1.22, p = 0.1749)
  • 35.1% ORR by IA in the sirexatamab arm, compared to 26.6% in the control arm (p = 0.1009)
  • 33.0% ORR by BICR in the sirexatamab arm, compared to 20.2% in the control arm (p = 0.0203)
  • 21 patients remaining on study drug in the sirexatamab arm, compared to 15 patients in the control arm

Sources:

  • Leap Therapeutics, Inc. (2025). "Leap Therapeutics Reports Updated Results from DeFianCe Study, Initiates Strategic Review to Preserve Shareholder Value." PR Newswire.
  • Leap Therapeutics, Inc. (2025). "Part B of the DeFianCe study: Updated results." Leap Therapeutics website.