Leap Therapeutics reports results from Phase 2 study of sirexatamab

Leap Therapeutics (LPTX) announced final results from Part B of the DeFianCe study, a Phase 2 study of sirexatamab, an anti-DKK1 monoclonal antibody, in combination with bevacizumab and chemotherapy compared to bevacizumab and chemotherapy in patients with microsatellite stable, or MSS, colorectal cancer, or CRC, who have received one prior systemic therapy for advanced disease. The final clinical results were presented on behalf of the DeFianCe study investigators by Zev Wainberg, MD, Professor of Medicine and Co-Director of the GI Oncology Program at UCLA in a Mini Oral session at the European Society for Medical Oncology Congress 2025 in Berlin, Germany. The DeFianCe study was a two part, open-label, multi-country study. Part A of the DeFianCe study enrolled 33 patients, including a significant number of patients who had early progression on first-line therapy, previous exposure to bevacizumab, tumors with RAS mutations, or liver and lung metastases. The study expanded into a 188 patient Part B randomized controlled trial. The primary objective of the study was progression-free survival PFS. Secondary objectives included objective response rate, or ORR, duration of response, and overall survival, or OS. A key pre-defined exploratory population was those patients who had high levels of circulating DKK1, as measured by a biomarker assay. Key Part B DeFianCe Study Findings includes: Across the DKK1-high patients: ORR was 38.0% in the Sirexatamab Arm compared to 23.7% ORR in the Control Arm; mPFS was 9.03 months in the Sirexatamab Arm compared to 7.06 months in the Control Arm, Hazard Ratio 0.61, p-value = 0.0255; mOS was not reached in the Sirexatamab Arm compared to 14.39 months in the Control Arm, HR 0.42, p-value = 0.0118; Across the DKK1-high patients: ORR was 44.0% in the Sirexatamab Arm compared to 15.8% ORR in the Control Arm.