Leap Therapeutics, Inc. announced the Company will be presenting updated data from Part B of the DisTinGuish study evaluating DKN-01 in combination with tislelizumab, BeiGene's anti-PD-1 antibody, in second-line gastroesophageal adenocarcinoma (GEA) cancer patients whose tumors express high levels of DKK1 (DKK1-high) at the Society of Immunotherapy for Cancer (SITC) 37th Annual Meeting being held in Boston, MA on November 8-12, 2022. Leap is also presenting preclinical DKN-01 data supporting the DeFianCe study, a Phase 2 study of DKN-01 in combination with bevacizumab and standard of care chemotherapy in patients with advanced colorectal cancer (CRC) who have received one prior systemic therapy. Key Findings DisTinGuish; DKN-01 and tislelizumab administered in DKK1-high (H-score > 35), PD-1 naïve patients were well tolerated at both 300mg and 600mg DKN-01 doses.

Higher DKN-01 dose at 600mg was not associated with higher frequency of adverse events (AEs). There were no Grade 5 treatment-emergent AEs (TEAE) and no TEAEs leading to study drug discontinuation or dose reduction. High and durable 27% overall response rate (ORR) in evaluable anti-PD-1/PD-L1 naïve mITT population (n=43).

55% ORR, 73% disease control rate, and 7.7 months median progression-free survival in DKK1-high/PD-L1-high vCPS = 10 patients (n=12: 6 PR, 2 SD, 3 PD, 1 NE). 27% ORR in DKK1-high/PD-L1-negative vCPS < 1 patients (n=11: 3 PR, 1 SD, 7 PD). Overall, 7 of 10 responders remain on therapy.

Key Findings Preclinical CRC; DKN-01 showed additive activity with 5-fluorouracil (5-FU) and can overcome 5-FU-resistance in two CRC xenograft models, resulting in tumor regressions. 5-FU-resistant models are reflective of a second-line CRC population currently being recruited in the DeFianCe study (NCT05480306). DKN-01 as monotherapy or in combination with anti-PD-1 resulted in tumor regression in a CT26 syngeneic CRC model.

Treatment increased PD-L1 immunoreactivity. Promoted substantial tumor necrosis which was associated with a robust immune cell infiltrate. Tumor immune infiltrate contained a substantial number of CD3+ and CD8+ cells, implying the presence of an adaptive immune response to tumor antigen.