Leap Therapeutics, Inc. announced the company will be presenting data in first-line patients with advanced gastroesophageal adenocarcinoma (GEA) from the DisTinGuish study, a Phase 2a clinical trial evaluating Leap's anti-Dickkopf-1 (DKK1) antibody, DKN-01, in combination with tislelizumab, BeiGene's anti-PD-1 antibody, and chemotherapy, at the European Society for Medical Oncology (ESMO) Congress 2022 being held on September 9-12. Safety and early efficacy data will be presented from the WAKING study, a multicenter Phase 2 non-randomized trial evaluating DKN-01 plus Tecentriq® (atezolizumab), Roche's anti-PD-L1 antibody, in patients with advanced oesophagogastric adenocarcinoma (OGA). Key Findings DisTinGuish: DKN-01 and tislelizumab plus CAPOX was well tolerated in first-line treatment for advanced GEA patients, with a safety profile consistent with previous reports.

Overall median progression-free-survival (PFS) of 11.3 months exceeds benchmark results in unselected patients and in all four important biomarker-directed subgroups: 11.3 months PFS in DKK1-high and 12.0 months in DKK1-low, and 10.7 months PFS in PD-L1-low (CPS < 5) and 11.6 months in PD-L1-high (CPS > 5). Median overall survival (OS) is not mature with only 44% of patients deceased as of the data cut (June 30, 2022), with a median duration on study of 15.7 months and last patient enrolled in early April 2021. High and durable overall response rate (ORR) in unselected and aggressive subgroups (DKK1-high and PD-L1-low) (mITT): 68% (1 CR, 14 PR) overall: DKK1-high: 90% ORR (9 PR), DKK1-low: 56% ORR (1 CR; 4 PR), PD-L1-low expression: 79% (11 PR): 100% (6/6) ORR in DKK1-high, PD-L1-low patients.

PD-L1-high expression: 67% (1 CR; 3 PR): 75% (3/4) ORR in DKK1-high, PD-L1-high patients. Key Findings WAKING: DKN-01 up to 600mg every 2 weeks in combination with atezolizumab was considered safe: 3 patients with the longest time on treatment received the 600mg dose level. At time of data cut off (August 16, 2022), 18 patients were enrolled in the study: 12 patients were treated in initial phase, 10 patients were response evaluable at the time of data cut-off, 1 patient had a PR and DKK1 expression of 81% tumor percentage score (TPS), and Disease control rate: 50% (1 PR, 4 SD, 5 PD).

Elevated baseline DKK1 expression (TPS > 20%) may be associated with clinical response: 4 DKK1-high patients: Best ORR 25% (1 PR, 1 SD, 1 PD, 1 NE). Translational analyses and assessment of PD-L1 status are ongoing. Safety: No dose-limiting toxicity (DLT) was observed, and no formal maximum tolerated dose (MTD) was reached, and No treatment-related deaths occurred, and no dose reductions were required.