Multicenter phase 2 trial of second-line DKN-01 plus tislelizumab for advanced GEA with high DKK1 expression

DKN-01 is an antibody targeting Dickkopf-related protein 1 (DKK1). Part B of the multinational phase 2 DisTinGuish study evaluated the combination of DKN-01 and tislelizumab (anti-PD1) as second-line therapy for advanced gastroesophageal adenocarcinoma with high DKK1 expression. In the safety population, 40.4% of patients reported at least 1 DKN-01-related adverse events, most of which were low-grade. The objective response rate was 21.7% in the overall population and 31.8% in the PD-L1 ≥ 5% population, with disease control rate 34.8% in the overall population. The median PFS was 1.4 months and the median OS was 8.2 months. The authors conclude that the combination of DKN-01 and tislelizumab was safe and tolerable and showed activity as second-line therapy for advanced gastroesophageal adenocarcinoma with high DKK-1 expression.