In the study, high levels of tumoral DKK1 expression correlated with improved clinical outcomes in heterogeneous EGC patients treated with DKN-01 as monotherapy or in combination with pembrolizumab or paclitaxel. Pooled data for the 69 patients in the study for whom tumoral DKK1 expression data is available demonstrated that DKK1-high patients experienced higher overall response rates (ORR), a doubling of median progression-free survival (PFS), and longer median overall survival (OS) as compared to DKK1-low patients.

69 EGC pts were enrolled to receive D alone or in combination with pac or pem and had tumoral DKK1 expression available. 59 pts had adenocarcinoma [19 esophageal (28%), 40 GEJ/gastric (58%)]...23 pts with DKK1 high (H-score ≥ upper-tertile [≥39]) had an ORR of 22% (5 PR/23), DCR of 57% (13/23) while DKK1 low (H-score <39) had an ORR of 2% (1/46) and DCR of 26% (12/46). Median PFS was 12.1 weeks in DKK1 high vs. 6.0 weeks in DKK1 low; HR of 0.58 (95%CI: 0.34, 1.0). Median OS was 31.6 weeks in DKK1 high vs. 18 weeks in DKK1 low; HR of 0.70 (95%CI: 0.38, 1.3). Subgroup of pts (n=9) with immune checkpoint inhibitor (ICI) refractory disease treated with D + pem demonstrated longer PFS and OS for DKK1 high pts (H-score ≥39, n=4) vs DKK1 low (n=5): PFS 12.8 weeks vs 6.0 weeks; HR of 0.16 (95%CI: 0.02, 1.5) and OS 46 weeks vs. 16 weeks, respectively; HR of 0.22 (95%CI: 0.03, 2.0). High levels of tumoral DKK1 expression correlate with improved clinical outcomes in heterogeneous EGC pts treated with D monotherapy or in combination.