Multicenter phase 2a trial of first-line DKN-01 plus tislelizumab and chemotherapy for advanced gastroesophageal adenocarcinoma

The multicenter phase 2a DisTinGuish trial in the United States evaluated the DKK1-neutralizing antibody DKN-01 in combination with fluoropyrimidine/oxaliplatin chemotherapy and tislelizumab (anti-PD-1) as first-line therapy for advanced gastroesophageal adenocarcinoma (aGEA). All patients had at least one treatment-emergent adverse event, of which 96% were attributed to the CAPOX chemotherapy. Grade 3 or higher adverse events attributend to DKN-01 were reported for 24% of patients. The objective response rate was 73% (95% CI 49.8-89.3) and the disease control rate was 95%; the ORR was 90% (55.5-99.7) in the DKK1-high tumor patients. Median progression-free survival and overall survival were 11.3 months (95% CI 5.8-12.0) and 19.5 months (15.2-24.4), respectively, with 12-month PFS rate 33% and 18-month OS rate 55%. The authors conclude that DKN-01 could be safely combined with frontline CAPOX and tislelizumab and demonstrated encouraging activity.