DKN-01 Plus Tislelizumab and Chemotherapy Shows Promise in Advanced Gastric Cancer
核心洞察
A phase IIa trial of DKN-01 with tislelizumab and chemotherapy demonstrated a 73% objective response rate in advanced gastric or gastroesophageal junction adenocarcinoma (搜索).
Median progression-free survival was 11.3 months, and median overall survival reached 19.5 months in patients treated with the DKN-01 combination therapy.
The combination showed activity regardless of PD-L1 expression, suggesting a potential benefit for a broad range of patients with advanced gastric cancer.
A phase IIa study, named DisTinGuish, published in the Journal of Clinical Oncology, reveals that the DKK1 (搜索)-neutralizing antibody DKN-01, combined with tislelizumab and chemotherapy, exhibits notable activity in the first-line treatment of advanced gastric or gastroesophageal junction adenocarcinoma (搜索).
The multicenter trial involved 25 patients who received intravenous DKN-01 (300 mg every 2 weeks), tislelizumab (200 mg every 3 weeks), oxaliplatin (130 mg/m2 every 3 weeks), and capecitabine (1,000 mg/m2 twice daily on days 1 to 15 of each 21-day cycle).
Efficacy Outcomes
Among the 22 patients evaluable for response, the objective response rate (ORR) was 73% (95% CI = 49.8%-89.3%), with a disease control rate of 95%. In patients with varying DKK1 (搜索) tumor status, the ORRs were 90% (95% CI = 55.5%-99.7%) in DKK1-high tumors (n=12) and 67% (95% CI = 29.9%-92.5%) in DKK1-low tumors (n=9). For PD-L1 expression, the ORRs were 86% (95% CI = 57.2%-98.2%) in patients with a combined positive score (CPS) < 5 (n=16) and 67% (95% CI = 22.3%-95.7%) in those with a CPS ≥ 5 (n=6).
The median progression-free survival (PFS) was 11.3 months (95% CI = 5.8-12.0 months), with a 12-month PFS rate of 33%. The median overall survival (OS) was 19.5 months (95% CI = 15.2-24.4 months), with 12- and 18-month OS rates of 76% and 55%, respectively.
Safety Profile
Grade ≥ 3 adverse events were reported in 60% of patients. The most common were diarrhea (20%), decreased potassium (16%), and decreased hemoglobin (12%). A single treatment-related death occurred due to pulmonary embolism. Adverse events of any grade related to DKN-01 included fatigue (28%), diarrhea (28%), decreased neutrophils (28%), and nausea (24%).
Investigator Commentary
The investigators concluded that “DKN-01 can be safely combined with frontline fluoropyrimidine/oxaliplatin and tislelizumab and demonstrates encouraging activity independent of PD-L1 expression levels. A randomized phase II trial is ongoing (ClinicalTrials.gov identifier NCT04363801).”