(HealthDay News) — For patients with human epidermal growth factor receptor 2 (HER2)-negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma, zolbetuximab, a monoclonal antibody that targets claudin-18 isoform 2 (CLDN18.2), plus capecitabine and oxaliplatin (CAPOX) prolongs progression-free survival (PFS) and overall survival (OS) versus placebo plus CAPOX, according to a study published online July 31 in Nature Medicine.
Manish A. Shah, M.D., from Weill Cornell Medical College in New York City, and colleagues conducted a phase 3 study to examine zolbetuximab plus CAPOX as first-line treatment for CLDN18.2-positive, HER2-negative, locally advanced unresectable or mG/GEJ adenocarcinoma in 507 patients randomly assigned to zolbetuximab plus CAPOX or placebo plus CAPOX in a 1:1 ratio.
The researchers found that PFS, the primary end point, was significantly prolonged for patients randomly assigned to receive zolbetuximab versus placebo (median, 8.21 versus 6.90 months; hazard ratio [HR], 0.687), as was OS, the key secondary end point (median, 14.39 versus 12.16 months; HR, 0.771). Treatment-emergent adverse events of grade 3 or higher occurred in 72.8 and 69.9 percent of those receiving zolbetuximab and placebo, respectively.
“We now have evidence from two large trials showing that the addition of zolbetuximab provides a meaningful survival benefit for patients with CLDN18.2-positive gastric cancers,” Shah said in a statement. “If zolbetuximab is approved, patients will be able to decide with their physicians whether zolbetuximab plus CAPOX or mFOLFOX [folinic acid plus 5-fluorouracil and oxaliplatin] is the right regimen for them.”
Several authors disclosed ties to the biopharmaceutical industry, including Astellas Pharma Inc., which funded the study and manufactures zolbetuximab.