A phase 3 trial shows that zolbetuximab improved survival in patients with advanced gastric or gastroesophageal junction cancer.
The targeted treatment, zolbetuximab, combined with chemotherapy extended survival in patients with advanced gastric or gastroesophageal junction cancer that is HER2 negative and overexpressing of CLDN 18.2, according to the phase 3 international GLOW and SPOTLIGHT trials. Both of these stomach cancers showed a specific biomarker.
This studies’ results prompted a grant for priority review from the Food and Drug Administration. The decision on whether or not to approve the therapy is set to finalize on Jan. 12, 2024.
This study is significant for patients with specific stomach cancers, as, if approved, this will be the first targeted therapy is to treat patients with advanced gastric or gastroesophageal junction cancers.
“Currently, standard chemotherapy regimens are the only treatment options for many patients with HER2-negative and low PD-L1 gastric and gastroesophageal cancer, and survival is about 12 months. A new treatment for these patients would address a significant unmet need to extend survival,” Dr. Manish Shah, the Bartlett Family Professor of Gastrointestinal Oncology and director of the Gastrointestinal Oncology Program in the Division of Hematology and Medical Oncology at Weill Cornell Medicine, explained in a press release.
Gastric cancer is one of the leading cancers in the world, and most patients with gastric cancer begin with mild or unseen symptoms, so once a diagnosis typically occurs, it may be in the later stages. Treatments for gastric cancer include immunotherapy (typically for patients with PD-L1—positive tumors) and Herceptin ([trastuzumab] patients with HER2-positive tumors). However, some patients fit neither of these categories; these tumors tend to have high levels of CLDN 18.2.
Zolbetuximab is a monoclonal antibody that binds to CLND18.2, which kills cancer cells after alerting the immune system to respond, according to Weill Cornell Medicine.
The trial evaluated 507 untreated patients with HER2-negative locally advanced or metastatic gastric or gastroesophageal junction cancer. These patients were randomized to receive zolbetuximab in combination with capecitabine plus oxaliplatin chemotherapy (CAPOX) or a placebo plus CAPOX, according to the press release.
Results showed that the zolbetuximab treatment improved progression-free survival (time from treatment until death or disease worsening) in comparison with the placebo treatment. The zolbetuximab treatment also decreased the risk of disease progression or death (31%). The zolbetuximab treatment showed an average 8.21-month progression-free survival compared to the placebo treatment, which was 6.8 months.
Overall survival (time from treatment until death of any cause) increased with the zolbetuximab treatment, and the risk of death decreased by 23%. The average overall survival median increased a little over two months with zolbetuximab.
Side effects were similar between both groups, but this was expected, according to Shah. The use of zolbetuximab didn’t add any extra symptoms.
Shah also participated in a 2023 study that focused on treatment with zolbetuximab as well, working with Astellas Pharma, the creators of zolbetuximab.
“We now have evidence from two large trials showing that the addition of zolbetuximab provides a meaningful survival benefit for patients with CLDN 18.2-positive gastric cancers. If zolbetuximab is approved, patients will be able to decide with their physicians whether zolbetuximab plus CAPOX or mFOLFOX is the right regimen for them,” explained Shah in a press release.
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