Combination Therapy for Gastroesophageal Cancer

(AACR-ADOPT-GEA Trial)

This trial seeks the best combination of treatments for individuals with stomach or esophageal cancer. Participants will first undergo testing to identify specific markers in their tumors, which will guide the selection of the most effective combination of chemotherapy, immunotherapy, and targeted drugs. The goal is to determine if some patients can avoid surgery if their cancer responds well to these treatments. Ideal candidates for this trial have stomach or esophageal adenocarcinoma deemed removable by surgery, are willing to undergo tumor testing, and can tolerate the treatment plan and follow-up visits. As a Phase 2 trial, this research measures how well the treatment works in an initial, smaller group of people.

Previous studies have shown that zolbetuximab is generally well-tolerated when combined with chemotherapy for treating stomach and gastroesophageal junction cancers. Most patients did not experience severe side effects, though some reported more serious effects like nausea and vomiting, which were uncommon.

For the combination of zanidatamab and tislelizumab, less clear safety data is available. Zanidatamab targets HER2-positive cancer cells, and similar drugs have been used safely for other conditions. Tislelizumab aids the immune system in fighting cancer and can cause immune-related side effects, which are usually manageable.

Researchers are excited about these treatments for gastroesophageal cancer because they combine innovative biologics with traditional chemotherapy to offer a potentially more effective approach. Zolbetuximab and zanidatamab are monoclonal antibodies that target specific proteins on cancer cells, CLDN18.2 and HER2 respectively, which are not the focus of traditional chemotherapy like fluorouracil or oxaliplatin. Tislelizumab, an anti-PD-1 antibody, is included to enhance the immune system's ability to attack cancer cells, offering a novel mechanism of action compared to standard treatments. This combination could provide better targeting of cancer cells and improved overall response rates, making it an exciting development in the treatment landscape.

This trial will evaluate two separate combination therapies for gastroesophageal cancer. One treatment arm will study the combination of Zolbetuximab and Tislelizumab. Research shows that Zolbetuximab targets a protein called CLDN18.2, often found in these cancers, and helps the immune system attack cancer cells. Tislelizumab is a drug that enhances the immune system's ability to recognize and destroy cancer cells. Studies have shown that Tislelizumab, when combined with chemotherapy, improves outcomes for patients with these cancers.