The novel agent, IMAB362, which stimulates the immune system to attack a certain protein expressed by many stomach cancer cells, has demonstrated a significant improvement in survival compared to standard therapy among patients with this disease. These results were presented at the 2016 annual meeting of the American Society of Clinical Oncology (ASCO).
Stomach cancer, often called gastric cancer, as well as cancers of the gastroesophageal junction (GEJ) (cancers arising from the location where the esophagus – tube that leads from the mouth to the stomach – and the stomach meet), occur in over 26,000 people in the United States every year.
Advanced gastric or GEJ cancers refer to cancer that has spread from its site origin to distant sites in the body. Standard therapy for these cancers results in suboptimal long-term survival rates, demonstrating a need for novel therapeutic approaches.
Researchers have identified a certain protein, called the Claudin 18.2 (CLDN18.2) protein that is expressed by several types of cancer cells, while not expressed by healthy cells. Therefore, the agent IMAB362 was developed to specifically target the CLDN18.2 protein. Once IMAB362 binds to the CLDN18.2 protein on cancer cells, the immune system is stimulated to attack the cancer cells.
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Researchers recently conducted a clinical trial, referred to as the FAST trial, to further evaluate the effectiveness of the addition of IMAB362 to chemotherapy in the treatment of patients with advanced gastric and GEJ cancers. The trial included 161 patients who had not received prior therapy, and whose cancer cells expressed CLDN18.2 proteins, as determined through laboratory processes.
One group of patients was treated with IMAB362 plus the chemotherapy combination consisting of epirubicin, oxaliplatin, and capecitabine (EOX), while the other group of patients was treated with EOX only.
- Median survival without progression of cancer was 7.9 months for those treated with IMAB362 plus EOX, and 5.7 months for those treated with EOX only.
- Median overall survival was 12.5 months for patients treated with IMAB362/EOX, compared with 8.7 months for those treated with EOX only.
- Among patients whose cancer had a very high expression of the CLDN18.2 protein, however, results were more pronounced. The median progression-free survival for patients with a very high expression of the CLDN18.2 protein was 9.1 months for those treated with IMAB362/EOX, compared with 6.1 months for those treated with EOX only.
- Median overall survival for patients with a very high expression of the CLDN18.2 protein was 16.6 months for those treated with IMAB362/EOX, compared to 9.3 months for those treated with EOX only.
- The addition of IMAB362 to EOX did not significantly increase severe side effects.
The researchers of the trial concluded that the addition of IMAB362 to standard chemotherapy significantly improves outcomes, including survival, among patients with advanced gastric or GEJ cancers that express the CLDN18.2 protein. Importantly, patients whose cancers express very high levels of CLDN18.2 proteins achieved an even greater benefit from therapy with IMAB362. Clinical trials further evaluating IMAB362 are ongoing to provide further data on the effectiveness of IMAB362 in these types of cancers.
Reference: Al-Batran S-E, Schuler M, Zvirbule Z, et al. FAST: An international, multicenter, randomized, phase II trial of epirubicin, oxaliplatin, and capecitabine (EOX) with or without IMAB362, a first-in-class anti-CLDN18.2 antibody, as first-line therapy in patients with advanced CLDN18.2+ gastric and gastroesophageal junction (GEJ) adenocarcinoma. Proceedings from the 2016 annual ASCO meeting. Abstract # LBA4001. Available at: FAST: An international, multicenter, randomized, phase II trial of epirubicin, oxaliplatin, and capecitabine (EOX) with or without IMAB362, a first-in-class anti-CLDN18.2 antibody, as first-line therapy in patients with advanced CLDN18.2+ gastric and gastroesophageal junction (GEJ) adenocarcinoma.. Accessed June 17, 2016.