Astellas Pharma’s Zolbetuximab (Vyloy, Zolbetuximab) was approved by Japan, bringing new hope to gastric cancer patients

In March 2024, Astellas Pharmaceuticals received good news. The anti-CLDN18.2 monoclonal antibody drug Zolbetuximab (Vyloy, Zolbetuximab) it developed was officially approved by the Ministry of Health, Labor and Welfare (MHLW) of Japan on March 26. This innovative drug will be used to treat patients with CLDN18.2-positive, unresectable, advanced or recurrent gastric cancer, marking the birth of the world's first and currently only therapeutic drug targeting CLDN18.2.

Gastric cancer is a common malignant tumor. Its early symptoms are often similar to other gastric diseases, so it is often diagnosed in the late or metastatic stage. Despite the continuous efforts of the medical community, gastric cancer remains the third leading cause of cancer death in Japan, with 126,724 new cases in 2022. For refractory diseases such as advanced gastric adenocarcinoma, treatment options are extremely limited, and most are only discovered at an advanced stage. MHLW's approval of zotuximab undoubtedly brings new treatment hope to these patients, becoming the first and only targeted treatment option for patients with CLDN18.2-positive gastric cancer.

The approval of zotuximab was based on two pivotal Phase 3 clinical trials: SPOTLIGHT and GLOW. Both trials are targeting the first-line treatment of patients with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are CLDN18.2-positive. The trial results showed that compared with placebo plus chemotherapy, zotuximab combined with chemotherapy (mFOLFOX6 or CAPOX) showed significant advantages in both the primary endpoint of progression-free survival (PFS) and the key secondary endpoint of overall survival (OS).

In terms of safety, the most common adverse reactions of zotuximab combined with chemotherapy include nausea, vomiting, decreased appetite, neutropenia, and weight loss, but these reactions can be effectively controlled through measures such as antiemetics, dose interruption, and infusion rate adjustment.

It is worth noting that in the SPOTLIGHT and GLOW trials, approximately 38% of screened patients had tumors that were CLDN18.2 positive. To ensure accurate patient screening, Astellas has partnered with Roche Diagnostics to launch the newly approved VENTANA CLDN18 (43-14A) RxDx test. This is an immunohistochemistry (IHC) companion diagnostic test designed to identify patients who may be candidates for treatment with VYLOY. The test will be conducted at multiple central laboratories in Japan, with plans to gradually expand to more laboratories.

In addition, Astellas has submitted applications forVYLOY to multiple regulatory agencies around the world, and the review work is currently in progress. In the future, with the global promotion of zotuximab, more patients with CLDN18.2-positive gastric cancer are expected to benefit from this innovative therapy.