China's National Medical Products Administration (NMPA) has approved Astellas Pharma Inc.'s zolbetuximab (VYLOY™) for the first-line treatment of patients with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are claudin (CLDN) 18.2 positive. This approval marks a significant advancement in the treatment landscape for gastric cancer in China, where the disease remains a major health challenge. Zolbetuximab is the first NMPA-approved monoclonal antibody to target gastric tumor cells expressing the CLDN18.2 biomarker.
The approval is based on data from the global Phase 3 GLOW and SPOTLIGHT clinical trials, which included patients from mainland China. These trials demonstrated that zolbetuximab, in combination with fluoropyrimidine- and platinum-containing chemotherapy, significantly improved progression-free survival (PFS) and overall survival (OS) compared to chemotherapy alone.
Clinical Trial Data
The GLOW trial evaluated zolbetuximab plus CAPOX (capecitabine and oxaliplatin) versus placebo plus CAPOX. Results showed a median PFS of 8.21 months in the zolbetuximab arm compared to 6.80 months in the placebo arm. The median OS was 14.39 months versus 12.16 months, respectively.
Similarly, the SPOTLIGHT trial assessed zolbetuximab plus mFOLFOX6 (oxaliplatin, leucovorin, and fluorouracil) versus placebo plus mFOLFOX6. The zolbetuximab arm achieved a median PFS of 10.61 months compared to 8.67 months in the placebo arm. The median OS was 18.23 months versus 15.54 months, respectively.
In both trials, the incidence of serious treatment-emergent adverse events (TEAEs) was comparable between the zolbetuximab and control groups. The most common TEAEs reported in the zolbetuximab arms were nausea, vomiting, and decreased appetite.
Expert Commentary
Professor Xu Ruihua, Lead Primary Investigator of the Phase 3 GLOW Study, stated, "Approximately 30% of patients enrolled in the global Phase 3 GLOW trial were from mainland China... We are excited that the NMPA has approved zolbetuximab, which will provide a valuable and effective first-line treatment option for patients with advanced gastric cancer in China."
Professor Xu Jianming, Lead Primary Investigator of the Phase 3 SPOTLIGHT Study in China, added, "We are extremely encouraged that the NMPA has approved zolbetuximab in China... The survival and safety benefits seen in the China subgroup were consistent with the global trial population, and the results are expected to have far-reaching implications for meeting the clinical needs of Chinese patients with advanced gastric cancer."
Impact and Prevalence
Gastric cancer is a significant health burden in China, being the third leading cause of cancer-related mortality. In 2022, there were over 260,000 deaths reported from the disease. Early detection is challenging, with approximately 60% of patients diagnosed at an advanced stage, leading to poor outcomes. The average five-year survival rate for advanced gastric cancer in China is 9.1%, underscoring the urgent need for novel therapeutic options.
Moitreyee Chatterjee-Kishore, Ph.D., M.B.A., Senior Vice President and Head of Immuno-Oncology Development at Astellas, noted that approximately 35% of Chinese patients with advanced gastric and GEJ cancers have tumors that positively express CLDN18.2. Zolbetuximab's targeted approach aims to stimulate selective cell death, reducing the overall number of CLDN18.2-positive cells in a tumor.
About Zolbetuximab
Zolbetuximab is a first-in-class monoclonal antibody specifically designed to target tumor cells that express CLDN18.2, a transmembrane protein. By binding to CLDN18.2, zolbetuximab induces cancer cell death and tumor growth inhibition through antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).
Astellas has already factored the impact of this NMPA approval into its financial forecast for the fiscal year ending March 31, 2025. The approval marks a significant step forward in providing a precision medicine approach for treating advanced gastric cancer in China.
