Astellas Pharma recently announced the approval Gastric Cancer of VYLOYTM (zolbetuximab) by China’s National Medical Products Administration (NMPA) for first-line treatment of locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma. This approval applies specifically to tumors that are claudin (CLDN) 18.2 positive. Zolbetuximab is notable for being the first NMPA-approved monoclonal antibody targeting CLDN18.2-positive gastric tumor cells, offering a precise and innovative approach to treating these challenging cancers.
The Burden of Gastric Cancer in China
Gastric Cancer represents a significant public health challenge in China. As the third leading cause of cancer-related mortality, it accounted for over 260,000 deaths in 2022 alone. Early detection is rare, with approximately 60% of cases diagnosed at advanced stages where therapeutic options are limited. The average five-year survival rate for advanced gastric cancer in China stands at just 9.1%, underscoring the urgent need for novel treatments that can improve survival and quality of life.
Groundbreaking Clinical Trial Results
The approval of zolbetuximab is underpinned by robust data from two Phase 3 clinical trials, GLOW and SPOTLIGHT. These studies evaluated the safety and efficacy of zolbetuximab combined with chemotherapy in patients with CLDN18.2-positive, HER2-negative gastric and GEJ cancers. Notably, a significant portion of the participants in these global trials were from mainland China, providing critical insights into the drug’s effectiveness within the Chinese population.
Key Findings from the GLOW Trial
The GLOW trial investigated zolbetuximab combined with CAPOX (a chemotherapy regimen of capecitabine and oxaliplatin) compared to a placebo plus CAPOX. Among eligible patients, Gastric Cancer treatment with zolbetuximab demonstrated statistically significant improvements in both progression-free survival (PFS) and overall survival (OS). Median PFS was 8.21 months for the zolbetuximab group versus 6.80 months for the placebo group. Similarly, median OS was 14.39 months with zolbetuximab compared to 12.16 months for the placebo group. These findings highlight the potential of zolbetuximab to extend survival in a patient population with limited options.
Key Findings from the SPOTLIGHT Trial
In the SPOTLIGHT trial, zolbetuximab was combined with mFOLFOX6 (a regimen of oxaliplatin, leucovorin, and fluorouracil) and compared to a placebo plus mFOLFOX6. Results again demonstrated significant survival benefits for zolbetuximab-treated patients. Median PFS was 10.61 months in the zolbetuximab group versus 8.67 months in the placebo group. Median OS was 18.23 months for zolbetuximab-treated patients compared to 15.54 months for those receiving placebo. These outcomes reinforce the efficacy of zolbetuximab as a first-line treatment option for advanced gastric cancer.
Perspectives from Clinical Experts
Prominent oncologists who participated in these trials have expressed optimism about the approval of zolbetuximab.
Professor Xu Ruihua, Director of the Cancer Prevention and Treatment Center of Sun Yat-sen University and President of the Chinese Society of Clinical Oncology (CSCO), emphasized the significant survival benefits observed in the GLOW trial. He noted, “The combination of zolbetuximab and chemotherapy has demonstrated meaningful improvements in survival and quality of life for patients with CLDN18.2-positive, HER2-negative advanced gastric and GEJ cancers. The approval of zolbetuximab represents a vital advancement in the treatment landscape for Chinese patients.”
Professor Xu Jianming, Lead Investigator of the SPOTLIGHT study in China and affiliated with the Fifth Medical Center of the Chinese People’s Liberation Army General Hospital, echoed these sentiments. “The results of the SPOTLIGHT trial provide compelling evidence for the efficacy and safety of zolbetuximab combined with chemotherapy as a first-line treatment. This approval marks a significant milestone in meeting the clinical needs of Chinese patients with advanced gastric cancer,” he stated.
Mechanism of Action: Precision Medicine in Practice
Zolbetuximab’s mechanism of action exemplifies the principles of precision medicine. Approximately 35% of Chinese patients with advanced gastric and GEJ cancers have tumors expressing the CLDN18.2 biomarker. By specifically targeting this biomarker, zolbetuximab induces selective cell death, reducing the tumor burden while sparing healthy tissues. This targeted approach not only improves treatment efficacy but also minimizes side effects, aligning with the broader goals of personalized oncology care.
Safety Profile and Tolerability
The GLOW and SPOTLIGHT trials also evaluated the safety profile of zolbetuximab. Serious treatment-emergent adverse events (TEAEs) occurred at similar rates in both the zolbetuximab and control groups. The most common all-grade TEAEs in the zolbetuximab group were nausea, vomiting, and decreased appetite. These findings suggest that zolbetuximab’s benefits in terms of survival are not compromised by an excessive safety burden, making it a viable option for widespread clinical use.
Strategic Implications for Astellas Pharma
The NMPA’s approval of zolbetuximab aligns with Astellas Pharma’s strategic commitment to advancing cancer care through innovative therapies.
Dr. Moitreyee Chatterjee-Kishore, Senior Vice President and Head of Immuno-Oncology Development at Astellas, highlighted the significance of this milestone. “The approval of zolbetuximab in China reinforces our dedication to delivering precision medicine solutions. By targeting CLDN18.2, we are addressing a critical unmet need in oncology, offering hope to patients and families affected by advanced gastric cancer,” she said.
The approval is also expected to have a positive financial impact, with the anticipated revenue already reflected in Astellas’ financial forecast for the fiscal year ending March 31, 2025. This development positions Astellas as a leader in precision oncology, enhancing its portfolio and strengthening its market presence in China and beyond.
Broader Implications for Gastric Cancer Treatment
Zolbetuximab’s approval represents a paradigm shift in the treatment of gastric cancer. By leveraging biomarker-driven strategies, it sets a new standard for precision medicine in oncology. This approach could pave the way for further advancements in the treatment of other biomarker-defined cancers, offering hope to patients who currently have limited options.
