Vyloy (zolbetuximab-clzb)

Zolbetuximab plus chemotherapy was administered to real-world patients with CLDN18.2-positive AGC with acceptable safety profiles and showed preliminary antitumor efficacy. Nevertheless, some adverse events warrant careful monitoring.

These observations suggest that gastric wall changes detectable using US are closely linked to nausea and may reflect underlying gastric injury. This report also highlights the potential of bedside US monitoring to help predict and prevent nausea during zolbetuximab therapy.

The patient was treated with six cycles of zolbetuximab-CAPOX (zolbetuximab, capecitabine, and oxaliplatin), resulting in complete regression of liver metastases and significant tumor shrinkage. Additionally, transient treatment-related gastritis observed during therapy raises questions about the effects of CLDN18.2 inhibition on gastric mucosal integrity. Further research is warranted to refine patient selection for CLDN18.2-targeted therapy and investigate its broader physiological effects.

Patients were randomized 1:1 to receive zolbetuximab plus chemotherapy or placebo plus chemotherapy (mFOLFOX6 [modified folinic acid, 5-fluorouracil, and oxaliplatin] or CAPOX [capecitabine and oxaliplatin]). Zolbetuximab plus chemotherapy demonstrated favorable PFS and OS versus placebo plus chemotherapy in the Korean subgroup, with numerically greater efficacy compared with the overall pooled population. This may be potentially attributable to low rates of zolbetuximab discontinuation and toxicity management.

Finally, we identify current limitations in the field, including inconsistent CLDN18.2 testing criteria, and outline prioritized future directions to optimize integration of CLDN18.2-directed therapies across gastrointestinal cancers. By looking beyond zolbetuximab and incorporating cross-platform comparison, immuno-oncology considerations, and multi-tumor context, this review provides a broad and forward-looking framework to guide clinical application and next-generation research in CLDN18.2-targeted therapy.

Zolbetuximab is associated with high rates of nausea and vomiting during the initial infusion, whereas ICIs are associated with risk of later-onset immune-related toxicities that can be fatal in rare cases. In considering the available evidence, our opinion is that zolbetuximab is a reasonable option for initial targeted treatment in HER2-/CLDN18.2-positive advanced G/GEJ when PD-L1 CPS score is <10 based on the reliability of biomarker testing, comparable OS, and avoidance of potentially irreversible ICI-induced immune toxicity.

Clinicians should monitor albumin levels during treatment and consider nutritional support when indicated. These findings provide important insights for optimizing patient management and ensuring safe conversion surgery planning.

Serial PET imaging with 89Zr-labeled zolbetuximab, an anti-CLDN18.2 monoclonal antibody ([89Zr]Zr-DFO-zolbetuximab), and human IgG ([89Zr]Zr-DFO-IgG) as control (5.5-7.4 MBq) was performed 1, 3, and 6 d after injection, followed by ex vivo analysis of biodistribution... CLDN18.2 could serve as a promising biomarker for precise quantitative imaging and effective treatment of GCa and PDAC. This proof-of-concept study encourages the clinical translation of CLDN18.2 as a radiotheranostic in patients with CLDN18.2-expressing tumors.

Treatment was started with zolbetuximab plus 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX), which is typically used for CLDN18.2-positive gastric cancer, resulting in a partial response. This is the first case of zolbetuximab-based therapy applied to adenocarcinoma from a Meckel's diverticulum with a gastric phenotype due to a biomarker profile of gastric cancer. This case highlights the importance of identifying both the biomarker profile and tissue of origin of the tumor.

P1, N=12, Active, not recruiting, Astellas Pharma Global Development, Inc. | Recruiting --> Active, not recruiting

This review examines the mechanisms, safety profiles, and clinical trial outcomes of three targeted agents-bemarituzumab, zolbetuximab, and ramucirumab-which inhibit tumor growth through the FGFR2b, CLDN18.2, and VEGFR2 pathways, respectively. We also compare traditional versus adaptive clinical trial designs, explore emerging challenges such as therapeutic resistance and treatment-related toxicities, and consider implications for personalized medicine. Collectively, these agents represent a paradigm shift from empiric chemotherapy toward biomarker-driven immunotherapy, with the potential to significantly improve survival and quality of life in patients with advanced G/GEJ cancers.