The FDA has granted approval to zolbetuximab (Vyloy), a first-in-class drug developed by Astellas, for the treatment of advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma in adults whose tumors exhibit claudin 18.2 (CLDN18.2) positivity. This approval marks a significant advancement in the treatment landscape for this aggressive cancer, addressing a critical unmet need for patients with limited therapeutic options. Zolbetuximab is intended for use in conjunction with fluoropyrimidine- and platinum-based chemotherapy.
The approval was based on the outcomes of two international Phase III clinical trials, involving 567 and 507 patients, respectively. These trials evaluated the efficacy of zolbetuximab in combination with different chemotherapy regimens. The results consistently demonstrated a statistically significant improvement in both progression-free survival and overall survival compared to chemotherapy alone.
Clinical Trial Efficacy
In one trial, patients receiving zolbetuximab plus chemotherapy experienced a median progression-free survival of 10.6 months, compared to 8.7 months in those receiving chemotherapy alone. Furthermore, the addition of zolbetuximab led to an approximate three-month improvement in overall survival. The second trial yielded similar results, with patients on zolbetuximab plus chemotherapy achieving a median progression-free survival of 8.2 months versus 6.8 months with chemotherapy alone, and an overall survival benefit of approximately two months.
Samuel J. Klempner, MD, a cancer specialist at Massachusetts General Hospital and associate professor at Harvard Medical School, emphasized the importance of this approval, stating that it "brings forward a novel biomarker and new therapy for patients whose tumors are CLDN18.2 positive." He noted the "tremendous unmet need" that remains despite recent advances in first-line treatment for these cancers.
Patient Selection and Biomarker Testing
Zolbetuximab is indicated for patients with HER2-negative gastric or GEJ adenocarcinoma that is either metastatic or unresectable. Notably, clinical trials indicated that approximately 38% of these patients have CLDN18.2-positive tumors. To ensure appropriate patient selection, the FDA also approved the VENTANA CLDN18 (43-14A) RxDx Assay, a diagnostic test designed to detect CLDN18.2-positive tumors and confirm patient eligibility for zolbetuximab treatment.
Safety Profile and Warnings
The most common side effects observed in clinical trials included nausea, vomiting, reduced appetite, diarrhea, pneumonia, and fever. Astellas, the drug's manufacturer, has issued warnings regarding the potential for serious allergic reactions and infusion-related reactions. Additionally, women are advised to avoid breastfeeding during zolbetuximab treatment and for eight months following the final dose.
