Zolbetuximab-clzb Receives FDA Approval for Treatment of Advanced Gastric and GEJ Adenocarcinoma
Zolbetuximab-clzb (Vyloy; Astellas Pharma Inc) was granted FDA approval for the treatment of patients with locally advanced unresectable or metastatic human epidermal growth factor receptor 2-negative (HER2–) gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are claudin (CLDN) 18.2 positive. The decision is based on results from the phase 3 SPOTLIGHT (NCT03504397) and GLOW (NCT03462719) trials which both met their primary end point of progression-free survival.
According to the American Cancer Society, there will be approximately 27,000 new stomach cancer diagnosis in 2024. Gastric and gastroesophageal junction (GEJ) adenocarcinomas make up about 90% to 95% of all stomach cancers that develop from gland cells in the mucosa of the stomach. Patients with locally advanced, metastatic, or HER2– negative disease typically have worse outcomes.
Zolbetuximab-clzb is a cytolytic antibody that targets CLDN18.2, a novel therapeutic target in gastrointestinal malignancies, that affects nearly 38% of patients screened in the trials. CLDN18.2 positivity was defined as ≥75% of tumor cells showing moderate to strong membranous CLDN18 immunohistochemical staining, which was determined using the CLDN18 (43-14A) RxDx Assay (Ventana; Roche).
In the SPOTLIGHT trial, the researchers evaluated zolbetuximab-clzb in combination with oxaliplatin (Eloxatin; Sanofi-Aventus), leucovorin, and fluorouracil (Tolak; Hill Dermaceuticals Inc) (mFOLFOX6) compared with placebo and mFOLFOX6. The GLOW study investigated zolbetuximab-clzb plus capecitabine (Xeloda; Genetech) and oxaliplatin (CAPOX) compared with placebo and oxaliplatin. The trials had a primary end point of PFS and a secondary end point of overall survival, which were met in both. The most common treatment-emergent adverse events associated with zolbetuximab-clzb were nausea, vomiting, and decreased appetite.
The approval of zolbetuximab-clzb, based on the pivotal Phase 3 SPOTLIGHT and GLOW trials, brings forward a novel biomarker and new therapy for patients whose tumors are CLDN18.2 positive, and for those on the frontlines of treatment decision-making.
The FDA’s decision makes zolbetuximab-clzb the first and only CLDN18.2-targeted treatment for adults with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma.
