The U.S. Food and Drug Administration (FDA) has granted approval to zolbetuximab (CLDN18.2 targeting antibody) for the treatment of patients with HER2-negative, CLDN18.2-positive locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. Zolbetuximab is to be used in combination with chemotherapy.
The approval is based on data from two pivotal Phase 3 trials, SPOTLIGHT and GLOW. These trials evaluated zolbetuximab in combination with chemotherapy compared to chemotherapy alone in patients with CLDN18.2-positive gastric and GEJ cancers.
SPOTLIGHT Trial
The SPOTLIGHT trial investigated zolbetuximab plus CAPOX (capecitabine and oxaliplatin) versus placebo plus CAPOX as first-line treatment. The study met its primary endpoint of progression-free survival (PFS), demonstrating a statistically significant improvement in the zolbetuximab arm. Secondary endpoints, including overall survival (OS), also showed a statistically significant benefit.
GLOW Trial
The GLOW trial evaluated zolbetuximab plus CAPOX versus placebo plus CAPOX as first-line treatment. The study met its primary endpoint of progression-free survival (PFS), demonstrating a statistically significant improvement in the zolbetuximab arm. Secondary endpoints, including overall survival (OS), also showed a statistically significant benefit.
Zolbetuximab is a first-in-class monoclonal antibody that targets CLDN18.2, a protein expressed in gastric and GEJ cancer cells but not in normal tissues. By binding to CLDN18.2, zolbetuximab induces antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), leading to cancer cell death.
This approval represents a significant advancement in the treatment of gastric and GEJ cancers, providing a new targeted therapy option for patients with CLDN18.2-positive tumors. The combination of zolbetuximab with chemotherapy offers improved outcomes compared to chemotherapy alone, addressing a critical unmet need in this patient population.
