Expanding therapeutic options targeting claudin-18.2

Abstract

Therapeutic options for patients with advanced gastric or gastro-oesophageal junction adenocarcinomas are rapidly evolving.¹ Although chemotherapy alone results in a median survival of less than a year, the majority (approximately 75%) of gastric and gastro-oesophageal junction adenocarcinoma tumours express molecular targets that are amenable to personalised antibody-based therapies.² These targeted treatments, if combined with cytotoxic chemotherapy, extend overall survival. Established monoclonal antibody targets include HER2 (also known as ERBB2) and PD-L1, with claudin-18.2 (CLD18.2) emerging as an addition within the past year. Zolbetuximab, a first-in-class monoclonal antibody targeting CLD18.2, improved overall survival when added to platinum-fluoropyrimidine chemotherapy in patients with CLD18.2-positive, advanced, untreated gastric or gastro-oesophageal junction adenocarcinoma.³ The positive results of SPOTLIGHT and GLOW validate CLD18.2 as a therapeutic target and established a basis for an expansive pipeline of next-generation CLD18.2-directed therapies.4, 5