Zolbetuximab + CAPOX in 1L claudin-18.2+(CLDN18.2+)/HER2-locally advanced (LA) or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma: Primary phase 3 results from GLOW.

초록

Background: There is an unmet need for novel targeted therapies that improve outcomes for pts with HER22 LA unresectable or mG/GEJ adenocarcinoma. CLDN18.2 is expressed in normal gastric mucosa cells and retained in most G/GEJ adenocarcinomas. In the phase 3 SPOTLIGHT study, zolbetuximab, a CLDN18.2-targeted chimeric monoclonal antibody, significantly prolonged PFS and OS in pts with CLDN18.2+/HER22 LA unresectable or mG/GEJ adenocarcinoma when combined with mFOLFOX6. GLOW (NCT03653507) is a phase 3 global, doubleblind study comparing zolbetuximab or PBO with capecitabine and oxaliplatin (CAPOX) as 1L treatment for this pt population. Methods: Pts with CLDN18.2+ (moderate-to-strong membranous CLDN18 staining in $75$3 TEAEs (72.8% vs 69.9%), and drug-related TEAEs leading to death (2.4% vs 2.8%) were similar in both arms. Conclusions: Targeting CLDN18.2 with zolbetuximab combined with CAPOX significantly prolonged PFS and OS in 1L pts with CLDN18.2+/HER22 LA unresectable or mG/GEJ adenocarcinoma. These results align with those observed in SPOTLIGHT and establish zolbetuximab + chemotherapy as a potential new standard-of-care option for these pts. Clinical trial information: NCT03653507. Research Sponsor: Astellas Pharma Inc.