Zolbetuximab: A Breakthrough in Treating Gastric/GEJ Cancer

Zolbetuximab Scores FDA Approval in CLDN 18.2+ Gastric/GEJ Cancer

The FDA has granted approval for zolbetuximab for the first-line treatment of patients with locally advanced unresectable or metastatic, HER2-negative, CLDN 18.2-positive gastric/GEJ cancer, making it the initial CLDN 18.2-targeted therapy in this patient cohort ¹.

Approval Process and Studies

The approval of zolbetuximab follows a Complete Response Letter (CRL) issued in January 2024 due to third-party manufacturing deficiencies identified during the prelicense inspection of the facility. Despite this, no concerns were raised regarding the clinical data of zolbetuximab, and no additional studies were requested to support the Biologics License Application (BLA).

This approval is backed by data from the phase 3 SPOTLIGHT (NCT03504397) and GLOW (NCT03653507) studies. In the SPOTLIGHT trial, the combination of zolbetuximab with 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) resulted in a median progression-free survival (PFS) of 10.61 months vs 8.67 months with placebo/mFOLFOX6, showing a 25% reduction in the risk of disease progression or death. The GLOW study, where zolbetuximab was combined with capecitabine and oxaliplatin (CAPOX), demonstrated a median PFS of 8.21 months compared to 6.80 months with placebo/CAPOX ^2,3.

Study Details

The international, double-blind, placebo-controlled SPOTLIGHT trial enrolled patients with previously untreated locally advanced unresectable or metastatic gastric/GEJ adenocarcinoma and CLDN18.2 positivity. Patients eligible for enrollment had moderate-to-strong CLDN18 staining in at least 75% of tumor cells, HER2-negative disease, and an ECOG performance status of 0 or 1.

In GLOW, a global, multicenter, double-blind, randomized study, patients in the experimental arm received zolbetuximab with a loading dose followed by a lower dose during subsequent cycles every 3 weeks, along with CAPOX, until confirmed disease progression or completion of 8 treatments ³.

The promising results of zolbetuximab in these studies highlight its potential as a targeted therapy for CLDN 18.2+ gastric/GEJ cancer, providing new hope for patients in this challenging disease setting.