FDA Approves Zolbetuximab Regimen for Locally Advanced, Unresectable Gastric/GEJ Adenocarcinoma

The FDA approved zolbetuximab-clzb (Vyloy) plus fluoropyrimidine- and platinum-containing chemotherapy for the treatment of patients with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are CLDN18.2 positive and have not previously been treated.¹

The approval is based off findings from the randomized phase 3 SPOTLIGHT (NCT03504397) and GLOW (NCT03653507) trials, which showed that the zolbetuximab regimen led to statistically significant improvements in progression-free survival (PFS) and overall survival (OS) compared with standard of care.

Per the SPOTLIGHT trial, median PFS was 10.61 months (95% CI, 8.9-12.5) with the zolbetuximab regimen, compared with 8.67 months (95% CI, 8.2-10.3) in those who received placebo plus mFOLFOX (HR, 0.751; 95% CI, 0.598-0.942; 1-sided P-value = .0066). Median OS was 18.23 months (95% CI, 16.4-22.9) and 15.54 months (95% CI, 13.5-16.5), respectively (HR, 0.750; 95% CI, 0.601-0.936; 1-sided P-value = .0053).

Similarly, data from the GLOW trial showed that the median PFS was 8.21 months (95% CI, 7.5-8.8) in the zolbetuximab group, compared with 6.8 months (95% CI, 6.1-8.1) in a group of patients who received CAPOX (HR, 0.687; [95% CI, 0.544-0.866]; 1-sided P-value = .0007). Median OS was 14.39 months (95% CI, 12.3-16.5) vs 12.16 months (95% CI, 10.3-13.7), respectively (HR 0.771; 95% CI, 0.615-0.965; 1-sided P-value = .0118).

In both trials, treatment-related adverse events (TRAEs) were similar between the 2 treatment groups. The most common all-grade TRAEs in the SPOTLIGHT trial were vomiting, nausea, neutropenia, febrile neutropenia, diarrhea, intestinal obstruction, pyrexia, pneumonia, respiratory failure, pulmonary embolism, decreased appetite, and sepsis. For the GLOW trial, common TRAEs were vomiting, nausea, decreased appetite, decreased platelet count, upper gastrointestinal hemorrhage, diarrhea, pneumonia, pulmonary embolism, and pyrexia.^2-3

References

1. FDA approves zolbetuximab-clzb with chemotherapy for gastric or gastroesophageal junction adenocarcinoma. FDA. Oct. 18, 2024. Accessed Oct. 18, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-zolbetuximab-clzb-chemotherapy-gastric-or-gastroesophageal-junction-adenocarcinoma?utm_medium=email&utm_source=govdelivery

2. Shitara K, et al. Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial. Lancet. 2023;401(10389):1655-1668.

3. Shah MA, et al. Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial. Nat Med. 2023;29(8):2133-2141.