How effective is Vyloy (zolbetuximab-clzb)?

Vyloy (zolbetuximab-clzb) is indicated in combination with fluoropyrimidine- and platinum-containing chemotherapy regimens for the first-line treatment of adults with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative adenocarcinoma of the stomach or gastroesophageal junction whose tumors are positive for tight junction protein 18.2 (CLDN18.2) as determined by an FDA-approved test.

Efficacy was evaluated in trialsSPOTLIGHT (NCT03504397) and GLOW (NCT03653507). Both trials were randomized (1:1), double-blind, multicenter trials, enrolling patients with CLDN18.2-positive advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma. The primary efficacy outcome measure in both trials was progression-free survival (PFS), as assessed by an independent review committee according to RECIST v1.1. Overall survival (OS) was an additional efficacy outcome measure.

InSPOTLIGHT, 565 patients were randomized to receive either Vyloy plus mFOLFOX6 chemotherapy or placebo plus mFOLFOX6 chemotherapy. Median PFS was 10.6 months (95% confidence interval [CI]: 8.9-12.5) in the Vyloy/chemotherapy group and 8.7 months (95% CI: 8.2- 10.3) (hazard ratio [HR] 0.751; 95% CI:0.598-0.942]; one-sided p value=0.0066). The median OS were 18.2 months (95%CI: 16.4-22.9) and 15.5 months, (95%CI: 3.5-16.5) respectively (HR 0.750; 95%CI: 0.601, 0.936; one-sided p value=0.0053).

InGLOW, 507 patients were randomized to receive Vyloy plus CAPOX chemotherapy or placebo plus CAPOX chemotherapy. Median PFS was 8.2 months (95%CI: 7.5-8.8) in the Vyloy/chemotherapy group and 6.8 months (95%CI: 6.1-8.1) in the placebo/chemotherapy group (hazard ratio [HR] 0.687; 95%CI: 0.544-0.866; one-sided p-value=0.0007). The median OS were 14.4 months (95%CI: 12.3-16.5) and 12.2 months (95%CI: 10.3-13.7) respectively (HR0.771; 95%CI: 0.615-0.965; one-sided p value=0.0118).

The most common serious adverse reactions in the SPOTLIGHT trial (≥2%) are vomiting, nausea, neutropenia, febrile neutropenia, diarrhea, ileus, pyrexia, pneumonia, respiratory failure, pulmonary embolism, decreased appetite, and sepsis. The most common serious adverse reactions (≥2%) in the GLOW trial were vomiting, nausea, decreased appetite, decreased platelet count, upper gastrointestinal bleeding, diarrhea, pneumonia, pulmonary embolism, and pyrexia.