The FDA has approved zolbetuximab-clzb (Vyloy, Astellas), a claudin 18.2 (CLDN18.2)-directed cytolytic antibody, with fluoropyrimidine- and platinum-containing chemotherapy, for the first-line treatment of adults with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are CLDN18.2-positive, as determined by an FDA-approved test.

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The FDA has also approved the VENTANA CLDN18 (43-14A) RxDx Assay (Ventana Medical Systems/Roche Diagnostics) as a companion diagnostic device to identify patients with gastric or GEJ adenocarcinoma who may be eligible for treatment with zolbetuximab.

Efficacy was evaluated in the trials SPOTLIGHT (ClinicalTrials.gov. Identifier: NCT03504397) and GLOW (ClinicalTrials.gov. Identifier: NCT03653507). Both were multicenter, randomized (1:1), double-blind trials that enrolled patients with CLDN18.2-positive, advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma. The major efficacy outcome measure in both trials was progression-free survival (PFS), as assessed per RECIST (Response Evaluation Criteria in Solid Tumors) v1.1 by an independent review committee. Overall survival (OS) was an additional efficacy outcome measure.

In SPOTLIGHT, 565 patients were randomized to receive mFOLFOX6 chemotherapy with either zolbetuximab-clzb or placebo. Median PFS was 10.6 months (95% CI, 8.9-12.5 months) in the zolbetuximab-clzb arm and 8.7 months (95% CI, 8.2-10.3 months) in the placebo arm (hazard ratio [HR], 0.751; 95% CI, 0.598-0.942; 1-sided P=0.0066). Median OS was 18.2 months (95% CI,16.4-22.9 months) and 15.5 months (95% CI, 13.5-16.5 months), respectively (HR, 0.750; 95% CI, 0.601-0.936; 1-sided P=0.0053).

In GLOW, 507 patients were randomized to receive CAPOX chemotherapy with either zolbetuximab-clzb or placebo. Median PFS was 8.2 months (95% CI, 7.5-8.8 months) in the zolbetuximab-clzb arm and 6.8 months (95% CI, 6.1-8.1 months) in the placebo arm (HR, 0.687; 95% CI, 0.544- 0.866; 1-sided P=0.0007). Median OS was 14.4 months (95% CI, 12.3-16.5 months) and 12.2 months (95% CI, 10.3-13.7 months), respectively (HR, 0.771; 95% CI, 0.615-0.965; 1-sided P=0.0118).

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

The full prescribing information for zolbetuximab-clzb is posted here.

 
—GEN News Staff

Based on a press release from the FDA.