VYLOY (zolbetuximab) - Gastric or gastro-oesophageal junction (GEJ) adenocarcinoma

The Committee deems that the clinical benefit of VYLOY (zolbetuximab) 100 mg powder for concentrate for solution for infusion is substantial in the MA indication.

Considering, on the one hand:

• evidence in two double-blind, phase 3 studies of a superiority of VYLOY (zolbetuximab) in combination with dual fluoropyrimidine- and platinum-based chemotherapy compared with dual chemotherapy alone, in the ITT population in terms of:
  • overall survival: HR=0.784; CI95% [0.644; 0.954] (SPOTLIGHT study) and HR=0.763; CI95% [0.622; 0.936] (GLOW study);
  • progression-free survival: HR= 751; CI95% [0.598; 0.942] (SPOTLIGHT study) and HR= 0.687; CI95% [0.544; 0.866] (GLOW study);

but, on the other hand:

• methodological limitations concerning the analysis of the time to confirmed deterioration (TTCD) with non-demonstration of non-inferiority in the SPOTLIGHT study and a non-inferiority only for the physical function scale (first endpoint in the ranked sequence) in the GLOW study despite a ranked analysis scheduled in the protocols of the two studies;
• an effect size judged to be modest in terms of progression-free survival and overall survival,
• its safety profile marked, in particular, by an increase in nausea and vomiting,
• the problem of the transposability of the results to the French population (around 30% Asian patients in the SPOTLIGHT study and 60% in the GLOW study);

the Committee considers that VYLOY (zolbetuximab) 100 mg powder for concentrate for solution for infusion provides a minor clinical added value (CAV IV) compared to fluoropyrimidine- and platinum-based chemotherapy in the first-line treatment of adult patients with locally advanced unresectable or metastatic HER2-negative gastric or gastro-osophageal junction (GEJ) adenocarcinoma whose tumours are Claudin (CLDN) 18.2 positive.