Second pivotal hit brings Claudin18.2 closer to approval

With confirmation of a hit in its second pivotal trial Astellas’s zolbetuximab appears set to become the industry’s first approved drug targeting Claudin18.2. Astellas said last night that the Glow trial had replicated the success of Spotlight, unveiled at January’s Asco-GI conference, in showing progression-free and overall survival benefit advantages when adding zolbetuximab on top of chemo. The first-line gastric/gastroesophageal junction (GEJ) cancer patients enrolled had to have Claudin18.2-positive tumours, amounting to around 39% of this population, and approval would require testing for this antigen to become standard. Baseline characteristics likely account for the numerical PFS and OS differences between Spotlight and Glow, which used slightly different chemo regimens, but statistically both results hit significance and were in line with the phase 2 Fast study data. More concerning is the 66-69% rate of nausea and vomiting reported in Glow (Spotlight had seen 65-81% rates, including 16% at grade 3 or above). Other quirks of Spotlight included no activity in the subset of GEJ patients, and no benefit at all in terms of overall response rate; for Glow this detail will hopefully be revealed when the full data are presented at an Asco virtual plenary series this afternoon.

Zolbetuximab in Her2-ve, Claudin18.2+ve* gastric/GEJ adenocarcinoma
  Spotlight Glow
(Folfox combo) (Capox combo)
mPFS (primary endpoint) 10.6mth vs 8.7mth 8.2mth vs 6.8mth
Stats HR=0.75, p=0.0066 HR=0.69, p=0.0007
mOS (secondary endpoint) 18.2mth vs 15.5mth 14.4mth vs 12.2mth
Stats HR=0.75, p=0.0053 HR=0.77, p=0.0118
ORR (secondary endpoint) 60.7% vs 62.1% TBC
Note: *defined as moderate-to-strong membrane staining in ≥75% of tumour cells by IHC. Source: Asco.

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