Merck’s struggles in gastric adenocarcinoma continue

The influence of Merck & Co’s Keytruda in gastric adenocarcinoma – a setting that paints an increasingly confusing picture for doctors prescribing PD-(L)1 drugs – has waned some more. Today the drug failed in the perioperative setting in Keynote-585, falling behind Bristol Myers Squibb’s rival Opdivo, which carries an adjuvant US label based on Checkmate-577. Keynote-585 might separately also have confirmed a third- line accelerated label for Keytruda, but that indication has already been pulled. More concerning is Keynote-811, a study backing accelerated approval of a first-line Keytruda/Herceptin/chemo combo in Her2-positive patients, which on Friday yielded a PFS benefit only in PD-L1 expressers; accordingly Merck is moving to restrict that US label. Interestingly, Opdivo has full US approval for a first-line chemo combo in all comers, even though its Checkmate-649 trial only tested Her2-negatives, though inthe EU the label is much narrower, stating that patients have to be Her2-negative and PD-L1 ≥5% expressing. Keytruda’s next US battleground is a first-line chemo combo, which has a 16 December Pdufa date; the corresponding Keynote-859 trial concerned Her2-negatives only, and showed no effect in PD-L1 non-expressers, so the FDA’s verdict will be interesting.

Table 1. Keytruda's struggles in gastric/gastroesophageal junction adenocarcinoma

Source: company statements.