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
Date | Setting/event | Relevant trial |
---|---|---|
Sep 2017 | 3rd-line PD-L1 +ve (≥1%), accelerated US approval | Keynote-059 |
Dec 2017 | 2nd-line PD-L1 +ve (≥1%), failed for OS | Keynote-061 |
Apr 2019 | 1st-line PD-L1 +ve, inconclusive | Keynote-062 |
May 2021 | 1st-line Her2 +ve, accelerated US approval for Herceptin combo | Keynote-811 |
Jul 2021 | 3rd-line accelerated US approval withdrawn | Keynote-061 & 062 |
Jun 2023 | 1st-line Her2 +ve, US label for Herceptin combo being narrowed to PD-L1 +ve (≥1%) | Keynote-811 |
Jun 2023 | Neoadj (chemo combo)/adjuvant, failed for EFS | Keynote-585 |
Dec 2023 | 1st-line (Her2 -ve? PD-L1 +ve?), Pdufa date for chemo combo | Keynote-859 |
Source: company statements.
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